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  • 1.
    Ashammakhi, Nureddin
    et al.
    Institute for Quantitative Health Science and Engineering (IQ) and Department of Biomedical Engineering (BME); Department of Microbiology and Molecular Genetics Michigan State University East Lansing MI.
    Nasiri, Rohollah
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Contag, Christopher H.
    Institute for Quantitative Health Science and Engineering (IQ) and Department of Biomedical Engineering (BME); Department of Microbiology and Molecular Genetics Michigan State University East Lansing MI.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Modelling Brain in a Chip2023In: The Journal of Craniofacial Surgery, ISSN 1049-2275, E-ISSN 1536-3732, Vol. 34, no 3, p. 845-847Article in journal (Other academic)
  • 2.
    Buchmann, Sebastian
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Enrico, Alessandro
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Holzreuter, Muriel Alexandra
    Reid, Michael S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Zeglio, Erica
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Defined neuronal-astrocytic interactions enabled with a 3D printed platformManuscript (preprint) (Other academic)
  • 3.
    Buchmann, Sebastian
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Enrico, Alessandro
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Holzreuter, Muriel Alexandra
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Reid, Michael S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Zeglio, Erica
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Probabilistic cell seeding and non-autofluorescent 3D-printed structures as scalable approach for multi-level co-culture modeling2023In: Materials Today Bio, ISSN 2590-0064, Vol. 21, p. 100706-100706, article id 100706Article in journal (Refereed)
    Abstract [en]

    To model complex biological tissue in vitro, a specific layout for the position and numbers of each cell type isnecessary. Establishing such a layout requires manual cell placement in three dimensions (3D) with micrometricprecision, which is complicated and time-consuming. Moreover, 3D printed materials used in compartmentalizedmicrofluidic models are opaque or autofluorescent, hindering parallel optical readout and forcing serial charac-terization methods, such as patch-clamp probing. To address these limitations, we introduce a multi-level co-culture model realized using a parallel cell seeding strategy of human neurons and astrocytes on 3D structuresprinted with a commercially available non-autofluorescent resin at micrometer resolution. Using a two-stepstrategy based on probabilistic cell seeding, we demonstrate a human neuronal monoculture that forms net-works on the 3D printed structure and can establish cell-projection contacts with an astrocytic-neuronal co-cultureseeded on the glass substrate. The transparent and non-autofluorescent printed platform allows fluorescence-based immunocytochemistry and calcium imaging. This approach provides facile multi-level compartmentaliza-tion of different cell types and routes for pre-designed cell projection contacts, instrumental in studying complextissue, such as the human brain.

  • 4.
    Buchmann, Sebastian
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden/ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Stoop, Pepijn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden/ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Roekevisch, Kim
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden/ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Jain, Saumey
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Kroon, Renee
    Department of Science and Technology, Laboratory of Organic Electronics, Linköping University, Norrköping, Sweden.
    Müller, Christian
    Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Hamedi, Mahiar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Zeglio, Erica
    AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden/ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden/ Wallenberg Initiative Materials Science for Sustainability, Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden/ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    In situ functionalization of polar polythiophene based organic electrochemical transistor to interface in vitro modelsManuscript (preprint) (Other academic)
  • 5.
    Chen, Chao
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Enrico, Alessandro
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center.
    Ek, Monica
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institute, Stockholm, 17177, Sweden.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Wågberg, Lars
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center.
    Bactericidal surfaces prepared by femtosecond laser patterning andlayer-by-layer polyelectrolyte coating2020In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 575, p. 286-297Article in journal (Refereed)
    Abstract [en]

    Antimicrobial surfaces are important in medical, clinical, and industrial applications, where bacterial infection and biofouling may constitute a serious threat to human health. Conventional approaches against bacteria involve coating the surface with antibiotics, cytotoxic polymers, or metal particles. However, these types of functionalization have a limited lifetime and pose concerns in terms of leaching and degradation of the coating. Thus, there is a great interest in developing long-lasting and non-leaching bactericidal surfaces. To obtain a bactericidal surface, we combine micro and nanoscale patterning of borosilicate glass surfaces by ultrashort pulsed laser irradiation and a non-leaching layer-by-layer polyelectrolyte modification of the surface. The combination of surface structure and surface charge results in an enhanced bactericidal effect against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. The laser patterning and the layer-by-layer modification are environmentally friendly processes that are applicable to a wide variety of materials, which makes this method uniquely suited for fundamental studies of bacteria-surface interactions and paves the way for its applications in a variety of fields, such as in hygiene products and medical devices.

  • 6. Delsing, Louise
    et al.
    Donnes, Pierre
    Sanchez, Jost
    Clausen, Maryam
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Falk, Anna
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Brolen, Gabriella
    Zetterberg, Henrik
    Hicks, Ryan
    Synnergren, Jane
    Barrier properties and transcriptome expression in human iPSC‐derived models of the blood–brain barrier2018In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 36, no 12, p. 1816-1827Article in journal (Refereed)
    Abstract [en]

    Cell-based models of the blood-brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in coculture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our coculture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in coculture, including upregulation of tight junction proteins, such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF, and PI3K-Akt pathways upon coculture. Our data suggest that coculture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in coculture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.

  • 7.
    Delsing, Louise
    et al.
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Skövde, Syst Biol Res Ctr, Sch Biosci, Skövde, Sweden.;AstraZeneca, R&D, Discovery Sci, Discovery Biol, Mölndal, Sweden..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Dept Neurosci, AIMES, Stockholm, Sweden..
    Falk, Anna
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hicks, Ryan
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, Mölndal, Sweden..
    Synnergren, Jane
    Univ Skövde, Syst Biol Res Ctr, Sch Biosci, Skövde, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, London, England.;UK Dementia Res Inst UCL, London, England..
    Models of the blood-brain barrier using iPSC-derived cells2020In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 107, article id 103533Article, review/survey (Refereed)
    Abstract [en]

    The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of the brain-penetrating properties of novel drug molecules. Currently used in vitro models of the BBB include immortalized brain endothelial cell lines and primary brain endothelial cells of human and animal origin. Unfortunately, many cell lines and primary cells do not recreate physiological restriction of transport in vitro. Human-induced pluripotent stem cell (iPSC)-derived brain endothelial cells have proven a promising alternative source of brain endothelial-like cells that replicate tight cell layers with low paracellular permeability. Given the possibility to generate large amounts of human iPSC-derived brain endothelial cells they are a feasible alternative when modelling the BBB in vitro. iPSC-derived brain endothelial cells form tight cell layers in vitro and their barrier properties can be enhanced through co-culture with other cell types of the BBB. Currently, many different models of the BBB using iPSC-derived cells are under evaluation to study BBB formation, maintenance, disruption, drug transport and diseases affecting the BBB. This review summarizes important functions of the BBB and current efforts to create iPSC-derived BBB models in both static and dynamic conditions. In addition, it highlights key model requirements and remaining challenges for human iPSC-derived BBB models in vitro.

  • 8.
    Elhami Nik, Farzad
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Department of Electronics, Information and Bioengineering, Politecnico di Milano.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Department of Neuroscience, Karolinska Institute.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Low-Cost PVD Shadow Masks with Submillimeter Resolution from Laser-Cut Paper2020In: Micromachines, E-ISSN 2072-666X, Vol. 11, no 7, article id 676Article in journal (Refereed)
    Abstract [en]

    We characterize an affordable method of producing stencils for submillimeter physical vapor deposition (PVD) by using paper and a benchtop laser cutter. Patterning electrodes or similar features on top of organic or biological substrates is generally not possible using standard photolithography. Shadow masks, traditionally made of silicon-based membranes, circumvent the need for aggressive solvents but suffer from high costs. Here, we evaluate shadow masks fabricated by CO2 laser processing from quantitative filter papers. Such papers are stiff and dimensionally stable, resilient in handling, and cut without melting or redeposition. Using two exemplary interdigitated electrode designs, we quantify the line resolution achievable with both high-quality and standard lenses, as well as the positional accuracy across multiple length scales. Additionally, we assess the gap between such laser-cut paper masks and a substrate, and quantify feature reproduction onto polycarbonate membranes. We find that ~100 µm line widths are achievable independent of lens type and that average positional accuracy is better than ±100 µm at 4”-wafer scale. Although this falls well short of the micron-size features achievable with typical shadow masks, resolution in the tenths to tens of millimeters is entirely sufficient for applications from contact pads to electrochemical cells, allowing new functionalities on fragile materials.

