SwePub - search: WFRF:(Roxhed Niclas)

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1.	Abramson, Alex, et al. (author) A luminal unfolding microneedle injector for oral delivery of macromolecules 2019 In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:10, s. 1512- Journal article (peer-reviewed)abstract 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.
2.	Abramson, Alex, et al. (author) An ingestible self-orienting system for oral delivery of macromolecules 2019 In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 363:6427, s. 611- Journal article (peer-reviewed)abstract 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.
3.	Abramson, Alex, et al. (author) Ingestible transiently anchoring electronics for microstimulation and conductive signaling 2020 In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:35 Journal article (peer-reviewed)abstract Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes' successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.
4.	Abramson, Alex, et al. (author) Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors 2021 In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:1, s. 103-109 Journal article (peer-reviewed)abstract Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
5.	Antelius, Mikael, et al. (author) Hermetic integration of liquids in MEMS by room temperature, high-speed plugging of liquid-filled cavities at wafer level 2011 In: Proceedings IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. ; , s. 356-359 Conference paper (other academic/artistic)abstract This paper reports a novel room temperature hermetic liquid sealing process based on wire bonded "plugs" over the access ports of liquid-filled cavities. The method enables liquids to be integrated already at the fabrication stage. Test vehicles were manufactured and used to investigate the mechanical and hermetic properties of the seals. A helium leak rate of better than 1E-10 mbarL/s was measured on the successfully sealed structures. The bond strength of the "plugs" were similar to standard wire bonds on flat surfaces.
6.	Antelius, Mikael, et al. (author) Hermetic integration of liquids using high-speed stud bump bonding for cavity sealing at the wafer level 2012 In: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 22:4, s. 045021- Journal article (peer-reviewed)abstract This paper reports a novel room-temperature hermetic liquid sealing process where the access ports of liquid-filled cavities are sealed with wire-bonded stud bumps. This process enables liquids to be integrated at the fabrication stage. Evaluation cavities were manufactured and used to investigate the mechanical and hermetic properties of the seals. Measurements on the successfully sealed structures show a helium leak rate of better than 10 (10) mbarL s (1), in addition to a zero liquid loss over two months during storage near boiling temperature. The bond strength of the plugs was similar to standard wire bonds on flat surfaces.
7.	Antelius, Mikael, et al. (author) Room-temperature wafer-level vacuum sealing by compression of high-speed wire bonded gold bumps 2011 In: Proceedings IEEE International Conference on Solid-State Sensors, Actuators, and Microsystems (Transducers). - : IEEE. ; , s. 1360-1363 Conference paper (other academic/artistic)abstract This paper reports experimental results of a novel room temperature vacuum sealing process based on compressing wire bonded gold “bumps”, causing a material flow into the access ports of vacuum-cavities. The leak rate out of manufactured cavities was measured over 5 days and evaluated to less than the detection limit, 6×10-12 mbarL/s, per sealed port. The cavities have been sealed at a vacuum level below 10 mbar. The method enables sealing of vacuum cavities at room temperature using standard commercial tools and processes.
8.	Antelius, Mikael, et al. (author) Wafer-Level Vacuum Sealing by Coining of Wire Bonded Gold Bumps 2013 In: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 22:6, s. 1347-1353 Journal article (peer-reviewed)abstract This paper reports on the investigation of a novel room-temperature vacuum sealing method based on compressing wire bonded gold bumps which are placed to partially overlap the access ports into the cavity. The bump compression, which is done under vacuum, causes a material flow into the access ports, thereby hermetically sealing a vacuum inside the cavities. The sealed cavity pressure was measured by residual gas analysis to 8x10(-4) mbar two weeks after sealing. The residual gas content was found to be mainly argon, which indicates the source as outgassing inside the cavity and no measurable external leak. The seals are found to be mechanically robust and easily implemented by the use of standard commercial tools and processes.
9.	Balslev, Soren, et al. (author) Microfluidic dye laser with compact, low-cost liquid dye dispenser 2005 In: Micro Total Analysis Systems 2004. - 0854048960 ; , s. 375-377 Conference paper (peer-reviewed)abstract We present a compact system consisting of a miniaturized fluid dispenser, delivering liquid laser dye to a micro-chip dye laser. This demonstrates the elimination of bulk fluid pumps for a microfluidic system by using a miniaturized, electrically and chemically inert dispenser, capable of delivering very low flow for extended periods of time.
