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  • 1.
    Abramson, Alex
    et al.
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Caffarel-Salvador, Ester
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Khang, Minsoo
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Dellal, David
    MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Silverstein, David
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Gao, Yuan
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Frederiksen, Morten Revsgaard
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Vegge, Andreas
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Hubalek, Frantisek
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Water, Jorrit J.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Friderichsen, Anders V.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Fels, Johannes
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Kirk, Rikke Kaae
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Cleveland, Cody
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Collins, Joy
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Tamang, Siddartha
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Hayward, Alison
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, Cambridge, MA 02139 USA..
    Landh, Tomas
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Buckley, Stephen T.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Rahbek, Ulrik
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Langer, Robert
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Media Lab, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA..
    An ingestible self-orienting system for oral delivery of macromolecules2019In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 363, no 6427, p. 611-+Article in journal (Refereed)
    Abstract [en]

    Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

  • 2.
    Abramson, Alex
    et al.
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Caffarel-Salvador, Ester
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Soares, Vance
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Minahan, Daniel
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tian, Ryan Yu
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Lu, Xiaoya
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Dellal, David
    MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Gao, Yuan
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Kim, Soyoung
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Wainer, Jacob
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Collins, Joy
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tamang, Siddartha
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Hayward, Alison
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, Cambridge, MA 02139 USA..
    Yoshitake, Tadayuki
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Lee, Hsiang-Chieh
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Fujimoto, James
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Fels, Johannes
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Frederiksen, Morten Revsgaard
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Rahbek, Ulrik
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems. MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Langer, Robert
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;MIT, Media Lab, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA..
    A luminal unfolding microneedle injector for oral delivery of macromolecules2019In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 10, p. 1512-+Article in journal (Refereed)
    Abstract [en]

    Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes(1,2), yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications(3-5). Compared with subcutaneously administered drugs, oral formulations create less patient discomfort(4), show greater chemical stability at high temperatures(6), and do not generate biohazardous needle waste(7). An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract(8). We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake > 10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.

  • 3.
    Gatty, Hithesh K.
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    A Miniaturized Amperometric Hydrogen Sulfide Sensor Applicable for Bad Breath Monitoring2018In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, Vol. 9, no 12, article id 612Article in journal (Refereed)
    Abstract [en]

    Bad breath or halitosis affects a majority of the population from time to time, causing personal discomfort and social embarrassment. Here, we report on a miniaturized, microelectromechanical systems (MEMS)-based, amperometric hydrogen sulfide (H2S) sensor that potentially allows bad breath quantification through a small handheld device. The sensor is designed to detect H2S gas in the order of parts-per-billion (ppb) and has a measured sensitivity of 0.65 nA/ppb with a response time of 21 s. The sensor was found to be selective to NO and NH3 gases, which are normally present in the oral breath of adults. The ppb-level detection capability of the integrated sensor, combined with its relatively fast response and high sensitivity to H2S, makes the sensor potentially applicable for oral breath monitoring.

  • 4.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Lenk, Gabriel
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Hansson, Jonas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Beck, Olof
    Karolinska Inst, Dept Lab Med, S-14186 Stockholm, Sweden..
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    High-Yield Passive Plasma Filtration from Human Finger Prick Blood2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 22, p. 13393-13399Article in journal (Refereed)
    Abstract [en]

    Whole-blood microsampling provides many benefits such as remote, patient-centric, and minimally invasive sampling. However, blood plasma, and not whole blood, is the prevailing matrix in clinical laboratory investigations. The challenge with plasma microsampling is to extract plasma volumes large enough to reliably detect low-concentration analytes from a small finger prick sample. Here we introduce a passive plasma filtration device that provides a high extraction yield of 65%, filtering 18 mu L of plasma from 50 mu L of undiluted human whole blood (hematocrit 45%) within less than 10 min. The enabling design element is a wedge-shaped connection between the blood filter and the hydrophilic bottom surface of a capillary channel. Using finger prick and venous blood samples from more than 10 healthy volunteers, we examined the filtration kinetics of the device over a hematocrit range of 35-55% and showed that 73 +/- 8% of the total protein content was successfully recovered after filtration. The presented plasma filtration device tackles a major challenge toward patient-centric blood microsampling by providing high-yield plasma filtration, potentially allowing reliable detection of low-concentration analytes from a blood microsample.