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  • 9.
    Engdahl, Elin
    et al.
    Environmental Toxicology, Department of Organismal Biology, Uppsala University, 75236 Uppsala, Sweden.
    D. M. van Schijndel, Maarten
    Environmental Toxicology, Department of Organismal Biology, Uppsala University, 75236 Uppsala, Sweden.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Department of Neuroscience, Karolinska Institute, 17177 Solna, Sweden.
    Di Criscio, Michela
    Environmental Toxicology, Department of Organismal Biology, Uppsala University, 75236 Uppsala, Sweden.
    Ramsbottom, Kerry A.
    Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK ; Computational Biology Facility, Technology Directorate, University of Liverpool, Liverpool L69 3BX, UK.
    Rigden, Daniel J
    Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK ; Computational Biology Facility, Technology Directorate, University of Liverpool, Liverpool L69 3BX, UK.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Department of Neuroscience, Karolinska Institute, 17177 Solna, Sweden.
    Rüegg, Joëlle
    Environmental Toxicology, Department of Organismal Biology, Uppsala University, 75236 Uppsala, Sweden.
    Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 11, article id 5534Article in journal (Refereed)
    Abstract [en]

    The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA’s known impact on neurodevelopment.

  • 10.
    Enrico, Alessandro
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Synthetic Physiology lab, Department of Civil Engineering and Architecture, University of Pavia, Via Ferrata 3, Pavia, 27100 Italy.
    Buchmann, Sebastian
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES.
    De Ferrari, Fabio
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Lin, Yunfan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wang, Yazhou
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering Sun Yat‐sen University Guangzhou 510275 P. R. China.
    Yue, Wan
    Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education School of Materials Science and Engineering Sun Yat‐sen University Guangzhou 510275 P. R. China.
    Mårtensson, Gustaf
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Mycronic AB Nytorpsvägen 9 Täby 183 53 Sweden.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hamedi, Mahiar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES.
    Zeglio, Erica
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Wallenberg Initiative Materials Science for Sustainability, Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, 114 18 Sweden.
    Cleanroom‐Free Direct Laser Micropatterning of Polymers for Organic Electrochemical Transistors in Logic Circuits and Glucose Biosensors2024In: Advanced Science, E-ISSN 2198-3844Article in journal (Refereed)
    Abstract [en]

    Organic electrochemical transistors (OECTs) are promising devices for bioelectronics, such as biosensors. However, current cleanroom-based microfabrication of OECTs hinders fast prototyping and widespread adoption of this technology for low-volume, low-cost applications. To address this limitation, a versatile and scalable approach for ultrafast laser microfabrication of OECTs is herein reported, where a femtosecond laser to pattern insulating polymers (such as parylene C or polyimide) is first used, exposing the underlying metal electrodes serving as transistor terminals (source, drain, or gate). After the first patterning step, conducting polymers, such as poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), or semiconducting polymers, are spin-coated on the device surface. Another femtosecond laser patterning step subsequently defines the active polymer area contributing to the OECT performance by disconnecting the channel and gate from the surrounding spin-coated film. The effective OECT width can be defined with high resolution (down to 2 µm) in less than a second of exposure. Micropatterning the OECT channel area significantly improved the transistor switching performance in the case of PEDOT:PSS-based transistors, speeding up the devices by two orders of magnitude. The utility of this OECT manufacturing approach is demonstrated by fabricating complementary logic (inverters) and glucose biosensors, thereby showing its potential to accelerate OECT research.

  • 11.
    Enrico, Alessandro
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Östmans, Rebecca
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Sundaravadivel, Naveen
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Moutaux, Lucille
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Cordier, Aurélie
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    3D Microvascularized Tissue Models by Laser-Based Cavitation Molding of Collagen2022In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 34, no 11Article in journal (Refereed)
  • 12.
    Hamedi, Mahiar Max
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Dept Neurosci, Swedish Med Nanosci Ctr, S-17177 Stockholm, Sweden..
    Zhang, Fengling
    Linkoping Univ, Dept Phys Chem & Biol, SE-58183 Linkoping, Sweden..
    Pei, Qibing
    Univ Calif Los Angeles, Dept Mat Sci & Engn, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90095 USA..
    Organic Polymer Electronics - A Special Issue in Honor of Prof. Olle Inganas2019In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 31, no 22, article id 1901940Article in journal (Refereed)
  • 13.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Invited speaker Combining Stem Cell and Device Engineering for In vitro Models of Human Physiology2023In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 52, no SUPPL 1, p. S29-S29Article in journal (Other academic)
  • 14.
    Herland, Anna
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Maoz, B. M.
    Das, D.
    Somayaji, M. R.
    Prantil-Baun, R.
    Novak, R.
    Cronce, M.
    Huffstater, T.
    Jeanty, S. S. F.
    Ingram, M.
    Chalkiadaki, A.
    Benson Chou, D.
    Marquez, S.
    Delahanty, A.
    Jalili-Firoozinezhad, S.
    Milton, Y.
    Sontheimer-Phelps, A.
    Swenor, B.
    Levy, O.
    Parker, K. K.
    Przekwas, A.
    Ingber, Donald
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips2020In: Nature Biomedical Engineering, E-ISSN 2157-846X, Vol. 4, no 4, p. 421-436Article in journal (Refereed)
    Abstract [en]

    Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.

  • 15.
    Herland, Anna
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115 USA.
    Maoz, Ben M.
    FitzGerald, Edward A.
    Grevesse, Thomas
    Vidoudez, Charles
    Sheehy, Sean P.
    Budnik, Nikita
    Dauth, Stephanie
    Mannix, Robert
    Budnik, Bogdan
    Parker, Kevin Kit
    Ingber, Donald E.
    Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine2020In: ADVANCED BIOSYSTEMS, ISSN 2366-7478, Vol. 4, no 9, article id 1900230Article in journal (Refereed)
    Abstract [en]

    The functional state of the neurovascular unit (NVU), composed of the blood-brain barrier and the perivasculature that forms a dynamic interface between the blood and the central nervous system (CNS), plays a central role in the control of brain homeostasis and is strongly affected by CNS drugs. Human primary brain microvascular endothelium, astrocyte, pericyte, and neural cell cultures are often used to study NVU barrier functions as well as drug transport and efficacy; however, the proteomic and metabolomic responses of these different cell types are not well characterized. Culturing each cell type separately, using deep coverage proteomic analysis and characterization of the secreted metabolome, as well as measurements of mitochondrial activity, the responses of these cells under baseline conditions and when exposed to the NVU-impairing stimulant methamphetamine (Meth) are analyzed. These studies define the previously unknown metabolic and proteomic profiles of human brain pericytes and lead to improved characterization of the phenotype of each of the NVU cell types as well as cell-specific metabolic and proteomic responses to Meth.

  • 16.
    Herland, Anna
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Dept Neurosci, Ctr Adv Integrated Med & Engn Sci AIMES, S-17177 Stockholm, Sweden..
    Yoon, Myung-Han
    Gwangju Inst Sci & Technol, Sch Mat Sci & Engn, 123 Cheomdangwagi Ro, Gwangju 61005, South Korea..
    Macromolecular Bioelectronics2020In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 20, no 11, article id 2000329Article in journal (Other academic)
  • 17.
    Hernando, Sara
    et al.
    Karolinska Inst, Ctr Adv Integrated Med & Engn Sci AIMES, S-17177 Stockholm, Sweden.;KTH Royal Inst Technol, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.;Univ Basque Country, Sch Pharm, Lab Pharmaceut, NanoBioCel Res Grp,UPV EHU, Vitoria 01006, Spain.;Inst Hlth Carlos III, Biomed Res Networking Ctr Bioengn Biomat & Nanome, Madrid 28029, Spain.;NanoBioCel Res Grp, Bioaraba, Vitoria 01006, Spain..
    Nikolakopoulou, Polyxeni
    KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Ctr Adv Integrated Med & Engn Sci AIMES, S-17177 Stockholm, Sweden.; Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Ctr Adv Integrated Med & Engn Sci AIMES, S-17177 Stockholm, Sweden.; Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Hernandez, Rosa Maria
    Univ Basque Country, Sch Pharm, Lab Pharmaceut, NanoBioCel Res Grp,UPV EHU, Vitoria 01006, Spain.;Inst Hlth Carlos III, Biomed Res Networking Ctr Bioengn Biomat & Nanome, Madrid 28029, Spain.; NanoBioCel Res Grp, Bioaraba, Vitoria 01006, Spain...
    Igartua, Manoli
    Univ Basque Country, Sch Pharm, Lab Pharmaceut, NanoBioCel Res Grp,UPV EHU, Vitoria 01006, Spain.;Inst Hlth Carlos III, Biomed Res Networking Ctr Bioengn Biomat & Nanome, Madrid 28029, Spain.;NanoBioCel Res Grp, Bioaraba, Vitoria 01006, Spain...
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Dual effect of TAT functionalized DHAH lipid nanoparticles with neurotrophic factors in human BBB and microglia cultures2022In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, no 1, article id 22Article in journal (Refereed)
    Abstract [en]

