| 1. |
- Decrop, Deborah, et al.
(författare)
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Single-step imprinting of femtoliter microwell arrays allows digital bioassays with attomolar limit of detection
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:12, s. 10418-10426
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Tidskriftsartikel (refereegranskat)abstract
- Bead-based microwell array technology is growing as an ultrasensitive target detection tool. However, dissemination of the technology and its commercial use are hampered by current fabrication methods for hydrophilic-in-hydrophobic microwell arrays, which are either expensive or labour-intensive to manufacture, or which results in low bead seeding efficiencies. In this paper, we present a novel single-step manufacturing method for imprinting cheap and disposable hydrophilic-in-hydrophobic microwell arrays suitable for single-molecule detection. Single-step imprinting of hydrophilic-in-hydrophobic microwell arrays is made possible using an innovative surface energy replication approach by means of a hydrophobic thiol-ene polymer formulation. In this polymer, hydrophobic-moiety-containing monomers self-assemble against the hydrophobic surface of the imprinting stamp, which results in a hydrophobic replica surface after polymerization. After removing the stamp, hydrophilic wells are obtained with the well bottoms consisting of glass substrate. We demonstrate that the hydrophilic-in-hydrophobic imprinted microwell arrays enable successful and efficient self-assembly of individual water droplets and seeding of magnetic beads with loading efficiencies up to 96%. We also demonstrate the suitability of the microwell arrays for the isolation and detection of single-molecules achieving a limit of detection of 17.4 aM when performing a streptavidin-biotin binding assay. The ease of manufacturing demonstrated here is expected to allow translation of digital microwell array technology towards diagnostic applications.
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| 2. |
- Gylfason, Kristinn B., 1978-, et al.
(författare)
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Integration of polymer based microfluidics with silicon photonics for biosensing applications
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light couplin g allows matching the size scale of microfluidics to that of current silicon photonic biosensors.
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| 3. |
- Kemas, Aurino M., et al.
(författare)
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Insulin-dependent glucose consumption dynamics in 3D primary human liver cultures measured by a sensitive and specific glucose sensor with nanoliter input volume
- 2021
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 35:3
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Tidskriftsartikel (refereegranskat)abstract
- The liver plays a central role in glucose homeostasis and hepatic insulin resistance constitutes a key feature of type 2 diabetes. However, platforms that accurately mimic human hepatic glucose disposition and allow for rapid and scalable quantification of glucose consumption dynamics are lacking. Here, we developed and optimized a colorimetric glucose assay based on the glucose oxidase-peroxidase system and demonstrate that the system can monitor glucose consumption in 3D primary human liver cell cultures over multiple days. The system was highly sensitive (limit of detection of 3.5 mu M) and exceptionally accurate (R-2 = 0.999) while requiring only nanoliter input volumes (250 nL), enabling longitudinal profiling of individual liver microtissues. By utilizing a novel polymer, off-stoichiometric thiol-ene (OSTE), and click-chemistry based on thiol-Michael additions, we furthermore show that the assay can be covalently bound to custom-build chips, facilitating the integration of the sensor into microfluidic devices. Using this system, we find that glucose uptake of our 3D human liver cultures closely resembles human hepatic glucose uptake in vivo as measured by euglycemic-hyperinsulinemic clamp. By comparing isogenic insulin-resistant and insulin-sensitive liver cultures we furthermore show that insulin and extracellular glucose levels account for 55% and 45% of hepatic glucose consumption, respectively. In conclusion, the presented data show that the integration of accurate and scalable nanoliter glucose sensors with physiologically relevant organotypic human liver models enables longitudinal profiling of hepatic glucose consumption dynamics that will facilitate studies into the biology and pathobiology of glycemic control, as well as antidiabetic drug screening.
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| 4. |
- Lobov, Gleb, et al.
