- 3D Printing in Biomedical Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Capillary Electrophoresis Applications
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- Neurobiology and Insect Physiology Research
- Microfluidic and Bio-sensing Technologies
- Advanced Chemical Sensor Technologies
- Cancer Cells and Metastasis
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- Cellular Mechanics and Interactions
- CAR-T cell therapy research
- Receptor Mechanisms and Signaling
- Nanopore and Nanochannel Transport Studies
- Advanced biosensing and bioanalysis techniques
- Advanced Data Storage Technologies
- Digital Rights Management and Security
- Immunotherapy and Immune Responses
- Molecular Junctions and Nanostructures
- Soft Robotics and Applications
- Photoreceptor and optogenetics research
- Microbial Inactivation Methods
- Manufacturing Process and Optimization
University of Washington
2005-2024
Seattle University
2015-2024
University of Idaho
2020
Seattle Children's Hospital
2015
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2009-2014
Fred Hutch Cancer Center
2009-2010
Howard Hughes Medical Institute
1995-2009
Cancer Research Center
2009
Harvard University
1999-2008
Microfluidic automation - the automated routing, dispensing, mixing, and/or separation of fluids through microchannels generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and technology's use demands expert operators. Integrating microfluidic in devices has involved specialized multi-layering bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that emerging as efficient alternative for rapid prototyping...
We have further tested the hypothesis that receptor-mediated modulation of KCNQ channels involves depletion phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC). used four parallel assays to characterize agonist-induced PLC response cells (tsA or CHO cells) expressing M1 muscarinic receptors: translocation two fluorescent probes for membrane lipids, release calcium from intracellular stores, and chemical measurement acidic lipids. Occupation...
The identification of receptors that detect environmental stimuli lays a foundation for exploring the mechanisms and neural circuits underlying sensation. mouse vomeronasal organ (VNO), which detects pheromones other semiochemicals, has 2 known families chemoreceptors, V1Rs V2Rs. Here, we report third family VNO comprising 5 7 members formyl peptide receptor (FPR) family. Unlike FPRs, function in immune system, these FPRs are selectively expressed neurons patterns strikingly similar to those...
Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns the kinetics and mechanism M1 muscarinic receptor–mediated regulation cloned M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). Receptors, channels, various mutated G-protein subunits, an optical probe for phosphatidylinositol 4,5-bisphosphate (PIP2) were coexpressed by transfection in tsA-201 cells, cells studied whole-cell patch clamp confocal microscopy. Constitutively active forms Gαq Gα11, but not...
The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these conserved primates. To explore this we examined macaque, higher primate phylogenetically close to humans. Here report organization sensory inputs...
We have developed a digitally-manufacturable microfluidic platform that allows for multiplexed drug testing of intact tumor slices.
Abstract Current methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly patient cancer tissue drugs small molecules offer a promising way improve testing, have potential identify best therapy for patients. We developed digitally manufactured microfluidic platform multiplexed testing intact slice cultures, demonstrate use this evaluate responses in cultures from glioma xenografts tumor biopsies....
Cancer drug testing in animals is an extremely poor predictor of the drug's safety and efficacy observed humans. Hence there a pressing need for functional platforms that better predict traditional immunotherapy responses human, live tumor tissue or constructs, at same time are compatible with use mouse to facilitate building more accurate disease models. Since many cancer actions rely on mechanisms depend microenvironment (TME), such should also retain as much native TME possible....
The mammalian olfactory system is able to discriminate among tens of thousands odorant molecules. In mice, each sensed by a small subset the approximately 1000 receptor (OR) types, with one OR gene expressed sensory neuron (OSN). However, sum large repertoire OR–OSN types and difficulties heterologous expression have made it almost impossible analyze odorant-responsiveness across all types. We developed microfluidic approach that allowed us screen over 20 000 single cells at once in...