    Background

    Neurodegenerative diseases (NDs) are an accelerating global health problem. Nevertheless, the stronghold of the brain- the blood–brain barrier (BBB) prevents drug penetrance and dwindles effective treatments. Therefore, it is crucial to identify Trojan horse-like drug carriers that can effectively cross the blood–brain barrier and reach the brain tissue. We have previously developed polyunsaturated fatty acids (PUFA)-based nanostructured lipid carriers (NLC), namely DHAH-NLC. These carriers are modulated with BBB-permeating compounds such as chitosan (CS) and trans-activating transcriptional activator (TAT) from HIV-1 that can entrap neurotrophic factors (NTF) serving as nanocarriers for NDs treatment. Moreover, microglia are suggested as a key causative factor of the undergoing neuroinflammation of NDs. In this work, we used in vitro models to investigate whether DHAH-NLCs can enter the brain via the BBB and investigate the therapeutic effect of NTF-containing DHAH-NLC and DHAH-NLC itself on lipopolysaccharide-challenged microglia.

    Methods

    We employed human induced pluripotent stem cell-derived brain microvascular endothelial cells (BMECs) to capitalize on the in vivo-like TEER of this BBB model and quantitatively assessed the permeability of DHAH-NLCs. We also used the HMC3 microglia cell line to assess the therapeutic effect of NTF-containing DHAH-NLC upon LPS challenge.

    Results

    TAT-functionalized DHAH-NLCs successfully crossed the in vitro BBB model, which exhibited high transendothelial electrical resistance (TEER) values (≈3000 Ω*cm2). Specifically, the TAT-functionalized DHAH-NLCs showed a permeability of up to 0.4% of the dose. Furthermore, using human microglia (HMC3), we demonstrate that DHAH-NLCs successfully counteracted the inflammatory response in our cultures after LPS challenge. Moreover, the encapsulation of glial cell-derived neurotrophic factor (GNDF)-containing DHAH-NLCs (DHAH-NLC-GNDF) activated the Nrf2/HO-1 pathway, suggesting the triggering of the endogenous anti-oxidative system present in microglia.

    Conclusions

    Overall, this work shows that the TAT-functionalized DHAH-NLCs can cross the BBB, modulate immune responses, and serve as cargo carriers for growth factors; thus, constituting an attractive and promising novel drug delivery approach for the transport of therapeutics through the BBB into the brain.

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  • 18.
    Iseri, Emre
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Gustafsson, Linnea
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hedhammar, My
    KTH, School of Biotechnology (BIO), Centres, Centre for Bioprocess Technology, CBioPT. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Heuchel, Rainer
    Karolinska Institute.
    Löhr, Matthias
    Karolinska Institute.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Wei, Xi
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems.
    Cell encapsulation in alginate filaments with spider silk coating for targeted drug deliveryManuscript (preprint) (Other academic)
  • 19. Jagadeesan, Srikanth
    et al.
    Workman, Michael J.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Svendsen, Clive N.
    Vatine, Gad D.
    Generation of a Human iPSC-Based Blood-Brain Barrier Chip2020In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 157, article id e60925Article in journal (Refereed)
    Abstract [en]

    The blood brain barrier (BBB) is formed by neurovascular units (NVUs) that shield the central nervous system (CNS) from a range of factors found in the blood that can disrupt delicate brain function. As such, the BBB is a major obstacle to the delivery of therapeutics to the CNS. Accumulating evidence suggests that the BBB plays a key role in the onset and progression of neurological diseases. Thus, there is a tremendous need for a BBB model that can predict penetration of CNS-targeted drugs as well as elucidate the BBB's role in health and disease. We have recently combined organ-on-chip and induced pluripotent stem cell (iPSC) technologies to generate a BBB chip fully personalized to humans. This novel platform displays cellular, molecular, and physiological properties that are suitable for the prediction of drug and molecule transport across the human BBB. Furthermore, using patient-specific BBB chips, we have generated models of neurological disease and demonstrated the potential for personalized predictive medicine applications. Provided here is a detailed protocol demonstrating how to generate iPSC-derived BBB chips, beginning with differentiation of iPSC-derived brain microvascular endothelial cells (iBMECs) and resulting in mixed neural cultures containing neural progenitors, differentiated neurons, and astrocytes. Also described is a procedure for seeding cells into the organ chip and culturing of the BBB chips under controlled laminar flow. Lastly, detailed descriptions of BBB chip analyses are provided, including paracellular permeability assays for assessing drug and molecule permeability as well as immunocytochemical methods for determining the composition of cell types within the chip.

  • 20.
    Jain, Saumey
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering. Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden; Division of Nanobiotechnology, Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden.
    Birgersson, Madeleine
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics.
    Kipen, Javier
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Jaldén, Joakim
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Raja, Shyamprasad Natarajan
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Williams, Cecilia
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Sensing of protein and DNA complexes using solid-state nanopores2023In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 122, no 3S1Article in journal (Refereed)
  • 21.
    Jain, Saumey
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Institutet Solna 171 65 Sweden.
    Thongkorn, Surangrat
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE) Department of Clinical Chemistry Faculty of Allied Health Sciences Chulalongkorn University Bangkok 10330 Thailand.
    Hesen, Rick
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hägg, Alice
    Neural Stem Cells Department of Experimental Medical Science Lund Stem Cell Center Lund University Lund 221 84 Sweden.
    Moslem, Mohsen
    Department of Neuroscience Karolinska Institutet Solna 171 65 Sweden.
    Falk, Anna
    Neural Stem Cells Department of Experimental Medical Science Lund Stem Cell Center Lund University Lund 221 84 Sweden;Department of Neuroscience Karolinska Institutet Solna 171 65 Sweden.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Neuroscience Karolinska Institutet Solna 171 65 Sweden;Department of Neuroscience Karolinska Institutet Solna 171 65 Sweden.
    On‐Chip Neural Induction Boosts Neural Stem Cell Commitment: Toward a Pipeline for iPSC‐Based Therapies2024In: Advanced Science, E-ISSN 2198-3844, article id advs.202401859Article in journal (Refereed)
    Abstract [en]

    The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.

    This study highlights the development of a microfluidic platform to reprogram somatic cells from donors into induced pluripotent stem cells and further differentiate them into neural stem cells. This confined microfluidic platform boosts neural stem cell generation commitment at an early stage, as denoted by the pathway enrichment analysis. image

  • 22.
    Jang, Kyung-Jin
    et al.
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Otieno, Monicah A.
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Ronxhi, Janey
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Lim, Heng-Keang
    Janssen Pharmaceut Res & Dev, Drug Metab & Pharmacokinet, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Ewart, Lorna
    AstraZeneca, Biopharmaceut Sci Unit, Clin Pharmacol & Safety Sci Dept, Cambridge CB4 0WG, England..
    Kodella, Konstantia R.
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Petropolis, Debora B.
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Kulkarni, Gauri
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Rubins, Jonathan E.
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA.;Jnana Therapeut, Boston, MA 02210 USA..
    Conegliano, David
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Nawroth, Janna
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Simic, Damir
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Lam, Wing
    Janssen Pharmaceut Res & Dev, Drug Metab & Pharmacokinet, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Singer, Monica
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Barale, Erio
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Singh, Bhanu
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Sonee, Manisha
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Streeter, Anthony J.
    Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Manthey, Carl
    Janssen Pharmaceut Res & Dev, IPD Biol, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
    Jones, Barry
    AstraZeneca, Biopharmaceut Sci Unit, Clin Pharmacol & Safety Sci Dept, Cambridge CB4 0WG, England..
    Srivastava, Abhishek
    AstraZeneca, Biopharmaceut Sci Unit, Clin Pharmacol & Safety Sci Dept, Cambridge CB4 0WG, England..
    Andersson, Linda C.
    AstraZeneca, Biopharmaceut Sci Unit, Clin Pharmacol & Safety Sci Dept, SE-43183 Gothenburg, Sweden..
    Williams, Dominic
    AstraZeneca, Biopharmaceut Sci Unit, Clin Pharmacol & Safety Sci Dept, Cambridge CB4 0WG, England..
    Park, Hyoungshin
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Barrile, Riccardo
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Sliz, Josiah
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Haney, Suzzette
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Karalis, Katia
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Ingber, Donald E.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02139 USA..
    Hamilton, Geraldine A.
    Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
    Reproducing human and cross-species drug toxicities using a Liver-Chip2019In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 11, no 517, article id eaax5516Article in journal (Refereed)
    Abstract [en]

    Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.