10.	Bleiker, Simon J., et al. (author) High-Aspect-Ratio Through Silicon Vias for High-Frequency Application Fabricated by Magnetic Assembly of Gold-Coated Nickel Wires 2015 In: IEEE Transactions on Components, Packaging, and Manufacturing Technology. - : IEEE Press. - 2156-3950 .- 2156-3985. ; 5:1, s. 21-27 Journal article (peer-reviewed)abstract In this paper, we demonstrate a novel manufacturing technology for high-aspect-ratio vertical interconnects for high-frequency applications. This novel approach is based on magnetic self-assembly of prefabricated nickel wires that are subsequently insulated with a thermosetting polymer. The high-frequency performance of the through silicon vias (TSVs) is enhanced by depositing a gold layer on the outer surface of the nickel wires and by reducing capacitive parasitics through a low-k polymer liner. As compared with conventional TSV designs, this novel concept offers a more compact design and a simpler, potentially more cost-effective manufacturing process. Moreover, this fabrication concept is very versatile and adaptable to many different applications, such as interposer, micro electromechanical systems, or millimeter wave applications. For evaluation purposes, coplanar waveguides with incorporated TSV interconnections were fabricated and characterized. The experimental results reveal a high bandwidth from dc to 86 GHz and an insertion loss of <0.53 dB per single TSV interconnection for frequencies up to 75 GHz.
11.	Caffarel-Salvador, Ester, et al. (author) A microneedle platform for buccal macromolecule delivery 2021 In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:4 Journal article (peer-reviewed)abstract Alternative means for drug delivery are needed to facilitate drug adherence and administration. Microneedles (MNs) have been previously investigated transdermally for drug delivery. To date, drug loading into MNs has been limited by drug solubility in the polymeric blend. We designed a highly drug-loaded MN patch to deliver macromolecules and applied it to the buccal area, which allows for faster delivery than the skin. We successfully delivered 1-mg payloads of human insulin and human growth hormone to the buccal cavity of swine within 30 s. In addition, we conducted a trial in 100 healthy volunteers to assess potential discomfort associated with MNs when applied in the oral cavity, identifying the hard palate as the preferred application site. We envisage that MN patches applied on buccal surfaces could increase medication adherence and facilitate the painless delivery of biologics and other drugs to many, especially for the pediatric and elderly populations.
12.	Dobielewski, Mikolaj, et al. (author) All-in-one sampler for one-step dried blood spot sample collection 2021 In: Proceedings MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 675-676 Conference paper (peer-reviewed)abstract We present the first fully integrated device for one-step Dried Blood Spot (DBS) sampling. We maximize the sample aspiration efficiency by combining the function of skin lancing and sample aspiration in one component, thus minimizing the required incision size and the related pain. Our volunteer study shows reliable collection of 1 µL of blood in under one minute, while significantly lowering the related pain and discomfort, compared to finger-prick sample collection. The collected samples show quality on par with finger-prick capillary blood samples.
13.	Dobielewski, Mikolaj, et al. (author) Blood Cell Quantification on Dry Blood Samples - Towards Patient-CentricComplete Blood Counts (CBC) 2022 In: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. Journal article (peer-reviewed)abstract Background: Performing complete blood counts (CBC) from patients´ homes could have atransformative impact on e-based healthcare. Blood microsampling and sample drying are enablingelements for patient-centric healthcare. The aim of this study is to investigate the potential of dry bloodsamples for image-based cell quantification of red and white blood cells. Methods: A manual samplepreparation method is developed and tested for image-based red and white blood cell counting. Resultsand Conclusion: Dry blood samples enable image-based cell counting of red and white blood cells with agood correlation to gold standard hematology analyzer data (avg. CV < 6.5%, R2 > 0.8), and resolve thebasic morphology of white blood cell nuclei. The presented proof-of-principle study is a first step towardpatient-centric CBCs.
14.	Ericsson, Per, et al. (author) Toward 17µm pitch heterogeneously integrated Si/SiGe quantum well bolometer focal plane arrays 2011 In: Infrared Technology and Applications XXXVII. - : SPIE - International Society for Optical Engineering. ; , s. 801216-1-801216-9 Conference paper (peer-reviewed)abstract Most of today's commercial solutions for un-cooled IR imaging sensors are based on resistive bolometers using either Vanadium oxide (VOx) or amorphous Silicon (a-Si) as the thermistor material. Despite the long history for both concepts, market penetration outside high-end applications is still limited. By allowing actors in adjacent fields, such as those from the MEMS industry, to enter the market, this situation could change. This requires, however, that technologies fitting their tools and processes are developed. Heterogeneous integration of Si/SiGe quantum well bolometers on standard CMOS read out circuits is one approach that could easily be adopted by the MEMS industry. Due to its mono crystalline nature, the Si/SiGe thermistor material has excellent noise properties that result in a state-ofthe- art signal-to-noise ratio. The material is also stable at temperatures well above 450°C which offers great flexibility for both sensor integration and novel vacuum packaging concepts. We have previously reported on heterogeneous integration of Si/SiGe quantum well bolometers with pitches of 40μm x 40μm and 25μm x 25μm. The technology scales well to smaller pixel pitches and in this paper, we will report on our work on developing heterogeneous integration for Si/SiGe QW bolometers with a pixel pitch of 17μm x 17μm.