  • 5.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Lenk, Gabriel
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Ullah, Shahid
    Karolinska Univ Hosp, Clin Pharmacol, S-11486 Stockholm, Sweden..
    Beck, Olof
    Karolinska Univ Hosp, Clin Pharmacol, S-11486 Stockholm, Sweden..
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots2019In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 11, p. 7125-7130Article in journal (Refereed)
    Abstract [en]

    Obtaining plasma from a blood sample and preparing it for subsequent analysis is currently a laborious process involving experienced health-care professionals and centrifugation. We circumvent this by utilizing capillary forces and microfluidic engineering to develop an autonomous plasma sampling device that filters and stores an exact amount of plasma as a dried plasma spot (DPS) from a whole blood sample in less than 6 min. We tested 24 prototype devices with whole blood from 10 volunteers, various input volumes (40-80 mu L), and different hematocrit levels (39-45%). The resulting mean plasma volume, assessed gravimetrically, was 11.6 mu L with a relative standard deviation similar to manual pipetting (3.0% vs 1.4%). LC-MS/MS analysis of caffeine concentrations in the generated DPS (12 duplicates) showed a strong correlation (R-2 = 0.99) to, but no equivalence with, concentrations prepared from corresponding plasma obtained by centrifugation. The presented autonomous DPS device may enable patient-centric plasma sampling through minimally invasive finger-pricking and allow generatation of volume-defined DPS for quantitative blood analysis.

  • 6.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    A BLOOD HEMATOCRIT TEST STRIP2019Conference paper (Other academic)
    Abstract [en]

    This paper reports a self-propelled microfluidichematocrit (HCT) test that uses the correlation betweenblood hematocrit and wicking distance of blood in a specialpaper matrix. The enabling feature is a novel blood volumemetering method that allows sampling from the fingertipand reliably generates a highly precise blood volume of47.7 ± 1.9 μl (CV 4%) that is transferred into a porouspaper matrix. A dissolvable valve ensures a relaxed timewindow for blood sampling, making it highly user-friendlyand resilient to overfilling. The presented hematocrit teststrip poses a simple, cheap, equipment-free solution forpatient-centric hematocrit measurements.

  • 7.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    AN AUTONOMOUS BLOOD MICROSAMPLING DEVICE ENABLING METERED LARGE-VOLUME DRIED PLASMA SPOTS (DPS)2018Conference paper (Other academic)
    Abstract [en]

    This work introduces a novel principle for volume metering of passively separated blood plasma, empowered by an air pinch-off structure and the high capillary force of a paper matrix. The presented microfluidic device enables the autonomous generation of large-volume dried plasma spots (DPS) with 16 μl of plasma from 50-100 μl of human whole blood within less than 10 minutes. Providing large-volume DPS increases the confidence level of detecting low concentration analytes and constitutes a step towards using blood microsampling in the everyday blood analysis routine.

  • 8.
    Last, Torben Sebastian
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Demonstration of the first self-sealing aerosol spray nozzle for medical drug delivery2019In: Demonstration of first self-sealing aerosol spray nozzle for medical drug delivery, 2019, Vol. 32, p. 1-4Conference paper (Refereed)
    Abstract [en]

    Portable medical inhaler systems are prone to bacterial contamination and ingrowth. Here we demonstrate thefirst valved aerosol spray chip, a system that sprays a microjet when actuated and seals against bacterial ingrowth into the spray nozzle in the closed state by a sufficiently small gap. The sealing mechanism is realized by placing a valve seat directly underneath the spray orifices. We fabricated and characterized spray chips with and without valve mechanism and show that they haveindistinguishable spray performance. Our system aims to enable the safe reuse of spray chips for multiple spray operations over an extended period, lowering the cost of treatment while increasing patient compliance.

  • 9.
    Lenk, Gabriel
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Ullah, S.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Beck, O.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Evaluation of a Volumetric Dried Blood Spot Card Using a Gravimetric Method and a Bioanalytical Method with Capillary Blood from 44 Volunteers2019In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 9, p. 5558-5565Article in journal (Refereed)
    Abstract [en]