  • 23.
    Jury, Michael
    et al.
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Rasti Boroojeni, Fatemeh
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Ludwig, Saskia
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Civitelli, Livia
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden;Nuffield Department of Clinical Neurosciences John Radcliffe Hospital West Wing University of Oxford Oxford OX3 9DU UK.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Institute of Microtechnology Center of Pharmaceutical Engineering Technische Universität Braunschweig Braunschweig 38106 Germany.
    Selegård, Robert
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Center for Integrated Medical and Engineering Science Department of Neuroscience Karolinska Institute Solna 171 65 Sweden;Division of Nanobiotechnology Department of Protein Science, Science for Life Laboratory KTH Royal Institute of Technology Stockholm 17165 Sweden.
    Aili, Daniel
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Bioorthogonally Cross‐Linked Hyaluronan–Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication2022In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 11, no 11, article id 2102097Article in journal (Refereed)
    Abstract [en]

    Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons toward development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here a modular hydrogel system for neural 3D cell cultures, based on hyaluronan and poly(ethylene glycol), that is cross-linked and functionalized with human recombinant LN-521 using bioorthogonal copper-free click chemistry, is shown. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Long-term neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of bioprinted and syringe extruded lt-NES, which can facilitate biofabrication and development of cell-based therapies.

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  • 24.
    Kavand, Hanie
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nasiri, Rohollah
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES Center for the Advancement of Integrated Medical and Engineering Sciences Department of Neuroscience Karolinska Institute Stockholm Sweden.
    Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electro‐optical Interfaces2021In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, p. 2107876-2107876Article in journal (Refereed)
    Abstract [en]

    Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ-on-a-chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional two-dimensional cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real-time stimuli and readout capacity. The next technology leap in reproducing in vivo-like functionality and real-time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, we give an overview of multi-sensing for Body-on-Chip platforms. Finally, we give our perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.

  • 25.
    Kavand, Hanie
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Visa, Montse
    The Rolf Luft Research center for Diabetes and Endocrinology Karolinska Institutet Stockholm SE‐17176 Sweden.
    Köhler, Martin
    The Rolf Luft Research center for Diabetes and Endocrinology Karolinska Institutet Stockholm SE‐17176 Sweden.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Berggren, Per‐Olof
    The Rolf Luft Research center for Diabetes and Endocrinology Karolinska Institutet Stockholm SE‐17176 Sweden.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Division of Micro‐ and Nanosystems Department of Intelligent Systems KTH Royal Institute of Technology Malvinas Väg 10 pl 5 Stockholm SE‐10044 Sweden;Division of Nanobiotechnology Department of Protein Science KTH Royal Institute of Technology Tomtebodavägen 23a Stockholm SE‐17165 Sweden;AIMES Center for the Advancement of Integrated Medical and Engineering Sciences Department of Neuroscience Karolinska Institutet Solnavägen 9/B8 Stockholm SE‐17165 Sweden.
    3D‐Printed Biohybrid Microstructures Enable Transplantation and Vascularization of Microtissues in the Anterior Chamber of the Eye2023In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095Article in journal (Refereed)
    Abstract [en]

    Hybridizing biological cells with man-made sensors enable the detection of a wide range of weak physiological responses with high specificity. The anterior chamber of the eye (ACE) is an ideal transplantation site due to its ocular immune privilege and optical transparency, which enable superior non-invasive longitudinal analyses of cells and microtissues. Engraftment of biohybrid microstructures in the ACE might, however, be affected by the pupillary response and dynamics. Here, sutureless transplantation of biohybrid microstructures, 3D printed in IP-Visio photoresin, containing a precisely localized pancreatic islet to the ACE of mice is presented. The biohybrid microstructures allow mechanical fixation in the ACE, independent of iris dynamics. After transplantation, islets in the microstructures successfully sustain their functionality for over 20 weeks and become vascularized despite physical separation from the vessel source (iris) and immersion in a low-viscous liquid (aqueous humor) with continuous circulation and clearance. This approach opens new perspectives in biohybrid microtissue transplantation in the ACE, advancing monitoring of microtissue-host interactions, disease modeling, treatment outcomes, and vascularization in engineered tissues.

  • 26.
    Khaliliazar, Shirin
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Ouyang, Liangqi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Piper, Andrew
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Chondrogiannis, Georgios
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Hanze, Martin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hamedi, Mahiar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Electrochemical Detection of Genomic DNA Utilizing Recombinase Polymerase Amplification and Stem-Loop Probe2020In: ACS Omega, E-ISSN 2470-1343, Vol. 5, no 21, p. 12103-12109Article in journal (Refereed)
    Abstract [en]

    Nucleic acid tests integrated into digital point-of-care (POC) diagnostic systems have great potential for the future of health care. However, current methods of DNA amplification and detection require bulky and expensive equipment, many steps, and long process times, which complicate their integration into POC devices. We have combined an isothermal DNA amplification method, recombinase polymerase amplification, with an electrochemical stem-loop (S-L) probe DNA detection technique. By combining these methods, we have created a system that is able to specifically amplify and detect as few as 10 copies/mu L Staphylococcus epidermidis DNA with a total time to result of 70-75 min.

  • 27. Lundin, Anders
    et al.
    Delsing, Louise
    Clausen, Maryam
    Ricchiuto, Piero
    Sanchez, Jose
    Sabirsh, Alan
    Ding, Mei
    Synnergren, Jane
    Zetterberg, Henrik
    Brolen, Gabriella
    Hicks, Ryan
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Institutet, Sweden.
    Falk, Anna
    Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models2018In: Stem Cell Reports, ISSN 2213-6711, Vol. 10, no 3, p. 1030-1045Article in journal (Refereed)
    Abstract [en]

    In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells. We characterized NES-Astro and astrocytic models from primary sources, astrocytoma (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake, inflammatory competence, calcium signaling response, and APOE secretion. Finally, we assess modulation of astrocyte biology using APOE-annotated compounds, confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC-derived astrocytes. Our data show large diversity among astrocytic models and emphasize a cellular context when studying astrocyte biology.

  • 28.
    Lundin, Anders
    et al.
    AstraZeneca, Translat Genom, BioPharmaceut R&D, Discovery Sci, Pepparedsleden 1, S-43183 Mölndal, Sweden..
    Ricchiuto, Piero
    AstraZeneca, Discovery Sci R&D, Data Sci & Quantitat Biol, Darwin Bldg,310 Milton Rd, Cambridge CB4 0WG, England..
    Clausen, Maryam
    AstraZeneca, Translat Genom, BioPharmaceut R&D, Discovery Sci, Pepparedsleden 1, S-43183 Mölndal, Sweden..
    Hicks, Ryan
    AstraZeneca, Translat Genom, BioPharmaceut R&D, Discovery Sci, Pepparedsleden 1, S-43183 Mölndal, Sweden..
    Falk, Anna
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. ;Karolinska Inst, Ctr Adv Integrated Med & Engn Sci, AIMES, S-17177 Stockholm, Sweden..
    hiPS-Derived Astroglia Model Shows Temporal Transcriptomic Profile Related to Human Neural Development and Glia Competence Acquisition of a Maturing Astrocytic Identity2020In: Advanced Biosystems, ISSN 2366-7478, Vol. 4, no 5, article id 1900226Article in journal (Refereed)
    Abstract [en]

    Astrocyte biology has a functional and cellular diversity only observed in humans. The understanding of the regulatory network governing outer radial glia (RG), responsible for the expansion of the outer subventricular zone (oSVZ), and astrocyte cellular development remains elusive, partly since relevant human material to study these features is not readily available. A human-induced pluripotent stem cell derived astrocytic model, NES-Astro, has been recently developed, with high expression of astrocyte-associated markers and high astrocyte-relevant functionality. Here it is studied how the NES-Astro phenotype develops during specification and its correlation to known RG and astrocyte characteristics in human brain development. It is demonstrated that directed differentiation of neurogenic long-term neuroepithelial stem cells undergo a neurogenic-to-gliogenic competence preferential change, acquiring a glial fate. Temporal transcript profiles of long- and small RNA corroborate previously shown neurogenic restriction by glia-associated let-7 expression. Furthermore, NES-Astro differentiation displays proposed mechanistic features important for the evolutionary expansion of the oSVZ together with an astroglia/astrocyte transcriptome. The NES-Astro generation is a straight-forward differentiation protocol from stable and expandable neuroepithelial stem cell lines derived from iPS cells. Thus, the NES-Astro is an easy-access cell system with high biological relevance for studies of mechanistic traits of glia and astrocyte.