As preclinical animal tests often do not accurately predict drug effects later observed in humans, most drugs under development fail to reach the market. Thus there is a critical need for functional testing platforms that use human, intact tissues complement studies. To enable future multiplexed delivery of many one small biopsy, we have developed multi-well microfluidic platform selectively treats cuboidal-shaped microdissected or "cuboids" with well-preserved tissue microenvironments. We...
Mammalian nervous system function involves billions of neurons which are interconnected in a multitude neural circuits. Here we describe genetic approach to chart By using an olfactory-specific promoter, selectively expressed barley lectin sensory the olfactory epithelium and vomeronasal organ transgenic mice. The was transported through axons those bulb, transferred bulb with they synapse, cortex. also retrogradely from neuromodulatory brain areas. No evidence could be obtained for adverse...
ABSTRACT Functional assays on intact tumor biopsies can potentially complement and extend genomics-based approaches for precision oncology, drug testing, organs-on-chips cancer disease models by capturing key determinants of therapeutic response, such as tissue architecture, heterogeneity, the microenvironment. Currently, most these rely fluorescent labeling, a semi-quantitative method best suited to be single-time-point terminal assay or labor-intensive immunostaining analysis. Here, we...
Functional assays on intact tumor biopsies can complement genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key therapeutic response determinants, such as tissue architecture, heterogeneity, the microenvironment. Most of these rely fluorescent labeling, a semiquantitative method best suited single-time-point or labor-intensive immunostaining analysis. Here, we report integrated aptamer electrochemical sensors on-chip,...
Abstract Die Entwicklung der weichen Lithographie hat den Weg bereitet für große Fortschritte auf dem Gebiet Mikrofluidik. Allerdings ist die Fertigung und Betrieb von Mikrofluidiksystemen PDMS‐Basis noch immer arbeitsaufwändig. Hinzu kommen sperrige Steuerungssysteme unhandliche Benutzerschnittstellen, was insgesamt Kommerzialisierung dieser Technologie erschwert. Mit 3D‐Druck steht nun eine Technik zur Verfügung, Mikrofluidikelementen ideal geeignet scheint. Dabei verfährt man so, dass im...
Concerns over biosafety, cost, and carrying capacity of viral vectors have accelerated research into physical techniques for gene delivery such as electroporation mechanoporation. Advances in microfabrication made it possible to create high electric fields microscales, resulting more efficient DNA higher cell viability. Continuous-flow microfluidic methods are typically suitable cellular therapies where a large number cells need be transfected under sterile conditions. However, the existing...
We studied modulation of current in human embryonic kidney tsA-201 cells coexpressing rat erg1 channels with M(1) muscarinic receptors. Maximal was inhibited 30% during receptor stimulation, a small positive shift the midpoint activation. Inhibition attenuated by coexpression regulator G-protein signalling RGS2 or dominant-negative protein, G(q), but not N-ethylmaleimide C3 toxin. Overexpression constitutively active form G(q) (but G(13) G(s)) abolished erg current. Hence it is likely that...
ABSTRACT Current methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly patient cancer tissue drugs small molecules offer a promising way improve testing, have potential identify best therapy for patients. We developed digitally-manufactured microfluidic platform multiplexed testing intact slice cultures, demonstrate use this evaluate responses in cultures from glioma xenografts tumor biopsies....
ABSTRACT Current cancer disease models fail to faithfully recapitulate key features of the human tumor microenvironment (TME), such as immune and vascular cells, while simultaneously enabling high-throughput drug tests. We have recently developed a precision slicing method that optimizes yield large numbers cuboidal microtissues (“cuboids”, ∼(400 µm) 3 ) from single biopsy. Here we demonstrate cuboids syngeneic mouse tumors retain complex TME, making them amenable for immunotherapy...
The scarcity of human biopsies available for drug testing is a paramount challenge developing new therapeutics, disease models, and personalized treatments. Microtechnologies that combine the microscale manipulation tissues fluids offer exciting possibility miniaturizing both models workflows on scarce biopsies. Unfortunately, these technologies presently require microfluidic devices or robotic dispensers are not widely accessible. We have rapidly-prototyped an inexpensive platform based...