    Dried blood spot (DBS) sampling is a promising method for collection of microliter blood samples. However, hematocrit-related bias in combination with subpunch analysis can result in inaccurate quantification of analytes in DBS samples. In this study we use a microfluidic DBS card, designed to automatically collect fixed volume DBS samples irrespective of the blood hematocrit, to measure caffeine concentration in normal finger prick samples obtained from 44 human individuals. Caffeine levels originating from blood drops of unknown volume collected on the volumetric microfluidic DBS card were compared to volume-controlled pipetted DBS samples from the same finger prick. Hematocrit independence and volumetric sampling performances were also verified on caffeine-spiked blood samples in vitro, using both LC-MS/MS and gravimetric methods, on hematocrits from 26 to 62%. The gravimetric measurements show an excellent metering performance of the microfluidic DBS card, with a mean blood sample volume of 14.25 μL ± 3.0% (n = 51). A measured mean bias below 2.9% compared to normal hematocrit (47%) demonstrates that there is no significant hematocrit-induced bias. LC-MS/MS measurements confirm low CV and hematocrit independence of the sampling system and exhibit no substantial mean bias compared to pipetted DBS. Tests with 44 individuals demonstrated applicability of the microfluidic DBS card for direct finger prick blood sampling, and measured caffeine concentrations show a good agreement with measurements of pipetted DBS. The presented concept demonstrates a good volumetric performance which can help to improve the accuracy of DBS analysis by analyzing a whole spot, equivalent to a defined volume of liquid blood.

  • 10. Nadeau, P.
    et al.
    El-Damak, D.
    Glettig, D.
    Kong, Y. L.
    Mo, S.
    Cleveland, C.
    Booth, L.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems. Massachusetts Institute of Technology, United States.
    Langer, R.
    Chandrakasan, A. P.
    Traverso, G.
    Prolonged energy harvesting for ingestible devices2017In: Nature Biomedical Engineering, ISSN 2157-846X, Vol. 1, no 3, article id 0022Article in journal (Refereed)
    Abstract [en]

    Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged-monitoring systems for patients. Although previous biocompatible power-harvesting systems for in vivo use have demonstrated short (minute-long) bursts of power from the stomach, little is known about the potential for powering electronics in the longer term and throughout the gastrointestinal tract. Here, we report the design and operation of an energy-harvesting galvanic cell for continuous in vivo temperature sensing and wireless communication. The device delivered an average power of 0.23 μW mm -2 of electrode area for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs. This power-harvesting cell could provide power to the next generation of ingestible electronic devices for prolonged periods of time inside the gastrointestinal tract.

  • 11.
    Parrilla, Marc
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Cuartero, Maria
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Sanchez, Sara Padrell
    Karolinska Inst, Dept Clin Sci Intervent & Technol, K 57, SE-14186 Stockholm, Sweden.;Karolinska Univ Sjukhuset, Div Obstet & Gynecol, S-14186 Stockholm, Sweden..
    Rajabi, Mina
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Crespo, Gaston A.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection2019In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 2, p. 1578-1586Article in journal (Refereed)
    Abstract [en]

    A new analytical all-solid-state platform for intradermal potentiometric detection of potassium in interstitial fluid is presented here. Solid microneedles are modified with different coatings and polymeric membranes to prepare both the potassium-selective electrode and reference electrode needed for the potentiometric readout. These microneedle-based electrodes are fixed in an epidermal patch suitable for insertion into the skin. The analytical performances observed for the potentiometric cell (Nernstian slope, limit of detection of 10(-4.9) potassium activity, linear range of 10(-4.2) to 10(-1.1), drift of 0.35 +/- 0.28 mV h(-1)), together with a fast response time, adequate selectivity, and excellent reproducibility and repeatability, are appropriate for potassium analysis in interstitial fluid within both clinical and harmful levels. The potentiometric response is maintained after several insertions into animal skin, confirming the resiliency of the microneedle-based sensor. Ex vivo tests based on the intradermal detection of potassium in chicken and porcine skin demonstrate that the microneedle patch is suitable for monitoring potassium changes inside the skin. In addition, the dimensions of the microneedles modified with the corresponding layers necessary to enhance robustness and provide sensing capabilities (1000 mu m length, 45 degrees tip angle, 15 mu m thickness in the tip, and 435 mu m in the base) agree with the required ranges for a painless insertion into the skin. In vitro cytotoxicity experiments showed that the patch can be used for at least 24 h without any side effect for the skin cells. Overall, the developed concept constitutes important progress in the intradermal analysis of ions related to an electrolyte imbalance in humans, which is relevant for the control of certain types of diseases.