(författare)
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Electro-optical effects of high aspect ratio P3HT nanofibers colloid in polymer micro-fluid cells
- 2017
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Ingår i: Optics Letters. - : OSA Publishing. - 0146-9592 .- 1539-4794. ; 42:11, s. 2157-2160
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the electro-optical (EO) effect of Poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofibers colloid in a polymer micro-fluidic EO cell. P3HT nanofibers are high aspect ratio semiconducting nanostructures, and can be collectively aligned by an external alternating electric field. Optical transmission modulated by the electric field is a manifestation of the electro-optical effect due to high inner crystallinity of P3HT nanofibers. According to our results, the degree of alignment reaches a maximum at 0.6 V/μm of electric field strength, implying a big polarizability value due to geometry and electrical properties of P3HT nanofibers. We believe that one-dimensional crystalline organic nanostructures have a large potential in EO devices due to their significant anisotropy, wide variety of properties, low actuation voltages, and opportunity to be tailored via adjustment of the fabrication process.
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| 5. |
- Marinins, Aleksandrs, et al.
(författare)
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Light Converting Polymer/Si Nanocrystal Composites with Stable 60-70% Quantum Efficiency and their Glass Laminates
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:36, s. 30267-30272
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Tidskriftsartikel (refereegranskat)abstract
- Thiol-ene polymer/Si nanocrystal bulk hybrids were synthesized from alkyl-passivated Si nanocrystal (Si NC) toluene solutions. Radicals in the polymer provided a co-passivation of “dark” Si NCs, making them optically active and leading to a substantial ensemble quantum yield increase. Optical stability over several months was confirmed. The presented materials exhibit the highest photoluminescence quantum yield (~65%) of any solid-state Si NC hybrid reported to date. The broad tunability of thiol-ene polymer reactivity provides facile glass integration, as demonstrated by a laminated structure. This, together with extremely fast polymerization, makes the demonstrated hybrid material a promising candidate for light converting applications.
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| 6. |
- Rajabi, Mina, et al.
(författare)
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Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.
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| 7. |
- Sandström, Niklas, et al.
(författare)
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Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding
- 2017
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 27:12
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Tidskriftsartikel (refereegranskat)abstract
- Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges makes them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+ parts to other OSTE+ substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+ cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of commercially available QCM biosensor cartridge.
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| 8. |
- Sandström, Niklas, 1981-, et al.
(författare)
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ONE STEP INTEGRATION OF GOLD COATED SENSORS WITH OSTE POLYMER CARTRIDGES BY LOW TEMPERATURE DRY BONDING
- 2011
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Ingår i: 16th IEEE International Conference on Solid-State Sensors, Actuators and Microsystems (IEEE TRANSDUCERS 2011). - : IEEE conference proceedings. - 9781457701573 ; , s. 2778-2781
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Konferensbidrag (refereegranskat)abstract
- We propose and demonstrate a novel one step method to integrate gold coated sensors with cartridges by dry covalent bonding. The cartridges are replica molded in an UV-curable off-stoichiometry thiol-ene (OSTE) polymer, featuring an excess of thiol functional groups that covalently bond to the surface of gold coated sensors upon contact. The method is demonstrated by the integration of a gold coated quartz crystal to a microfludic OSTE cartridge. The resulting bond interface is shown to be completely homogenous and void free and the package is tested successfully to a differential pressure of up to 2 bars. The performance of the biosensor chip is evaluated by measuring the unspecific binding of 0.5% albumin, resulting in a total frequency drop 205 Hz. This approach delivers a simple but rapid high quality integration aiming for the production of robust, low cost and disposable biosensor chips
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| 9. |
- Sandström, Niklas, 1981-, et al.
(författare)
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Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
- 2015
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Ingår i: Journal of Micromechanics and Microengineering. - : Institute of Physics (IOP). - 0960-1317 .- 1361-6439. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars.
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| 10. |
- Shafagh, Reza Zandi, et al.
