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A micromachining fluidic cantilever for single cell advanced patch clamping and cellular characterization using atomic force microscopy

使用原子力显微镜进行单细胞先进膜片钳和细胞表征的微加工流体悬臂

基本信息

批准号：
10615901
负责人：
Ami Chand
金额：
$ 80.52万
依托单位：
APPLIED NANOSTRUCTURES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615901
关键词：
Academia Action Potentials Address Adhesives Affect Area Atomic Force Microscopy Biological Biological Assay Biological Markers Biological Sciences Biology Biomedical Research Cardiac Myocytes Cardiology Cardiotoxicity Cell Therapy Cell surface Cells Clinical Consumption Development Devices Disease Doctor of Philosophy Drug Evaluation Elasticity Electrodes Electronics Electrophysiology (science)Endocrinology Event Failure Feedback Functional disorder Genetic Heart Diseases Hour Human In Vitro Individual Industry Ion Channel Ions Laboratories Laboratory Technicians Learning Libraries Marketing Masks Measurement Measures Membrane Potentials Microbiology Microelectrodes Modality Muscle Fibers Nanostructures Nanotechnology Neurology Neurons Neurosciences Patients Performance Pharmaceutical Preparations Pharmaceutical Solutions Pharmacologic Substance Phenotype Population Property Publishing Pump Reaction Records Research Research Personnel Resolution Safety Scanning Probe Microscopes Scientist Small Business Innovation Research Grant Spectrum Analysis Structure of beta Cell of islet System Techniques Technology Testing Time Tissue Sample Toxic effect Training assessment application cantilever consumer demand design drug candidate drug discovery elastography electrical property heart cell heart function improved induced pluripotent stem cell medical schools meter nanomachine novel therapeutics patch clamp personalized medicine pharmacologic response seal sensor tool validation studies viscoelasticity

项目摘要

Single patch clamping is used to multiple areas of biology such as cardiology (cardiomyocytes), neurology/neuroscience (neurons), endocrinology (pancreatic beta cells), myology (muscle fibers), and even microbiology (bacterial ion channels). Applied Nanostructures (AppNano) in partnership with the Icahn School of Medicine is bringing to the market a unique solution addressing a major market need in electrophysiology measurements. With its advanced features and unmatched resolution, the device will enable researchers in academia and in the highly competitive life sciences industry to answer important scientific questions and develop and test new drugs fueling the discovery of new pharmaceutical solutions. As a result, these companies will be better equipped to keep up with the ever-increasing consumer demand for pharmaceutical products. In this SBIR we are developing a semi-automated system based on an micro-electromechanical systems (MEMS) sensor pipette used with atomic force microscopes (AFM) that can measure, simultaneously and directly, electrophysiological properties (such as action potentials (AP)), contractile forces on single cardiomyocytes (CM), and single cell elasticity. This system offers high content analysis (HCA) at a single cell level. The system enables a significant increase in performance and a dramatic decrease in time to complete a measurement. With times <5 min compared to conventional patch clamping (2-4 hours) achieved by leveraging micromachining and advanced atomic force microscopy (force spectroscopy). The proposed system will simplify patch clamping measurements and require minimal training. This system will make it reasonably easy for any laboratory technician to conduct these measurements, in contrast to conventional patch clamping, which has a steep learning curve and requires a PhD-level scientist. In addition to action potential and contraction force, we can also evaluate the viscoelastic and adhesive properties of the cells. Our device will be capable of addressing a critical bottleneck in drug discovery that arises during the final characterization of drug candidates. The device can detect single cell changes that would otherwise be masked when averaged over large populations, offering the advantage of measuring rare events, such as toxicity indicators that affect the beating phenotype or action potential (AP) of subpopulations of CMs. This tool finds applications in: drug evaluation/discovery, in the study of Cardiomyocytes (CM) derived from human induced pluripotent stem cells (CM-iPSCs), as a general patch- clamping tool, and in clinical settings. In the setting of personalized medicine, for example, the tool allows for interrogation of enough iPSC-CM (generated from a patient’s tissue sample for instance) to produce statistically meaningful results within several minutes that would indicate an individual’s reaction to a specific drug. Additionally this tool finds application in the study to other types of cardiotoxic effects and in other fields of biomedical research that use electrophysiology (patch clamping), such as neuroscience/neurology and endocrinology.

单贴片夹紧被用于生物学的多个领域，如心脏病学（心肌细胞），