  • 12.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    De Luca, Eleonora
    KTH, School of Engineering Sciences (SCI), Applied Physics, Quantum and Biophotonics.
    Ottonello Briano, Floria
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Swillo, Marcin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Quantum and Biophotonics.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Zero-insertion-loss optical shutter based on electrowetting-on-dielectric actuation of opaque ionic liquid microdroplets2019In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 115, no 7, article id 073502Article in journal (Refereed)
    Abstract [en]

    This article reports a broad-band optical shutter based on microdroplet actuation with zero optical insertion loss in the open state. These features are achieved by electrowetting-on-dielectric (EWOD) actuation of opaque ionic liquid microdroplets. The negligible vapor pressure of ionic liquids allows the device to robustly operate in open air, unlike previously proposed EWOD-based systems in which the light crosses several attenuating and reflective layers, preventing broad-band operation and creating insertion losses > 14%. The presented device provides an attenuation of 78dB in the closed state and a transmission of >99.99999% in the open state and can operate in the visible and mid-infrared wavelength range. Moreover, the switch can sustain larger incoming laser powers (5 mW continuous exposure or up to 3h of continuous exposure at similar to 100mW) compared to the values reported for other state-of-the-art EWOD-based shutters. Additionally, the proposed device is compact, operates with low voltage (<25V peak voltage), and features zero static power consumption.

  • 13.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    De Luca, Eleonora
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ottonello Briano, Floria
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Swillo, Marcin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Zero-Loss Optical Switch Based on Ionic Liquid Microdroplet Ewod Actuatio2019In: 2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems and Eurosensors XXXIII, TRANSDUCERS 2019 and EUROSENSORS XXXIII, Institute of Electrical and Electronics Engineers (IEEE), 2019, p. 2290-2293, article id 8808243Conference paper (Refereed)
    Abstract [en]

    This paper reports the first optical shutter based on electrical actuation of microdroplets featuring zero insertion loss in the open state and broad-band operation. These features are achieved by electrowetting-on-dielectric (EWOD) actuation of ionic liquid microdroplets. Due to their negligible vapor pressure, ionic liquids allow the switch to robustly operate in air, unlike previously proposed systems in which the light had to cross several attenuating and refractive layers. Moreover, this solution enables operation in a much wider wavelength range, e.g. in the infrared spectrum where glass has strong absorption. Additionally, the proposed device requires lower voltage to operate (25 V) and features zero static power consumption.

  • 14.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    De Pietro, Luca
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Gas diffusion and evaporation control using EWOD actuation of ionic liquid microdroplets for gas sensing applications2018In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 267, p. 647-654Article in journal (Refereed)
    Abstract [en]

    The lifetime of electrochemical gas sensors suffers from electrolyte evaporation and from the impracticality to perform recalibration. To tackle these issues, a prototype of a microfabricated gas diffusion controlling system, based on coplanar electrowetting-on-dielectric (EWOD) actuation of ionic liquid microdroplets, is presented. The system is designed to be integrated with electrochemical gas sensors to allow on-demand sealing of the sensing chamber from the environment. The MEMS device can be electrically toggled between an open and a closed state, in which the microdroplets are used to cover or uncover the openings of a perforated membrane connecting to the sensing compartment, respectively. This ON/OFF diffusion-blocking valve mechanism potentially allows for recalibration and for liquid electrolyte evaporation reduction when the sensor is not in use, thus extending the gas sensor lifetime. A one order of magnitude reduction of evaporation rate and a more than three orders of magnitude reduction of gas diffusion time were experimentally demonstrated. Ionic liquid movement can be performed with an applied AC voltage as low as 18 V, using super-hydrophobic cover plates to facilitate droplet motion. Furthermore, the shown ionic liquid micro-droplet manipulation provides a robust and low voltage platform for digital microfluidics, readily adaptable to serve different applications.

  • 15.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    De Pietro, Luca
    KTH.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Ionic liquid microdroplet manipulation by electrowetting-on-dielectric for on/off diffusion control2018In: 2018 IEEE Micro Electro Mechanical Systems (MEMS), Institute of Electrical and Electronics Engineers (IEEE), 2018, p. 1181-1184Conference paper (Refereed)
    Abstract [en]

    This article presents a proof-of-concept of a device able to control (ON/OFF) gas diffusion through a perforated membrane. The microfabricated system is based on electrowetting-on-dielectric (EWOD) actuation of ionic liquid (IL) microdroplets and can be electrically toggled from an open to a closed state, in which microdroplets cover or uncover the membrane openings, respectively. The system is designed to be integrated with liquid-electrolyte-based electrochemical gas sensors, to extend their lifetime by reducing electrolyte evaporation and allowing recalibration. The realized device was proven to limit gas diffusion and water evaporation through perforated portions of thin membranes on command.

