Advanced Human on a Chip Systems for Drug Discovery

用于药物发现的先进芯片人体系统

• 批准号: 9340303
• 负责人: James J Hickman
• 金额: $ 73.56万
• 依托单位: HESPEROS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-09-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9340303
• 关键词: Acute; Adverse effects; Affect; Automation; Biological Markers; Biological Models; Blood; Cardiac; Cardiovascular system; Cell Culture Techniques; Cells; Chemicals; Chronic; Clinical; Community Developments; Consumption; Cosmetics; Databases; Development; Devices; Drug Costs; Drug toxicity; Evaluation; Failure; Formulation; Gastrointestinal tract structure; Goals; Government; Hand; Health; Housing; Human; In Vitro; Individual; Industry; Investigative Techniques; Legal patent; Letters; Liquid substance; Liver; Measurement; Mechanics; Mediation; Methods; Microelectrodes; Microfluidics; Modeling; Molds; Monitor; Motion; Muscle; Muscle function; Musculoskeletal; Myocardium; Nervous system structure; Neuromuscular Junction; Neurons; Organ; Output; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Physiological; Physiology; Positioning Attribute; Printing; Procedures; Process; Production; Proteins; Pump; Quality Control; Safety; Sampling; Serum; Services; Shipping; Skeletal Muscle; Small Business Innovation Research Grant; Stress; System; Techniques; Testing; Time; Tissue Model; Toxic effect; Toxicology; Validation; Vision; Work; base; body system; cantilever; cooking; cost; design; drug candidate; drug development; drug discovery; drug metabolism; innovation; interest; liver function; models and simulation; next generation; non-invasive monitor; novel; nutrient metabolism; operation; pre-clinical; preclinical evaluation; predicting response; predictive modeling; programs; prototype; public health relevance; research clinical testing; residence; response; sensor; skills; small molecule; validation studies

 DESCRIPTION (provided by applicant): Our overall strategy for the company is to utilize microphysiological systems in combination with functional readouts to establish platforms capable of sophisticated analysis of chemicals and drug candidates for toxicity and efficacy during pre-clinical testing, with initial emphasis on predictive toxicity. This is a service based company that is developing low-cost in vitro systems containing a novel "pumpless" microphysiological platform and serum-free medium formulation. The pumpless integrated system, using a rocking motion to pump the cellular medium, reduces the complexity and cost of the fluidic circuit design and simplifies set-up and operation of the device. The system employs microelectrode arrays and cantilever systems that are integrated on chip to allow for noninvasive electronic and mechanical readouts. These functional readouts greatly reduce the number of biomarkers to be monitored for cell health and function in our systems. We have constructed physiological systems that represent cardiac, muscle, neuronal and liver function that are already being evaluated and utilized for testing in Hickman's lab by pharmaceutical and cosmetic companies. We also have functional, prototype system for human neuromuscular junction, and an integrated 4-organ system consisting of cardiac, liver, neuronal and skeletal muscle compartments. These devices are currently under validation studies and are available as a service for use by industry and government and we are negotiating with major pharmaceutical companies now to utilize these systems. However, all current systems are fabricated and assembled by hand and this factor will continue to hinder production of these systems. In this proposal, advanced manufacturing techniques will be utilized and developed to increase rates of fabrication and testing and lower cost by an order of magnitude. We will partner with NIST to develop these advanced manufacturing techniques and take advantage of Hickman's long association with Dr. Michael Tarlov's group in the Biomolecular Measurement Division. These systems will be tested with drugs that have known multi-organ interactions and ones that target single organs and the results will be compared to human clinical responses. In particular, we will determine whether the system would predict semi-quantitative multi-organ responses to chemicals of interest to the pharmaceutical and cosmetic industries. Dr. Shuler has pioneered the "Body-on-a-Chip" system, a realistic multi-organ platform using cell cultures to predict human response to drugs and biologics and will create a next-generation device. Dr. Hickman has developed functional in vitro human physiological systems and integrated them onto the microphysiological platform in serum-free medium formulations.