(författare)
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Bioengineered Pancreas–Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia
- 2022
-
Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; , s. 2203368-2203368
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant glucose homeostasis is the most common metabolic disturbance affecting one in ten adults worldwide. Prediabetic hyperglycemia due to dysfunctional interactions between different human tissues, including pancreas and liver, constitutes the largest risk factor for the development of type 2 diabetes. However, this early stage of metabolic disease has received relatively little attention. Microphysiological tissue models that emulate tissue crosstalk offer emerging opportunities to study metabolic interactions. Here, a novel modular multitissue organ-on-a-chip device is presented that allows for integrated and reciprocal communication between different 3D primary human tissue cultures. Precisely controlled heterologous perfusion of each tissue chamber is achieved through a microfluidic single “synthetic heart” pneumatic actuation unit connected to multiple tissue chambers via specific configuration of microchannel resistances. On-chip coculture experiments of organotypic primary human liver spheroids and intact primary human islets demonstrate insulin secretion and hepatic insulin response dynamics at physiological timescales upon glucose challenge. Integration of transcriptomic analyses with promoter motif activity data of 503 transcription factors reveals tissue-specific interacting molecular networks that underlie β-cell stress in prediabetic hyperglycemia. Interestingly, liver and islet cultures show surprising counter-regulation of transcriptional programs, emphasizing the power of microphysiological coculture to elucidate the systems biology of metabolic crosstalk.
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| 11. |
- Shafagh, Reza Zandi, et al.
(författare)
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E-Beam Nanostructuring and Direct Click Biofunctionalization of Thiol–Ene Resist
- 2018
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 12:10, s. 9940-9946
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Tidskriftsartikel (refereegranskat)abstract
- Electron beam lithography (EBL) is of major importance for ultraminiaturized biohybrid system fabrication, as it allows combining biomolecular patterning and mechanical structure definition on the nanoscale. Existing methods are limited by multistep biomolecule immobilization procedures, harsh processing conditions that are harmful to sensitive biomolecules, or the structural properties of the resulting protein monolayers or hydrogel-based resists. This work introduces a thiol-ene EBL resist with chemically reactive thiol groups on its native surface that allow the direct and selective "click" immobilization of biomolecules under benign processing conditions. We constructed EBL structured features of size down to 20 nm, and direct functionalized the nanostructures with a sandwich of biotin and streptavidin. The facile combination of polymer nanostructuring with biomolecule immobilization enables mechanically robust biohybrid components of interest for nanoscale biomedical, electronic, photonic, and robotic applications.
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| 12. |
- Shafagh, Reza Zandi, et al.
(författare)
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Facile Nanoimprinting of Robust High-Aspect-Ratio Nanostructures for Human Cell Biomechanics
- 2020
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 3:12, s. 8757-8767
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Tidskriftsartikel (refereegranskat)abstract
- High-aspect-ratio and hierarchically nanostructured surfaces are common in nature. Synthetic variants are of interest for their specific chemical, mechanic, electric, photonic, or biologic properties but are cumbersome in fabrication or suffer from structural collapse. Here, we replicated and directly biofunctionalized robust, large-area, and high-aspect-ratio nanostructures by nanoimprint lithography of an off-stoichiometric thiol–ene-epoxy polymer. We structured—in a single-step process—dense arrays of pillars with a diameter as low as 100 nm and an aspect ratio of 7.2; holes with a diameter of 70 nm and an aspect ratio of >20; and complex hierarchically layered structures, all with minimal collapse and defectivity. We show that the nanopillar arrays alter mechanosensing of human hepatic cells and provide precise spatial control of cell attachment. We speculate that our results can enable the widespread use of high-aspect-ratio nanotopograhy applications in mechanics, optics, and biomedicine.
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| 13. |
- Shen, J. X., et al.
(författare)
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3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis
- 2021
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:16
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and type 2 diabetes are strongly associated with adipose tissue dysfunction and impaired adipogenesis. Understanding the molecular underpinnings that control adipogenesis is thus of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold-free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi-omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R2 = 0.97). Integration of multi-omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis.
