Novel single cell disease markers with a hybrid AFM scanning piezo-thermal probe

使用混合 AFM 扫描压电热探针的新型单细胞疾病标记物

• 批准号: 7480708
• 负责人: Angelo Gaitas
• 金额: $ 20.08万
• 依托单位: KYTARO, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480708
• 关键词: Address; Anatomy; Animals; Area; Arterial Fatty Streak; Arthritis; Atomic Force Microscopy; Basic Science; Biological; Biological Sciences; Biology; Biomechanics; Biomedical Engineering; Cardiac; Cardiovascular Diseases; Cell Count; Cell physiology; Cells; Cellular biology; Characteristics; Chemicals; Clinical; Clinical Trials; Collaborations; Computer software; Coronary Arteriosclerosis; Cystic Fibrosis; Cytoskeleton; Degenerative polyarthritis; Devices; Diagnosis; Disease; Disease Marker; Doctor of Medicine; Electrical Engineering; Electronics; Elements; Engineering; Environment; Evaluation; Exhibits; Fingerprint; Future; Generations; Glass; Goals; Heating; Human; Hybrids; Image; Imaging Device; Knowledge; Life; Liver Cirrhosis; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Marketing; Measurement; Measures; Mechanics; Medical; Medical Imaging; Medicine; Methods; Michigan; Microscopy; Minor; Modification; Molecular; Muscular Dystrophies; Normal tissue morphology; Numbers; Osteoporosis; Particle Size; Pathology; Performance; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Phase Transition; Pliability; Population; Property; Purpose; Range; Rate; Reaction; Reporting; Research; Research Personnel; Research Proposals; Resolution; Sales; Sampling; Scanning; Scanning Probe Microscopes; Scanning Probe Microscopy; Screening procedure; Shapes; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Source; Specimen; Standards of Weights and Measures; Structure; Surface; System; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Transition Temperature; Ultrasonography; Universities; Ventricular Aneurysm; Wisconsin; Work; aqueous; base; cellular imaging; chemotherapy; clinical application; cost; day; design; drug development; drug discovery; drug testing; improved; insight; instrument; interest; nano; nanomechanics; nanometer; nanorobotics; nanoscale; novel; novel therapeutics; regional difference; research study; response; size; technological innovation; tool; tumor; viscoelasticity

DESCRIPTION (provided by applicant): In this SBIR a powerful new tool for imaging biological samples with sub-nanometer resolution is proposed. This tool allows for information on cellular processes to be measured from the mechanical and thermal properties of living cells. To date there has been no concentrated effort by a private entity to use micromachined piezo-thermal atomic force microscopy probes as single cell disease markers. This SBIR Phase I aims to develop a novel method for single cell disease markers using a hybrid scanning piezo-thermal probe and its associated electronics. The probe will operate in aqueous environments and will include an embedded piezoresistive element (for viscoelastic measurements and z-axis sensing), and a thermal element (for thermal properties measurement such as thermal conductance and conductivity measurements to identify the specimen from its thermal signature). In this proposal key engineering and application challenges will be addressed. Micromachined scanning piezo-thermal probes, an interface circuit, and specialized software will be designed and developed. Finally the utility of the system will be demonstrated by producing thermal and topographical images of cells and by discriminating thermally and viscoelastically between healthy and diseased cells. This SBIR is a collaboration between PicoCal, Inc., the Dep. of Electrical Engineering of Michigan State University, and the Depts. of Medicine and Pharmacology & Toxicology of Michigan State University. This work will continue into Phase II with the aim of scaling the system and dramatically improving the scan rate to create a tool useful for temporal and high throughput imaging. Keywords: Cell biomechanics, viscoelasticity, cytoskeleton, indentation, stiffness, disease markers, scanning thermal microscopy, SThM, atomic force microscopy, AFM, scanning probe microscopy, SPM, conductance measurements, cell biology, nanomechanics, mechanotransduction, mechanobiology With the costs of clinical trials for new drug development and approval in the billion dollar range, single cell disease markers offer an inexpensive way to quickly and harmlessly test possible drug candidates on live human cells before testing the drugs on animals or humans. At the same time new personalized treatments tested on single live cells, rather than one-size-fits-all treatments like chemotherapy, have an excellent likelihood of effectively treating diseases in the future. The proposed instrument may contribute to the understanding of cell mechanisms and biology and may be sensitive to disease allowing for the use of such measurements as disease markers. This method may find clinical use and may add to the recognition, identification, and treatment of disease.

描述（由申请人提供）：在此SBIR中，提出了一种功能强大的新工具，用于成像具有子纳米分辨率的生物样品。该工具允许从活细胞的机械和热特性测量细胞过程的信息。迄今为止，私人实体还没有集中精力使用微机械压电 - 热原子力显微镜显微镜探针作为单细胞疾病标记。该SBIR I期旨在使用混合扫描压电 - 热探针及其相关的电子产品开发一种新型的单细胞疾病标记方法。该探针将在水性环境中运行，并包括一个嵌入式的压电元件（用于粘弹性测量和Z轴感测）和一个热元件（用于热性能测量，例如导热电导和电导率测量，以鉴定来自其热标志的样品）。在此提案中，将解决关键工程和应用程序挑战。将设计和开发微机械扫描压电探针，接口电路和专用软件。最后，将通过产生细胞的热图像和地形图像，并在健康和患病细胞之间进行热和粘膜区分来证明该系统的效用。该SBIR是Dep Picocal，Inc。之间的合作。密歇根州立大学电气工程和部门。密歇根州立大学医学和药理学与毒理学。这项工作将持续到II阶段，目的是扩展系统并大大提高扫描速率，以创建用于时间和高吞吐量成像的工具。关键词：细胞生物力学，粘弹性，细胞骨架，凹痕，僵硬，疾病标志物，扫描热显微镜，STHM，原子力显微镜，AFM，AFM，SPMS SPM，SPM，电导率，电导率，电导率测量，细胞生物学，机械机械型，机械型机械型，机械型机械型，机械型机械型，机械型机构，用于新机械型，机械型机构，用于新的临床机构，用于新的机械界限，用于新的机械工具，用于新的机械界限，用于新的机械工具，范围，单细胞疾病标志物提供了一种廉价的方式，可以在对动物或人类的药物进行测试之前，快速无害地测试活体细胞上可能的候选药物。同时，在单个活细胞上测试的新个性化治疗方法，而不是一种适合所有治疗的方法，例如化学疗法，在将来有效治疗疾病的可能性很高。所提出的仪器可能有助于理解细胞机制和生物学，并且可能对疾病敏感，允许使用诸如疾病标志物等测量。该方法可能会发现临床用途，并可能增加疾病的识别，鉴定和治疗。