  • 29.
    Maoz, Ben M.
    et al.
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Tel Aviv Univ, Dept Biomed Engn, Fac Engn, Tel Aviv, Israel.;Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.;Tel Aviv Univ, Ctr Nanosci & Nanotechnol, Tel Aviv, Israel..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Karolinska Inst, Dept Neurosci, Swedish Med Nanosci Ctr, Stockholm, Sweden..
    FitzGerald, Edward A.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Grevesse, Thomas
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Vidoudez, Charles
    Harvard Univ, Small Mol Mass Spectrometry Facil, Cambridge, MA 02138 USA..
    Pacheco, Alan R.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.;Boston Univ, Biol Design Ctr, Boston, MA 02215 USA..
    Sheehy, Sean P.
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Park, Tae-Eun
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Dauth, Stephanie
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Mannix, Robert
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Budnik, Nikita
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA..
    Shores, Kevin
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Cho, Alexander
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Nawroth, Janna C.
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Segre, Daniel
    Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.;Boston Univ, Biol Design Ctr, Boston, MA 02215 USA.;Boston Univ, Dept Phys, Dept Biomed Engn, Dept Biol, 590 Commonwealth Ave, Boston, MA 02215 USA..
    Budnik, Bogdan
    Harvard Univ, Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA..
    Ingber, Donald E.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA..
    Parker, Kevin Kit
    Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells2018In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 36, no 9, p. 865-+Article in journal (Refereed)
    Abstract [en]

    The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.

  • 30.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AstraZeneca, CVRM Safety, Clin Pharmacol & Safety Sci, R&D, Gothenburg, Sweden..
    Jury, Michael
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Rasti Boroojeni, Fatemeh
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Ludwig, Saskia
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Holzreuter, Muriel
    Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden..
    Buchmann, Sebastian
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden.;KTH Royal Inst Technol, Dept Prot Sci, Div Nanobiotechnol, Sci Life Lab, Solna, Sweden..
    Aman Trager, Andrea
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Selegard, Robert
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Tech Univ Carolo Wilhelmina Braunschweig, Inst Microtechnol, Braunschweig, Germany.;Tech Univ Carolo Wilhelmina Braunschweig, Ctr Pharmaceut Engn, Braunschweig, Germany..
    Aili, Daniel
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden.;KTH Royal Inst Technol, Dept Prot Sci, Div Nanobiotechnol, Sci Life Lab, Solna, Sweden..
    Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels2023In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 24, no 1, article id 2165871Article in journal (Refereed)
    Abstract [en]

    Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood-brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system.

  • 31.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Jury, Michael
    Rasti Boroojeni, Fatemeh
    Ludwig, Saskia L.
    Holzreuter, Muriel
    Buchmann, Sebastian
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Selegård, Robert
    Winkler, Thomas E.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Aili, Daniel
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Astrocyte 3D Culture and Bioprinting using Peptide Functionalized Hyaluronan HydrogelsManuscript (preprint) (Other academic)
  • 32.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AstraZeneca, R&D, Clin Pharmacol & Safety Sci, CVRM Safety, S-43150 Gothenburg, Sweden..
    Nasiri, Rohollah
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Ctr Adv Integrated Med & Engn Sci, Dept Neurosci, AIMES, S-17177 Solna, Sweden..
    Orrego, Alessandra Tamashiro
    KTH. Sci Life Lab, S-17165 Solna, Sweden..
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Institute of Microtechnology Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Braunschweig, 38106, Germany.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. Department of Neuroscience, Karolinska Institute, 17177 Solna, Sweden..
    Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover2022In: Biosensors, ISSN 2079-6374, Vol. 12, no 10, p. 839-, article id 839Article in journal (Refereed)
    Abstract [en]

    Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the main observable metabolic actions of astrocytes. To gain insight into these processes, it is essential to establish scalable and functional sources for in vitro studies of astrocytes. In this study, we compared the metabolic turnover of glucose and lactate in astrocytes derived from human induced pluripotent stem cell (hiPSC)-derived Astrocytes (hiAstrocytes) as a scalable astrocyte source to human fetal astrocytes (HFAs). Using a user-friendly, commercial flow-based biosensor, we could verify that hiAstrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower. Specifically, under identical culture conditions in a defined media, HFAs have 2.3 times higher levels of lactate production compared to hiAstrocytes. In terms of glucose, HFAs have 2.1 times higher consumption levels than hiAstrocytes at 24 h. Still, as we describe their glycogenic phenotype, our study demonstrates the use of hiAstrocytes and flow-based biosensors for metabolic studies of astrocyte function.

  • 33.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nasiri, Rohollah
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Tamashiro Orrego, Alessandra
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Metabolic effects from ketone treatment – lactate and glucose turnover in astrocytesManuscript (preprint) (Other academic)
  • 34.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nikolakopoulou, Polyxeni
    AIMES, Center for Integrated Medical and Engineering Sciences Department of Neuroscience Karolinska Institute Solnavägen 9/B8 Solna 171 65 Sweden.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit2021In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 17, no 32, p. 2101785-Article in journal (Refereed)
    Abstract [en]

    Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. In this study, the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC-derived endothelial-like and astrocyte-like cells. Clear cellular disruption is observed when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.

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  • 35.
    McCuskey, Samantha R.
    et al.
    Natl Univ Singapore, Dept Chem, Singapore 119077, Singapore..
    Chatsirisupachai, Jirat
    Univ Calif Santa Barbara, Ctr Polymers & Organ Solids, Santa Barbara, CA 93106 USA.;Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.;Vidyasirimedhi Inst Sci & Technol, Sch Mol Sci & Engn, Dept Mat Sci & Engn, Rayong 21210, Thailand..
    Zeglio, Erica
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Parlak, Onur
    Karolinska Inst, Dept Med Solna, Dermatol & Venereol Div, S-17177 Stockholm, Sweden.;Karolinska Inst, AIMES Ctr Integrated Med & Engn Sci, Dept Neurosci, S-17177 Stockholm, Sweden..
    Panoy, Patchareepond
    Univ Calif Santa Barbara, Ctr Polymers & Organ Solids, Santa Barbara, CA 93106 USA.;Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.;Vidyasirimedhi Inst Sci & Technol, Sch Mol Sci & Engn, Dept Mat Sci & Engn, Rayong 21210, Thailand..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, AIMES Ctr Integrated Med & Engn Sci, Dept Neurosci, S-17177 Stockholm, Sweden..
    Bazan, Guillermo C.
    Natl Univ Singapore, Dept Chem, Singapore 119077, Singapore..
    Nguyen, Thuc-Quyen
    Current Progress of Interfacing Organic Semiconducting Materials with Bacteria2022In: Chemical Reviews, ISSN 0009-2665, E-ISSN 1520-6890, Vol. 122, no 4, p. 4791-4825Article, review/survey (Refereed)
    Abstract [en]

    Microbial bioelectronics require interfacing microorganisms with electrodes. The resulting abiotic/biotic platforms provide the basis of a range of technologies, including energy conversion and diagnostic assays. Organic semiconductors (OSCs) provide a unique strategy to modulate the interfaces between microbial systems and external electrodes, thereby improving the performance of these incipient technologies. In this review, we explore recent progress in the field on how OSCs, and related materials capable of charge transport, are being used within the context of microbial systems, and more specifically bacteria. We begin by examining the electrochemical communication modes in bacteria and the biological basis for charge transport. Different types of synthetic organic materials that have been designed and synthesized for interfacing and interrogating bacteria are discussed next, followed by the most commonly used characterization techniques for evaluating transport in microbial, synthetic, and hybrid systems. A range of applications is subsequently examined, including biological sensors and energy conversion systems. The review concludes by summarizing what has been accomplished so far and suggests future design approaches for OSC bioelectronics materials and technologies that hybridize characteristic properties of microbial and OSC systems.

