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Roxhed, Niclas
Publications (10 of 20) Show all publications
Hauser, J., Stemme, G. & Roxhed, N. (2019). A BLOOD HEMATOCRIT TEST STRIP. In: : . Paper presented at IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS). , 32
Open this publication in new window or tab >>A BLOOD HEMATOCRIT TEST STRIP
2019 (English)Conference paper, Published 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.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:kth:diva-250573 (URN)
Conference
IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS)
Note

QC 20190625

Available from: 2019-04-30 Created: 2019-04-30 Last updated: 2019-06-25Bibliographically approved
Verma, M., Vishwanath, K., Eweje, F., Roxhed, N., Grant, T., Castaneda, M., . . . Traverso, G. (2019). A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment. Science Translational Medicine, 11(483), Article ID eaau6267.
Open this publication in new window or tab >>A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment
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2019 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 11, no 483, article id eaau6267Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:kth:diva-251298 (URN)10.1126/scitranslmed.aau6267 (DOI)000461050500004 ()30867322 (PubMedID)2-s2.0-85062832588 (Scopus ID)
Note

QC 20190509

Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-09Bibliographically approved
Abramson, A., Caffarel-Salvador, E., Soares, V., Minahan, D., Tian, R. Y., Lu, X., . . . Traverso, G. (2019). A luminal unfolding microneedle injector for oral delivery of macromolecules. Nature Medicine, 25(10), 1512-+
Open this publication in new window or tab >>A luminal unfolding microneedle injector for oral delivery of macromolecules
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2019 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 10, p. 1512-+Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-262969 (URN)10.1038/s41591-019-0598-9 (DOI)000489166700019 ()31591601 (PubMedID)
Note

QC 20191104

Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-04Bibliographically approved
Hauser, J., Lenk, G., Ullah, S., Beck, O., Stemme, G. & Roxhed, N. (2019). An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots. Analytical Chemistry, 91(11), 7125-7130
Open this publication in new window or tab >>An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots
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2019 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 11, p. 7125-7130Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:kth:diva-254080 (URN)10.1021/acs.analchem.9b00204 (DOI)000470793800027 ()31063366 (PubMedID)2-s2.0-85066116426 (Scopus ID)
Note

QC 20190625

Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Abramson, A., Caffarel-Salvador, E., Khang, M., Dellal, D., Silverstein, D., Gao, Y., . . . Traverso, G. (2019). An ingestible self-orienting system for oral delivery of macromolecules. Science, 363(6427), 611-+
Open this publication in new window or tab >>An ingestible self-orienting system for oral delivery of macromolecules
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2019 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 363, no 6427, p. 611-+Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:kth:diva-244513 (URN)10.1126/science.aau2277 (DOI)000458114200044 ()30733413 (PubMedID)2-s2.0-85061192140 (Scopus ID)
Note

QC 20190402

Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-04-04Bibliographically approved
Last, T. S., Roxhed, N. & Stemme, G. (2019). Demonstration of the first self-sealing aerosol spray nozzle for medical drug delivery. In: Demonstration of first self-sealing aerosol spray nozzle for medical drug delivery: . Paper presented at IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS) (pp. 1-4). , 32
Open this publication in new window or tab >>Demonstration of the first self-sealing aerosol spray nozzle for medical drug delivery
2019 (English)In: Demonstration of first self-sealing aerosol spray nozzle for medical drug delivery, 2019, Vol. 32, p. 1-4Conference paper, Oral presentation with published abstract (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.

Keywords
BioMEMS, drug delivery, fluidic microjet, inertial microfluidics, respiratory tract disease treatment
National Category
Medical and Health Sciences Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-251748 (URN)
Conference
IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS)
Note

QC 20190819

Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-08-19Bibliographically approved
Lenk, G., Ullah, S., Stemme, G., Beck, O. & Roxhed, N. (2019). Evaluation of a Volumetric Dried Blood Spot Card Using a Gravimetric Method and a Bioanalytical Method with Capillary Blood from 44 Volunteers. Analytical Chemistry, 91(9), 5558-5565
Open this publication in new window or tab >>Evaluation of a Volumetric Dried Blood Spot Card Using a Gravimetric Method and a Bioanalytical Method with Capillary Blood from 44 Volunteers
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2019 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 9, p. 5558-5565Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-251867 (URN)10.1021/acs.analchem.8b02905 (DOI)000467642100017 ()30856315 (PubMedID)2-s2.0-85064830845 (Scopus ID)
Note

QC 20190528

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-06-11Bibliographically approved
Wang, X., Bleiker, S. J., Edinger, P., Errando-Herranz, C., Roxhed, N., Stemme, G., . . . Niklaus, F. (2019). Wafer-Level Vacuum Sealing by Transfer Bonding of Silicon Caps for Small Footprint and Ultra-Thin MEMS Packages. Journal of microelectromechanical systems, 28(3), 460-471
Open this publication in new window or tab >>Wafer-Level Vacuum Sealing by Transfer Bonding of Silicon Caps for Small Footprint and Ultra-Thin MEMS Packages
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2019 (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 28, no 3, p. 460-471Article in journal (Refereed) Published
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.

Keywords
Vacuum, hermetic, packaging, sealing, MEMS, ultra-thin package, small footprint, transfer bonding, 3D integration, flip chip, aluminum, gold, thermo-compression bonding.
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-250639 (URN)10.1109/JMEMS.2019.2910985 (DOI)
Funder
EU, Horizon 2020, 780283
Note

QC 20190619

Available from: 2019-04-30 Created: 2019-04-30 Last updated: 2019-09-11Bibliographically approved
Parrilla, M., Cuartero, M., Sanchez, S. P., Rajabi, M., Roxhed, N., Niklaus, F. & Crespo, G. A. (2019). Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection. Analytical Chemistry, 91(2), 1578-1586
Open this publication in new window or tab >>Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection
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2019 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 2, p. 1578-1586Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-243957 (URN)10.1021/acs.analchem.8b04877 (DOI)000456350000049 ()30543102 (PubMedID)2-s2.0-85059747630 (Scopus ID)
Note

QC 20190301

Available from: 2019-03-01 Created: 2019-03-01 Last updated: 2019-03-06Bibliographically approved
Ribet, F., De Luca, E., Ottonello Briano, F., Swillo, M., Roxhed, N. & Stemme, G. (2019). Zero-insertion-loss optical shutter based on electrowetting-on-dielectric actuation of opaque ionic liquid microdroplets. Applied Physics Letters, 115(7), Article ID 073502.
Open this publication in new window or tab >>Zero-insertion-loss optical shutter based on electrowetting-on-dielectric actuation of opaque ionic liquid microdroplets
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2019 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 115, no 7, article id 073502Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
AMER INST PHYSICS, 2019
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-257810 (URN)10.1063/1.5108936 (DOI)000481469900019 ()2-s2.0-85070688345 (Scopus ID)
Note

QC 20190912

Available from: 2019-09-12 Created: 2019-09-12 Last updated: 2019-09-12Bibliographically approved
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