权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

High Throughput Screening of Pharmaceuticals Targeting Heart Cell Contractile Function

针对心脏细胞收缩功能的药物的高通量筛选

基本信息

批准号：
9347047
负责人：
BRADLEY M PALMER
金额：
$ 20.51万
依托单位：
IONOPTIX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9347047
关键词：
Action Potentials Address Affect Attention Automation Basic Science Bathing Biological Models Calcium Calcium ion Cardiac Cardiac Myocytes Cell physiology Cell-Matrix Junction Cells Characteristics Computer software Contracts Dangerousness Data Analyses Data Collection Detection Devices Electric Stimulation Equipment Exposure to Feasibility Studies Fluorescent Dyes Fourier Transform Goals Grant Heart Heart Diseases Heart Research Human Resources Image Analysis Individual Ions Laboratories Liquid substance Masks Massachusetts Measurement Mechanics Membrane Potentials Methods Microscope Microscopy Morphology Motivation Movement Muscle Muscle Cells Myocardium Pattern Pharmaceutical Preparations Pharmacologic Substance Phase Phenotype Positioning Attribute Preparation Process Regulation Relaxation Reporting Reproducibility of Results Resources Risk Sarcomeres Scanning System Systems Analysis Techniques Toxic effect Treatment Protocols base cost disease phenotype drug development drug discovery drug efficacy fluid flow heart cell heart function high throughput screening innovation ion dynamics light weight novel programs reagent testing response screening statistics two-dimensional unconscious bias

项目摘要

The isolated cardiac myocyte represents the smallest fully functional model system of heart muscle. Cardiac myocytes contract in response to electrical stimulation and are useful to characterize heart function in terms of contractility, calcium ion regulation, and action potential. Currently, the number of cardiac myocytes that can be examined and analyzed using current techniques is on the order of 1 myocyte per 10 min. Higher throughput is required, however, to accommodate faster drug discovery and a growing motivation in basic research toward large scale rapid data collection and analysis. This grant is focused on validating the feasibility of fully-automated identification of non-overlapping viable myocytes and quantification of contractility and calcium ion regulation in at least 100 myocytes in 10 min. In the pharmaceutical setting, this is a significant enhancement in phenotype quantification that expedites assessment of drug efficacy/toxicity and will greatly reduce costs by permitting companies to eliminate more dangerous or marginal compounds. In Aim 1, we will develop a lightweight x-y moveable inverted microscope that will scan a field of isolated cardiac myocytes. The goal of Aim 1 is to identify isolated and viable cardiac myocytes by their morphology and sarcomeric pattern such that at least 100 useable myocytes are identified within 10 min. In Aim 2, a novel image analysis method will quantify position, size, orientation and dynamic characteristics of contraction-relaxation function for all isolated cardiac myocytes within the field of view, again with the goal of 100 myocytes within 10 min. IonOptix is located in Massachusetts and has provided microscopy-based equipment for assessing intracellular calcium regulation and contraction/relaxation function for the last 25 years.

离体心肌细胞是最小的全功能心肌模型系统。