  • 36. Nikolakopoulou, Polyxeni
    et al.
    Rauti, Rossana
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Shlomy, Iftach
    Maoz, Ben M.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Center for the Advancement of Integrated Medical and Engineering Sciences, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Recent progress in translational engineered in vitro models of the central nervous system2020In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 143, no 11, p. 3181-3213Article in journal (Refereed)
    Abstract [en]

    The complexity of the human brain poses a substantial challenge for the development of models of the CNS. Current animal models lack many essential human characteristics (in addition to raising operational challenges and ethical concerns), and conventional in vitro models, in turn, are limited in their capacity to provide information regarding many functional and systemic responses. Indeed, these challenges may underlie the notoriously low success rates of CNS drug development efforts. During the past 5 years, there has been a leap in the complexity and functionality of in vitro systems of the CNS, which have the potential to overcome many of the limitations of traditional model systems. The availability of human-derived induced pluripotent stem cell technology has further increased the translational potential of these systems. Yet, the adoption of state-of-the-art in vitro platforms within the CNS research community is limited. This may be attributable to the high costs or the immaturity of the systems. Nevertheless, the costs of fabrication have decreased, and there are tremendous ongoing efforts to improve the quality of cell differentiation. Herein, we aim to raise awareness of the capabilities and accessibility of advanced in vitro CNS technologies. We provide an overview of some of the main recent developments (since 2015) in in vitro CNS models. In particular, we focus on engineered in vitro models based on cell culture systems combined with microfluidic platforms (e.g. 'organ-on-a-chip' systems). We delve into the fundamental principles underlying these systems and review several applications of these platforms for the study of the CNS in health and disease. Our discussion further addresses the challenges that hinder the implementation of advanced in vitro platforms in personalized medicine or in large-scale industrial settings, and outlines the existing differentiation protocols and industrial cell sources. We conclude by providing practical guidelines for laboratories that are considering adopting organ-on-a-chip technologies.

  • 37. Novak, R.
    et al.
    Ingram, M.
    Marquez, S.
    Das, D.
    Delahanty, A.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Maoz, B. M.
    Jeanty, S. S. F.
    Somayaji, M. R.
    Burt, M.
    Calamari, E.
    Chalkiadaki, A.
    Cho, A.
    Choe, Y.
    Chou, D. B.
    Cronce, M.
    Dauth, S.
    Divic, T.
    Fernandez-Alcon, J.
    Ferrante, T.
    Ferrier, J.
    FitzGerald, E. A.
    Fleming, R.
    Jalili-Firoozinezhad, S.
    Grevesse, T.
    Goss, J. A.
    Hamkins-Indik, T.
    Henry, O.
    Hinojosa, C.
    Huffstater, T.
    Jang, K. -J
    Kujala, V.
    Leng, L.
    Mannix, R.
    Milton, Y.
    Nawroth, J.
    Nestor, B. A.
    Ng, C. F.
    O’Connor, B.
    Park, T. -E
    Sanchez, H.
    Sliz, J.
    Sontheimer-Phelps, A.
    Swenor, B.
    Thompson, G. , I I
    Touloumes, G. J.
    Tranchemontagne, Z.
    Wen, N.
    Yadid, M.
    Bahinski, A.
    Hamilton, G. A.
    Levner, D.
    Levy, O.
    Przekwas, A.
    Prantil-Baun, R.
    Parker, K. K.
    Ingber, D. E.
    Robotic fluidic coupling and interrogation of multiple vascularized organ chips2020In: Nature Biomedical Engineering, E-ISSN 2157-846XArticle in journal (Refereed)
    Abstract [en]

    Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.

  • 38.
    Ouyang, Liangqi
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Buchmann, Sebastian
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Benselfelt, Tobias
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Musumeci, Chiara
    Laboratory of Organic Electronics, ITN, Linköping University, Campus Norrköping, SE 60221, Sweden.
    Wang, Zhen
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Khaliliazar, Shirin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Tian, Weiqian
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Li, Hailong
    Fysikum, Stockhohlm University, Roslagstullsbacken 21, Stockholm, Sweden.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hamedi, Mahiar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Rapid prototyping of heterostructured organic microelectronics using wax printing, filtration, and transfer2021In: Journal of Materials Chemistry C, ISSN 2050-7526, E-ISSN 2050-7534, Vol. 9, no 41, p. 14596-14605Article in journal (Refereed)
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  • 39.
    Park, Tae-Eun
    et al.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;UNIST, UNIST Gil 50, Ulsan 44919, South Korea..
    Mustafaoglu, Nur
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Harvard Univ, USA ;Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, Stockholm, Sweden..
    Hasselkus, Ryan
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Mannix, Robert
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA..
    FitzGerald, Edward A.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Prantil-Baun, Rachelle
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Watters, Alexander
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Henry, Olivier
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Benz, Maximilian
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    Sanchez, Henry
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
    McCrea, Heather J.
    Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Goumnerova, Liliana Christova
    Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Song, Hannah W.
    Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA..
    Palecek, Sean P.
    Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA..
    Shusta, Eric
    Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA..
    Ingber, Donald E.
    Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA..
    Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies2019In: Nature Communications, E-ISSN 2041-1723, Vol. 10, article id 2621Article in journal (Refereed)
    Abstract [en]

    The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.

  • 40.
    Pezeshkpour, Pegah
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Multidirectional Lithography of Cell-Laden Hydrogels2021In: 21st International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2021, Institute of Electrical and Electronics Engineers (IEEE) , 2021, p. 908-911Conference paper (Refereed)
    Abstract [en]

    Controlled microstructuring of cell culture environments is of interest in life science applications such as bioreactor optimization. Here we introduce multidirectional UV lithography of a photoresist consisting of the biocompatible hydrophilic hydrogel PEGDA preloaded with cells. By culturing the cells in sugar solution before adding them to the resist, we enabled refractive index matching between the gel and the cells, thus minimizing spurious light scattering during photostructuring. We created 3D-periodic porous scaffolds of interlocked micropillars of diameter 250 mu m and pitch 1 mm, where 1% w/w yeast cells were incorporated inside the solid pillar fraction with high cell viability.