15.	Feng, P., et al. (author) MEMS 2021 Welcome 2021 In: IEEE International Conference on Micro Electro Mechanical Systems. - : Institute of Electrical and Electronics Engineers Inc.. - 1084-6999. ; 2021-January, s. i-ii Journal article (peer-reviewed)
16.	Fischer, Andreas C., et al. (author) Fabrication of high aspect ratio through silicon vias (TSVs) by magnetic assembly of nickel wires 2011 In: Micro Electro Mechanical Systems (MEMS), 2011 IEEE 24th International Conference on. - : IEEE. - 9781424496327 ; , s. 37-40 Conference paper (peer-reviewed)abstract Three-dimensional (3D) integration of electronics and/or MEMS-based transducers is an emerging technology that vertically interconnects stacked dies using through silicon vias (TSVs). They enable the realization of devices with shorter signal lengths, smaller packages and lower parasitic capacitances, which can result in higher performance and lower costs of the system. This paper presents a novel low-cost fabrication technique for solid metal-filled TSVs using nickel wires as conductive path. The wires are placed in the via hole of a silicon wafer by magnetic self-assembly. This metal filling technique enables through-wafer vias with high aspect ratios and potentially eliminates characteristic cost drivers of the TSV production such as metallization processes, wafer thinning and general issues associated with thin-wafer handling.
17.	Fischer, Andreas C., 1982-, et al. (author) Heterogeneous Integration for Optical MEMS 2010 In: 2010 23RD ANNUAL MEETING OF THE IEEE PHOTONICS SOCIETY. - NEW YORK : IEEE. - 9781424453696 ; , s. 487-488 Conference paper (peer-reviewed)abstract In this paper we present different large-scale heterogeneous integration technologies for optical MEMS that enable the integration of optical MEMS with standard CMOS-based ICs. Examples that are presented include various monocrystalline silicon micro-mirror arrays and infrared bolometer arrays.
18.	Fischer, Andreas C., 1982-, et al. (author) high aspect ratio tsvs fabricated by magnetic self-assembly of gold-coated nickel wires 2012 In: Electronic Components and Technology Conference (ECTC), 2012 IEEE 62nd. - : IEEE conference proceedings. - 9781467319652 ; , s. 541-547 Conference paper (peer-reviewed)abstract Three-dimensional (3D) integration is an emerging technologythat vertically interconnects stacked dies of electronics and/orMEMS-based transducers using through silicon vias (TSVs).TSVs enable the realization of devices with shorter signal lengths,smaller packages and lower parasitic capacitances, which can resultin higher performance and lower costs of the system. Inthis paper we demonstrate a new manufacturing technology forhigh-aspect ratio (> 8) through silicon metal vias using magneticself-assembly of gold-coated nickel rods inside etched throughsilicon-via holes. The presented TSV fabrication technique enablesthrough-wafer vias with high aspect ratios and superior electricalcharacteristics. This technique eliminates common issues inTSV fabrication using conventional approaches, such as the metaldeposition and via insulation and hence it has the potential to reducesignificantly the production costs of high-aspect ratio stateof-the-art TSVs for e.g. interposer, MEMS and RF applications.
19.	Fischer, Andreas C., 1982-, et al. (author) Integrating MEMS and ICs 2015 In: Microsystems & Nanoengineering. - : Springer Science and Business Media LLC. - 2055-7434. ; 1:1, s. 1-16 Review (peer-reviewed)abstract The majority of microelectromechanical system (MEMS) devices must be combined with integrated circuits (ICs) for operation in larger electronic systems. While MEMS transducers sense or control physical, optical or chemical quantities, ICs typically provide functionalities related to the signals of these transducers, such as analog-to-digital conversion, amplification, filtering and information processing as well as communication between the MEMS transducer and the outside world. Thus, the vast majority of commercial MEMS products, such as accelerometers, gyroscopes and micro-mirror arrays, are integrated and packaged together with ICs. There are a variety of possible methods of integrating and packaging MEMS and IC components, and the technology of choice strongly depends on the device, the field of application and the commercial requirements. In this review paper, traditional as well as innovative and emerging approaches to MEMS and IC integration are reviewed. These include approaches based on the hybrid integration of multiple chips (multi-chip solutions) as well as system-on-chip solutions based on wafer-level monolithic integration and heterogeneous integration techniques. These are important technological building blocks for the ‘More-Than-Moore’ paradigm described in the International Technology Roadmap for Semiconductors. In this paper, the various approaches are categorized in a coherent manner, their merits are discussed, and suitable application areas and implementations are critically investigated. The implications of the different MEMS and IC integration approaches for packaging, testing and final system costs are reviewed.