  • 16.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    Microneedle-based system for minimally invasive continuous monitoring of glucose in the dermal interstitial fluid2018In: 2018 IEEE Micro Electro Mechanical Systems (MEMS), Institute of Electrical and Electronics Engineers (IEEE), 2018, Vol. 2018, p. 408-411Conference paper (Refereed)
    Abstract [en]

    We present a minimally invasive continuous glucose monitoring (CGM) device. The system consists in an ultra-miniaturized electrochemical sensor probe (70 × 700 × 50 μm3) inserted into the lumen of a hollow silicon microneedle. The implantable portion of the system is 50-fold smaller than state-of-the-art commercial products, thus enabling glucose monitoring in the dermis and a less invasive insertion procedure. Passive interstitial fluid extraction is achieved, making the daily use of this system practically viable. Moreover, the sensor positioning provides minimal delay in tracking glycaemia (5-10 minutes lag), due to the minimal distance between sensing electrodes and microneedle opening. The demonstrated system has therefore the potential to enable minimally invasive, fast and reliable CGM in patients affected by diabetes.

  • 17.
    Ribet, Federico
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system2018In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 20, no 4, article id 101Article in journal (Refereed)
    Abstract [en]

    Continuous glucose monitoring (CGM) has the potential to greatly improve diabetes management. The aim of this work is to show a proof-of-concept CGM device which performs minimally invasive and minimally delayed in-situ glucose sensing in the dermal interstitial fluid, combining the advantages of microneedle-based and commercially available CGM systems. The device is based on the integration of an ultra-miniaturized electrochemical sensing probe in the lumen of a single hollow microneedle, separately realized using standard silicon microfabrication methods. By placing the sensing electrodes inside the lumen facing an opening towards the dermal space, real-time measurement purely can be performed relying on molecular diffusion over a short distance. Furthermore, the device relies only on passive capillary lumen filling without the need for complex fluid extraction mechanisms. Importantly, the transdermal portion of the device is 50 times smaller than that of commercial products. This allows access to the dermis and simultaneously reduces tissue trauma, along with being virtually painless during insertion. The three-electrode enzymatic sensor alone was previously proven to have satisfactory sensitivity (1.5 nA/mM), linearity (up to 14 mM), selectivity, and long-term stability (up to 4 days) in-vitro. In this work we combine this sensor technology with microneedles for reliable insertion in forearm skin. In-vivo human tests showed the possibility to correctly and dynamically track glycaemia over time, with approximately 10 min delay with respect to capillary blood control values, in line with the expected physiological lag time. The proposed device can thus reduce discomfort and potentially enable less invasive real-time CGM in diabetic patients.

  • 18.
    Schröder, Stephan
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Gatty, Hithesh Kumar
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    A low-cost nitric oxide gas sensor based on bonded gold wires2017In: TRANSDUCERS 2017 - 19th International Conference on Solid-State Sensors, Actuators and Microsystems, Institute of Electrical and Electronics Engineers (IEEE), 2017, p. 1457-1460, article id 7994334Conference paper (Refereed)
    Abstract [en]

    In this paper we report of a novel and very simple fabrication method for realizing amperometric gas sensors using conventional wire bonding technology. Working and counter electrodes are made of 360 vertically standing bond wires, entirely manufactured by a fully automated, standard wire bonding tool. Our process enables standing bond wires with a length of 1.24 mm, resulting in an extremely high aspect-ratio of 50, thus effectively increasing the surface area of the working electrode. All gas sensor electrodes are embedded in a polymer-based, solid electrolyte. Therefore, laborious handling of liquid electrolytes can be avoided. Here, we report of a nitric oxide (NO) gas sensor that is capable of detecting NO gas concentrations down to the single-digit ppm range. The proposed approach demonstrates the feasibility towards a scalable and entire back-end fabrication concept for low-cost NO gas sensors.