  • 41. Rajewsky, N.
    et al.
    Almouzni, G.
    Gorski, S. A.
    Aerts, S.
    Amit, I.
    Bertero, M. G.
    Bock, C.
    Bredenoord, A. L.
    Cavalli, G.
    Chiocca, S.
    Clevers, H.
    De Strooper, B.
    Eggert, A.
    Ellenberg, J.
    Fernández, X. M.
    Figlerowicz, M.
    Gasser, S. M.
    Hubner, N.
    Kjems, J.
    Knoblich, J. A.
    Krabbe, G.
    Lichter, P.
    Linnarsson, S.
    Marine, J. -C
    Marioni, J.
    Marti-Renom, M. A.
    Netea, M. G.
    Nickel, D.
    Nollmann, M.
    Novak, H. R.
    Parkinson, H.
    Piccolo, S.
    Pinheiro, I.
    Pombo, A.
    Popp, C.
    Reik, W.
    Roman-Roman, S.
    Rosenstiel, P.
    Schultze, J. L.
    Stegle, O.
    Tanay, A.
    Testa, G.
    Thanos, D.
    Theis, F. J.
    Torres-Padilla, M. -E
    Valencia, A.
    Vallot, C.
    van Oudenaarden, A.
    Vidal, M.
    Voet, T.
    Alberi, L.
    Alexander, S.
    Alexandrov, T.
    Arenas, E.
    Bagni, C.
    Balderas, R.
    Bandelli, A.
    Becher, B.
    Becker, M.
    Beerenwinkel, N.
    Benkirame, M.
    Beyer, M.
    Bickmore, W.
    Biessen, E. E. A. L.
    Blomberg, N.
    Blumcke, I.
    Bodenmiller, B.
    Borroni, B.
    Boumpas, D. T.
    Bourgeron, T.
    Bowers, S.
    Braeken, D.
    Brooksbank, C.
    Brose, N.
    Bruining, H.
    Bury, J.
    Caporale, N.
    Cattoretti, G.
    Chabane, N.
    Chneiweiss, H.
    Cook, S. A.
    Curatolo, P.
    de Jonge, M. I.
    Deplancke, B.
    de Witte, P.
    Dimmeler, S.
    Draganski, B.
    Drews, A. -D
    Dumbrava, C.
    Engelhardt, S.
    Gasser, T.
    Giamarellos-Bourboulis, E. J.
    Graff, C.
    Grün, D.
    Gut, I.
    Hansson, O.
    Henshall, D. C.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Heutink, P.
    Heymans, S. R. B.
    Heyn, H.
    Huch, M.
    Huitinga, I.
    Jackowiak, P.
    Jongsma, K. R.
    Journot, L.
    Junker, J. P.
    Katz, S.
    Kehren, J.
    Kempa, S.
    Kirchhof, P.
    Klein, C.
    Koralewska, N.
    Korbel, J. O.
    Kühnemund, M.
    Lamond, A. I.
    Lauwers, E.
    Le Ber, I.
    Leinonen, V.
    Tobon, A. L.
    Lundberg, E.
    Lunkes, A.
    Maatz, H.
    Mann, M.
    Marelli, L.
    Matser, V.
    Matthews, P. M.
    Mechta-Grigoriou, F.
    Menon, R.
    Nielsen, A. F.
    Pagani, M.
    Pasterkamp, R. J.
    Pitkanen, A.
    Popescu, V.
    Pottier, C.
    Puisieux, A.
    Rademakers, R.
    Reiling, D.
    Reiner, O.
    Remondini, D.
    Ritchie, C.
    Rohrer, J. D.
    Saliba, A. -E
    Sanchez-Valle, R.
    Santosuosso, A.
    Sauter, A.
    Scheltema, R. A.
    Scheltens, P.
    Schiller, H. B.
    Schneider, A.
    Seibler, P.
    Sheehan-Rooney, K.
    Shields, D.
    Sleegers, K.
    Smit, G.
    Smith, K. G. C.
    Smolders, I.
    Synofzik, M.
    Tam, W. L.
    Teichmann, S.
    Thom, M.
    Turco, M. Y.
    van Beusekom, H. M. M.
    Vandenberghe, R.
    den Hoecke, S. V.
    Van de Poel, I.
    der Ven, A.
    van der Zee, J.
    van Lunzen, J.
    van Minnebruggen, G.
    Van Paesschen, W.
    van Swieten, J.
    van Vught, R.
    Verhage, M.
    Verstreken, P.
    Villa, C. E.
    Vogel, J.
    von Kalle, C.
    Walter, J.
    Weckhuysen, S.
    Weichert, W.
    Wood, L.
    Ziegler, A. -G
    Zipp, F.
    Community, LifeTime
    LifeTime and improving European healthcare through cell-based interceptive medicine2020In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 587, no 7834, p. 377-386Article in journal (Refereed)
    Abstract [en]

    LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

  • 42.
    Reyes, Darwin R.
    et al.
    National Institute of Standards and Technology (NIST) Gaithersburg MD USA.
    Esch, Mandy B.
    National Institute of Standards and Technology (NIST) Gaithersburg MD USA.
    Ewart, Lorna
    Emulate, Inc., Boston Massachusetts USA.
    Nasiri, Rohollah
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Sung, Kyung
    Food and Drug Administration (FDA) Silver Spring Maryland USA.
    Piergiovanni, Monica
    European Commission, Joint Research Centre (JRC), Ispra Italy.
    Lucchesi, Carolina
    BioneXus Foundation, ATCC, Manassas VA USA.
    Shoemaker, James T.
    Lena Biosciences, Inc., Atlanta Georgia USA.
    Vukasinovic, Jelena
    Lena Biosciences, Inc., Atlanta Georgia USA.
    Nakae, Hiroki
    JMAC Japan bio Measurement & Analysis Consortium Tokyo Japan.
    Hickman, James
    Hesperos, Inc., Orlando Florida USA.
    Pant, Kapil
    SynVivo, Inc., Huntsville Alabama USA.
    Taylor, Anne
    Xona Microfluidics, Inc., Research Triangle Park, North Carolina USA.
    Heinz, Niki
    Altis Biosystems, Inc., Durham North Carolina USA.
    Ashammakhi, Nureddin
    Institute for Quantitative Health Science and Engineering, Department of Biomedical Engineering, College of Engineering, and College of Human Medicine, Michigan State University, East Lansing MI USA.
    From animal testing to in vitro systems: advancing standardization in microphysiological systems2024In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 24, no 5, p. 1076-1087Article, review/survey (Refereed)
    Abstract [en]

    Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment, and in vitro pre-clinical evaluation. This has resulted in the development of microfluidic-based cultures that may better represent organs and organ systems in vivo than conventional monolayer cell cultures. Although there is considerable interest from industry and regulatory bodies in this technology, several challenges need to be addressed for it to reach its full potential. Among those is a lack of guidelines and standards. Therefore, a multidisciplinary team of stakeholders was formed, with members from the US Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST), European Union, academia, and industry, to provide a framework for future development of guidelines/standards governing engineering concepts of organ-on-a-chip models. The result of this work is presented here for interested parties, stakeholders, and other standards development organizations (SDOs) to foster further discussion and enhance the impact and benefits of these efforts.

  • 43.
    Roberto de Barros, Natan
    et al.
    Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90064, USA.
    Nasiri, Rohollah
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Khademhosseini, Ali
    Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90064, USA.
    et al.,
    Engineered organoids for biomedical applications2023In: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 203, article id 115142Article, review/survey (Refereed)
    Abstract [en]

    As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.

  • 44.
    Tujula, I.
    et al.
    Tampere Univ, Fac Med & Hlth Technol, Neuroimmunol Res Grp, Tampere, Finland..
    Hyvarinen, T.
    Tampere Univ, Fac Med & Hlth Technol, Neuroimmunol Res Grp, Tampere, Finland..
    Lotila, J.
    Tampere Univ, Fac Med & Hlth Technol, Neuroimmunol Res Grp, Tampere, Finland..
    Jantti, H.
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Neuroinflammat Res Grp, Fac Hlth Sci, Kuopio, Finland..
    Ohtonen, S.
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Neuroinflammat Res Grp, Fac Hlth Sci, Kuopio, Finland..
    Sukki, L.
    Tampere Univ, Fac Med & Hlth Technol, Micro & Nanosyst Res Grp, Tampere, Finland..
    Tornberg, K.
    Tampere Univ, Fac Med & Hlth Technol, Micro & Nanosyst Res Grp, Tampere, Finland..
    Voulgaris, Dimitrios
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. Karolinska Inst, AIMES Ctr Adv Integrated Med & Engn Sci, Solna, Sweden.;Karolinska Inst, Dept Neurosci, Solna, Sweden..
    Rogal, Julia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, AIMES Ctr Adv Integrated Med & Engn Sci, Solna, Sweden.;Karolinska Inst, Dept Neurosci, Solna, Sweden..
    Malm, T.
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Neuroinflammat Res Grp, Fac Hlth Sci, Kuopio, Finland..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. ;Karolinska Inst, , AIMES Ctr Adv Integrated Med & Engn Sci, Solna, Sweden.;Karolinska Inst, Dept Neurosci, Solna, Sweden..
    Kallio, P.
    Tampere Univ, Fac Med & Hlth Technol, Micro & Nanosyst Res Grp, Tampere, Finland..
    Narkilahti, S.
    Tampere Univ, Fac Med & Hlth Technol, NeuroGrp, Tampere, Finland..
    Hagman, S.
    Tampere Univ, Fac Med & Hlth Technol, Neuroimmunol Res Grp, Tampere, Finland..
    Human iPSC glial co-culture chip model for studying neuroinflammation in vitro2023In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 71, p. E964-E964Article in journal (Other academic)
  • 45.
    Voulgaris, Dimitrios
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Jain, Saumey
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Hesen, Rick
    Moslem, Mohsen
    Falk, Anna
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    On-chip neural induction boosts neural stem cell commitment and stabilization: toward a pipeline for iPSC-based therapiesManuscript (preprint) (Other academic)
  • 46.
    Voulgaris, Dimitrios
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nikolakopoulou, Polyxeni
    KTH.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Generation of Human iPSC-Derived Astrocytes with a mature star-shaped phenotype for CNS modeling2022In: Stem Cell Reviews and Reports, ISSN 2629-3269Article in journal (Refereed)
    Abstract [en]