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| 14. |
- Shen, J. X., et al.
(författare)
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Organotypic and Microphysiological Models of Liver, Gut, and Kidney for Studies of Drug Metabolism, Pharmacokinetics, and Toxicity
- 2020
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 33:1, s. 38-60
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive breakthroughs in chemistry, molecular biology, and genetics in the last decades, the success rates of drug development projects remain low. To improve predictions of clinical efficacy and safety of new compounds, a plethora of 3D culture methods of human cells have been developed in which the cultured cells retain physiologically and functionally relevant phenotypes for multiple weeks. Here, we critically review current paradigms for organotypic cultures of human liver, gut, and kidney such as perfused microchips, spheroids, and hollow fiber bioreactors and discuss their utility for understanding drug pharmacokinetics, metabolism, and toxicity. Furthermore, bioprinting and the microfluidic integration of different tissue models to mimic systemic drug effects are highlighted as promising technological trends. In the last part of the review, we discuss important considerations regarding the choice of culture substratum material to limit adverse effects such as drug absorption while facilitating the phenotypic maintenance of cultured cells. We conclude that recent advances in organotypic and microphysiological culture models of human tissues can improve drug development and contribute to an amelioration of clinical attrition rates. However, further validation, benchmarking, and consolidation efforts are needed to achieve more widespread dissemination and eventually regulatory acceptance of these novel tools.
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| 15. |
- Youhanna, S., et al.
(författare)
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Organotypic and Microphysiological Human Tissue Models for Drug Discovery and Development—Current State-of-the-Art and Future Perspectives
- 2022
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Ingår i: Pharmacological Reviews. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0031-6997 .- 1521-0081. ; 74:1, s. 141-206
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Tidskriftsartikel (refereegranskat)abstract
- The number of successful drug development projects has been stagnant for decades despite major breakthroughs in chemistry, molecular biology, and genetics. Unreliable target identification and poor translatability of preclinical models have been identified as major causes of failure. To improve predictions of clinical efficacy and safety, interest has shifted to three-dimensional culture methods in which human cells can retain many physiologically and functionally relevant phenotypes for extended periods of time. Here, we review the state of the art of available organotypic culture techniques and critically review emerging models of human tissues with key importance for pharmacokinetics, pharmacodynamics, and toxicity. In addition, developments in bioprinting and microfluidic multiorgan cultures to emulate systemic drug disposition are summarized. We close by highlighting important trends regarding the fabrication of organotypic culture platforms and the choice of platform material to limit drug absorption and polymer leaching while supporting the phenotypic maintenance of cultured cells and allowing for scalable device fabrication. We conclude that organotypic and microphysiological human tissue models constitute promising systems to promote drug discovery and development by facilitating drug target identification and improving the preclinical evaluation of drug toxicity and pharmacokinetics. There is, however, a critical need for further validation, benchmarking, and consolidation efforts ideally conducted in intersectoral multicenter settings to accelerate acceptance of these novel models as reliable tools for translational pharmacology and toxicology. Significance Statement Organotypic and microphysiological culture of human cells has emerged as a promising tool for preclinical drug discovery and development that might be able to narrow the translation gap. This review discusses recent technological and methodological advancements and the use of these systems for hit discovery and the evaluation of toxicity, clearance, and absorption of lead compounds.
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| 16. |
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| 17. |
- Zandi Shafagh, Reza, et al.
(författare)
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NanoRIM : Sub-micron Structuring with Reaction Injection Molding
- 2017
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Ingår i: 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- We report “nanoRIM”, the first reaction injection molding (RIM) replication method for thermosets with demonstrated feature sizes down to 250 nm. NanoRIM constitutes the first scalable manufacturing method for thermoset polymers that allows combining large (> cm) and small (< μm) lateral feature sizes with varying replica thickness in the same device. We demonstrate nanoRIM for manufacturing replica in off-stoichiometry thiol-ene (OSTE) thermoset.