  • 19.
    Verma, Malvika
    et al.
    MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Vishwanath, Karan
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Eweje, Feyisope
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Med Sch, Div Gastroenterol Hepatol & Endoscopy, Brigham & Womens Hosp, Boston, MA 02115 USA..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Grant, Tyler
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Castaneda, Macy
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Steiger, Christoph
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Med Sch, Div Gastroenterol Hepatol & Endoscopy, Brigham & Womens Hosp, Boston, MA 02115 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Mazdiyasni, Hormoz
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Bensel, Taylor
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Minahan, Daniel
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Soares, Vance
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Salama, John A. F.
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Lopes, Aaron
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Hess, Kaitlyn
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Cleveland, Cody
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Fulop, Daniel J.
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Univ Delaware, Biomed Engn Dept, 161 Colburn Lab, Newark, DE 19716 USA..
    Hayward, Alison
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Collins, Joy
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tamang, Siddartha M.
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Hua, Tiffany
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Ikeanyi, Chinonyelum
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Zeidman, Gal
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Mule, Elizabeth
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Boominathan, Sooraj
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Popova, Ellena
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Miller, Jonathan B.
    MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Sloan Sch Management, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Bellinger, Andrew M.
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Med Sch, Dept Med, Cardiovasc Div, Boston, MA 02115 USA.;Lyndra Therapeut Inc, Watertown, MA 02472 USA..
    Collins, David
    Management Sci Hlth, Medford, MA 02155 USA.;Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA..
    Leibowitz, Dalia
    MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Batra, Shelly
    Operat ASHA, New Delhi 110076, India..
    Ahuja, Sandeep
    Operat ASHA, New Delhi 110076, India..
    Bajiya, Manju
    Operat ASHA, New Delhi 110076, India..
    Batra, Sonali
    Operat ASHA, New Delhi 110076, India..
    Sarin, Rohit
    Natl Inst TB & Resp Dis, New Delhi 110030, India..
    Agarwal, Upasna
    Natl Inst TB & Resp Dis, New Delhi 110030, India..
    Khaparde, Sunil D.
    Former Deputy Director Gen & Head Cent TB Div, New Delhi 110011, India..
    Gupta, Neeraj K.
    Safdarjang Hosp, Dept Resp Med, New Delhi 110029, India..
    Gupta, Deepak
    All India Inst Med Sci, Div Pulm & Crit Care Med, New Delhi 110029, India..
    Bhatnagar, Anuj K.
    Rajan Babu Inst Pulm Med & TB, New Delhi 110009, India..
    Chopra, Kamal K.
    New Delhi TB Ctr, New Delhi 110002, India..
    Sharma, Nandini
    Maulana Azad Med Coll, Dept Community Med, New Delhi, India..
    Khanna, Ashwani
    Lok Nayak Hosp Chest Clin, New Delhi 110002, India..
    Chowdhury, Jayeeta
    Tata Trusts, Mumbai 400001, Maharashtra, India..
    Stoner, Robert
    MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Energy Initiat, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Slocum, Alexander H.
    MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Cima, Michael J.
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Furin, Jennifer
    Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA 02115 USA..
    Langer, Robert
    MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Media Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Tata Ctr Technol & Design, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Med Sch, Div Gastroenterol Hepatol & Endoscopy, Brigham & Womens Hosp, Boston, MA 02115 USA.;MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment2019In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 11, no 483, article id eaau6267Article in journal (Refereed)
    Abstract [en]

    Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.

  • 20.
    Wang, Xiaojing
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Bleiker, Simon J.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Edinger, Pierre
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Errando-Herranz, Carlos
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Gylfason, Kristinn
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Niklaus, Frank
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Wafer-Level Vacuum Sealing by Transfer Bonding of Silicon Caps for Small Footprint and Ultra-Thin MEMS Packages2019In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 28, no 3, p. 460-471Article in journal (Refereed)
    Abstract [en]

    Vacuum and hermetic packaging is a critical requirement for optimal performance of many micro-electro-mechanical systems (MEMS), vacuum electronics, and quantum devices. However, existing packaging solutions are either elaborate to implement or rely on bulky caps and footprint-consuming seals. Here, we address this problem by demonstrating a wafer-level vacuum packaging method featuring transfer bonding of 25-μm-thin silicon (Si) caps that are transferred from a 100-mm-diameter silicon-on-insulator (SOI) wafer to a cavity wafer to seal the cavities by gold-aluminum (Au-Al) thermo-compression bonding at a low temperature of 250 °C. The resulting wafer-scale sealing yields after wafer dicing are 98% and 100% with sealing rings as narrow as 6 and 9 μm, respectively. Despite the small sealing footprint, the Si caps with 9-μm-wide sealing rings demonstrate a high mean shear strength of 127 MPa. The vacuum levels in the getter-free sealed cavities are measured by residual gas analysis to be as low as 1.3 mbar, based on which a leak rate smaller than 2.8x10-14 mbarL/s is derived. We also show that the thickness of the Si caps can be reduced to 6 μm by post-transfer etching while still maintaining excellent hermeticity. The demonstrated ultra-thin packages can potentially be placed in between the solder bumps in flip-chip interfaces, thereby avoiding the need of through-cap-vias in conventional MEMS packages.

1 - 20 of 20
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