    The generation of astrocytes from human induced pluripotent stem cells has been hampered by either prolonged diferentiation—spanning over two months—or by shorter protocols that generate immature astrocytes, devoid of salient matureastrocytic traits pivotal for central nervous system (CNS) modeling. We directed stable hiPSC-derived neuroepithelial stemcells to human iPSC-derived Astrocytes (hiAstrocytes) with a high percentage of star-shaped cells by orchestrating anastrocytic-tuned culturing environment in 28 days. We employed RT-qPCR and ICC to validate the astrocytic commitmentof the neuroepithelial stem cells. To evaluate the infammatory phenotype, we challenged the hiAstrocytes with the proinfammatory cytokine IL-1β (interleukin 1 beta) and quantitatively assessed the secretion profle of astrocyte-associatedcytokines and the expression of intercellular adhesion molecule 1 (ICAM-1). Finally, we quantitatively assessed the capacityof hiAstrocytes to synthesize and export the antioxidant glutathione. In under 28 days, the generated cells express canonicaland mature astrocytic markers, denoted by the expression of GFAP, AQP4 and ALDH1L1. In addition, the notion of a maturephenotype is reinforced by the expression of both astrocytic glutamate transporters EAAT1 and EAAT2. Thus, hiAstrocyteshave a mature phenotype that encompasses traits critical in CNS modeling, including glutathione synthesis and secretion,upregulation of ICAM-1 and a cytokine secretion profle on a par with human fetal astrocytes. This protocol generates amultifaceted astrocytic model suitable for in vitro CNS disease modeling and personalized medicine.

    Download full text (pdf)
    fulltext
  • 47.
    Voulgaris, Dimitrios
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Rogal, Julia
    Nikolakopoulou, Polyxeni
    Saei Dibavar, Amirata
    Gaetani, Massimiliano
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Proteomic profiling reveals that human iPSC-derived astrocytes resemble their primary counterpartManuscript (preprint) (Other academic)
  • 48. Wang, Y.
    et al.
    Zeglio, Erica
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Wang, L.
    Cong, S.
    Zhu, G.
    Liao, H.
    Duan, J.
    Zhou, Y.
    Li, Z.
    Mawad, D.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Center for Integrated Medical and Engineering Sciences, Department of Neuroscience, Karolinska Institute, Stockholm, 17177 Sweden.
    Yue, W.
    McCulloch, I.
    Green Synthesis of Lactone-Based Conjugated Polymers for n-Type Organic Electrochemical Transistors2022In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 32, no 16, article id 2111439Article in journal (Refereed)
    Abstract [en]

    As new and better materials are implemented for organic electrochemical transistors (OECTs), it becomes increasingly important to adopt more economic and environmentally friendly synthesis pathways with respect to conventional transition-metal-catalyzed polymerizations. Herein, a series of novel n-type donor–acceptor-conjugated polymers based on glycolated lactone and bis-isatin units are reported. All the polymers are synthesized via green and metal-free aldol polymerization. The strong electron-deficient lactone-building blocks provide low-lying lowest unoccupied molecular orbital (LUMO) and the rigid backbone needed for efficient electron mobility up to 0.07 cm2 V−1 s−1. Instead, polar atoms in the backbone and ethylene glycol side chains contribute to the ionic conductivity. The resulting OECTs exhibit a normalized maximum transconductance gm,norm of 0.8 S cm−1 and a μC* of 6.7 F cm−1 V−1 s−1. Data on the microstructure show that such device performance originates from a unique porous morphology together with a highly disordered amorphous microstructure, leading to efficient ion-to-electron coupling. Overall, the design strategy provides an inexpensive and metal-free polymerization route for high-performing n-type OECTs. 

  • 49.
    Wang, Yazhou
    et al.
    Sun Yat Sen Univ, Key Lab Polymer Composite & Funct Mat, Minist Educ, Sch Mat Sci & Engn, Guangzhou 510275, Guangdong, Peoples R China..
    Zeglio, Erica
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. UNSW, Sch Mat Sci & Engn, Sydney, NSW 2052, Australia ; UNSW, Ctr Adv Macromol Design, Sydney, NSW 2052, Australia.
    Liao, Hailiang
    Sun Yat Sen Univ, Key Lab Polymer Composite & Funct Mat, Minist Educ, Sch Mat Sci & Engn, Guangzhou 510275, Guangdong, Peoples R China..
    Xu, Jinqiu
    Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China..
    Liu, Feng
    Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China..
    Li, Zhengke
    Sun Yat Sen Univ, Key Lab Polymer Composite & Funct Mat, Minist Educ, Sch Mat Sci & Engn, Guangzhou 510275, Guangdong, Peoples R China..
    Maria, Iuliana Petruta
    Imperial Coll London, Dept Chem, London SW7 2AZ, England.;Imperial Coll London, Ctr Plast Elect, London SW7 2AZ, England..
    Mawad, Damia
    UNSW, Sch Mat Sci & Engn, Sydney, NSW 2052, Australia.;UNSW, Ctr Adv Macromol Design, Sydney, NSW 2052, Australia..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    McCulloch, Iain
    Imperial Coll London, Dept Chem, London SW7 2AZ, England.;Imperial Coll London, Ctr Plast Elect, London SW7 2AZ, England.;KAUST, SPERC, Thuwal 239556900, Saudi Arabia..
    Yue, Wan
    Sun Yat Sen Univ, Key Lab Polymer Composite & Funct Mat, Minist Educ, Sch Mat Sci & Engn, Guangzhou 510275, Guangdong, Peoples R China..
    Hybrid Alkyl-Ethylene Glycol Side Chains Enhance Substrate Adhesion and Operational Stability in Accumulation Mode Organic Electrochemical Transistors2019In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 31, no 23, p. 9797-9806Article in journal (Refereed)
    Abstract [en]

    Donor-acceptor copolymers featuring electron-deficient isoindigo units and electron-rich 3,4-ethyl-E enedioxy (EDOT) groups are presented as new materials for accumulation mode organic electrochemical transistors (OECTs). Grafting hybrid alkyl-ethylene glycol side chains on the isoindigo units of the copolymer leads to OECTs with outstanding substrate adhesion and operational stability in contact with an aqueous electrolyte, as demonstrated by their preserved performance after extensive ultrasonication (1.5 h) or after continuous on-off switching for over 6 h. Hybrid side chains outperform copolymers with alkyl only or ethylene glycol only side chains, which retain only 27% and 10% of the on currents after 40 min of on-off switching, respectively, under the same biasing conditions. These devices are promising candidates for in vitro and in vivo bioelectronics, applications where stability as well as robust adhesion of the conjugated polymer to the substrate are essential.

  • 50.
    Wang, Yazhou
    et al.
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Zhu, Genming
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Zeglio, Erica
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden.
    Castillo, Tania Cecilia Hidalgo
    Biological and Environmental Science and Engineering (BESE) Organic Bioelectronics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
    Haseena, Sheik
    Department of Chemistry, SRM University AP, Amaravati 522240, India.
    Ravva, Mahesh Kumar
    Department of Chemistry, SRM University AP, Amaravati 522240, India.
    Cong, Shengyu
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Chen, Junxin
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Lan, Liuyuan
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Li, Zhengke
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
    Herland, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden.
    Mcculloch, Iain
    Department of Chemistry Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K..
    Inal, Sahika
    Biological and Environmental Science and Engineering (BESE) Organic Bioelectronics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
    Yue, Wan
    Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China; Department of Chemistry Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K..
    n-Type Organic Electrochemical Transistors with High Transconductance and Stability2023In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 35, no 2, p. 405-415Article in journal (Refereed)
    Abstract [en]

    An n-type conjugated polymer based on diazaisoindigo (AIID) and fluorinated thiophene units is introduced. Combining the strong electron-accepting properties of AIID with backbone fluorination produced gAIID-2FT, leading to organic electrochemical transistors (OECTs) with normalized values of 4.09 F cm-1 V-1 s-1 and a normalized transconductance (gm,norm) of 0.94 S cm-1. The resulting OECTs exhibit exceptional operational stability and long shelf-life in ambient conditions, preserving 100% of the original maximum drain current after over 3 h of continuous operation and 28 days of storage in the air. Our work highlights the advantages of integrating strong electron acceptors with donor fluorination to boost the performance and stability of n-type OECTs.

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