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| 18. |
- Zandi Shafagh, Reza, et al.
(författare)
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Reaction Injection Molding of Hydrophilic-in-Hydrophobic Femtolitre-Well Arrays
- 2019
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Ingår i: Microsystems & Nanoengineering. - : Nature Publishing Group. - 2055-7434. ; :5
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Tidskriftsartikel (refereegranskat)abstract
- Patterning of micro- and nanoscale topologies and surface properties of polymer devices is of particular importance for a broad range of life science applications, including cell-adhesion assays and highly sensitive bioassays. The manufacturing of such devices necessitates cumbersome multiple-step fabrication procedures and results in surface properties which degrade over time. This critically hinders their wide-spread dissemination. Here, we simultaneously mold and surface energy pattern microstructures in off-stoichiometric thiol-ene by area-selective monomer self-assembly in a rapid micro-reaction injection molding cycle. We replicated arrays of 1,843,650 hydrophilic-in-hydrophobic femtolitre-wells with long-term stable surface properties and magnetically trapped beads with 75% and 87.2% efficiency in single- and multiple-seeding events, respectively. These results form the basis for ultrasensitive digital biosensors, specifically, and for the fabrication of medical devices and life science research tools, generally.
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| 19. |
- Zandi Shafagh, Reza
(författare)
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Thiol-ene Nanostructuring
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Improving the health and well-being of humankind does not only constitutepart of our moral codes, but is also enlisted as the number three goal ofthe 2030 agenda for sustainable development set by the UN. Fulfilling suchobjective in the regions of resource-poor settings or for age groups with morevulnerability to infectious agents demands immediate actions. This has necessitatednovel ways of rapid and ultra-sensitive diagnostics to provide compactand affordable systems, e.g. for an early detection of bacteria and viruses.The fields of bio-micro/nanoelectromechanical systems (BioMEMS/NEMS)and lab-on-a-chip (LoC) have been founded based on such demands, butcritically challenged by problems partly associated with manufacturing andmaterial domains and biosensing methods. The fabrication methods for theminiaturization of features and components are often complicated and expensive,the commonly used materials are typically not adaptable to industrialsettings, and the sensing mechanisms are sometimes not sensitive enough forthe detection of lowly-concentrated samples.In this thesis, new methods of ultra-miniaturization, as well as conventionalcleanroom-based techniques, for nanopatterning of well-defined topographiesin off-stoichiometry thiol-ene-(epoxy) polymers are presented. In addition,their use for several sensing applications has been demonstrated. Thefirst part of the thesis gives an introduction to the field of BioMEMS/NEMS.The second part of the thesis presents a technical background about theprevalent methods of polymer micro- and nanofabrication, implementationof the resulting polymer structures for different sensing applications, alongwith the existing challenges and shortcomings associated with state of theart. The third part of the thesis presents e-beam nanostructuring of thiol-eneresist, for the first time, achieving the smallest and densest features reportedin these polymer networks. The thiol-ene-based polymer also represents anovel class of e-beam resist resulting in structures with reactive surface nature.The fourth part of the thesis demonstrates the use of thiol-ene-epoxysystems for nanoimprint lithography and further shows the structuring ofhigh-aspect-ratio and hierarchical topologies via single-step UV-NIL. The fifthpart of the thesis introduces Micro- and NanoRIM platforms for scalable andoff-cleanroom manufacturing of microfluidic devices and nanostructuring ofmaterials in thiol-ene (-epoxy) systems. The sixth part of the thesis exhibitsthe implementation of the noted nanofabrication methods for differentBioMEMS/NEMS applications including protein nanopatterning, simultaneousmolding and surface energy patterning, ultra-sensitive digital biosensing,and facile quartz crystal microbalance (QCM) sensor packaging.
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