20.	Fischer, Andreas C., 1982-, et al. (author) Low-Cost Through Silicon Vias (Tsvs) With Wire-Bonded Metal Cores And Low Capacitive Substrate-Coupling 2010 In: MEMS 2010. - : IEEE. - 9781424457649 ; , s. 480-483 Conference paper (peer-reviewed)abstract The three-dimensional (3D) integration of electronics and/or MEMS-based transducers is an emerging technology that vertically interconnects stacked dies using through silicon vias (TSVs). They enable the realization of devices with shorter signal lengths, smaller packages and lower parasitic capacitances, which can result in higher performance and lower costs. This paper presents a novel low-cost fabrication technique for metal-filled TSVs using bonded gold-wires as conductive path. In this concept the wires are surrounded by polymer, which acts both as an electrical insulator causing low capacitive coupling towards the substrate and as a buffer for thermo-mechanical stress.
21.	Fischer, Andreas C., 1982-, et al. (author) Low-cost Through Silicon Vias (Tsvs) with wire-bonded metal cores and low capacitive substratecoupling : 2010 In: Proceedings. - Stockholm : -. ; , s. 30-30 Conference paper (peer-reviewed)
22.	Fischer, Andreas C., 1982-, et al. (author) Method for plugging a hole and a plugged hole 2009 Patent (pop. science, debate, etc.)abstract A method for at least partially inserting a plug into a hole, said method comprising the steps of a) providing a at least one substrate with at least one hole wherein said at least one hole has a largest dimension of from 1 μm to 300 μm, b) providing a piece of material, wherein said piece of material has a larger dimension than said at least one hole, c) pressing said piece of material against the hole with a tool so that a plug is formed, wherein at least a part of said piece of material is pressed into said hole, d) removing the tool from the piece of material. There is further disclosed a plugged hole manufactured with the method. One advantage of an embodiment is that an industrially available wire bonding technology can be used to seal various cavities. The existing wire bonding technology makes the plugging fast and cheap.
23.	Fischer, Andreas C., 1982-, et al. (author) Selective electroless nickel plating on oxygen-plasma-activated gold seed-layers for the fabrication of low contact resistance vias and microstructures : 2010 In: Proceedings. - Stockholm : -. ; , s. 86- Conference paper (peer-reviewed)
24.	Fischer, Andreas C., 1982-, et al. (author) Selective electroless nickel plating on oxygen-plasma-activated gold seed-layers for the fabrication of low contact resistance vias and microstructures 2010 In: MEMS 2010. - : IEEE. - 9781424457618 ; , s. 472-475 Conference paper (peer-reviewed)abstract This paper presents a novel technique to selectively deposit nickel by electroless plating on gold seed layers using an oxygen-plasma-activation step. No prior wet surface pre- treatments or metal oxide etches are required. This enables the manufacturing of low-resistance vias for heterogeneous three-dimensional (3D) integration of MEMS but it is also a suitable technique for the fabrication of arbitrary shaped nickel-microstructures using chemically stable and cost-effective electroless nickel plating baths.
25.	Fischer, Andreas C., 1982-, et al. (author) Unconventional applications of wire bonding create opportunities for microsystem integration 2013 In: Journal of Micromechanics and Microengineering. - : IOP publishing. - 0960-1317 .- 1361-6439. ; 23:8, s. 083001- Research review (peer-reviewed)abstract Automatic wire bonding is a highly mature, cost-efficient and broadly available back-endprocess, intended to create electrical interconnections in semiconductor chip packaging. Modern production wire-bonding tools can bond wires with speeds of up to 30 bonds per second with placement accuracies of better than 2 mu m, and the ability to form each wire individually into a desired shape. These features render wire bonding a versatile tool also for integrating wires in applications other than electrical interconnections. Wire bonding has been adapted and used to implement a variety of innovative microstructures. This paper reviews unconventional uses and applications of wire bonding that have been reported in the literature. The used wire-bonding techniques and materials are discussed, and the implemented applications are presented. They include the realization and integration of coils, transformers, inductors, antennas, electrodes, through silicon vias, plugs, liquid and vacuum seals, plastic fibers, shape memory alloy actuators, energy harvesters and sensors.

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