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

基本信息

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
项目类别：
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

项目摘要

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，提出了一种用于以亚纳米分辨率对生物样品进行成像的强大新工具。该工具可以根据活细胞的机械和热特性测量细胞过程的信息。迄今为止，还没有私人实体集中努力使用微机械压电热原子力显微镜探针作为单细胞疾病标记物。 SBIR 第一阶段旨在开发一种使用混合扫描压电热探针及其相关电子器件来检测单细胞疾病标记物的新方法。该探头将在水性环境中运行，并包括一个嵌入式压阻元件（用于粘弹性测量和 z 轴传感）和一个热元件（用于热属性测量，例如热导和电导率测量，以根据其热特征识别样本）。在此提案中，将解决关键的工程和应用挑战。将设计和开发微机械扫描压电热探头、接口电路和专用软件。最后，该系统的实用性将通过产生细胞的热和形貌图像以及通过热和粘弹性区分健康细胞和患病细胞来证明。该 SBIR 是 PicoCal, Inc.、Dep. 之间的合作。密歇根州立大学电气工程系和系。密歇根州立大学医学和药理学与毒理学博士。这项工作将继续进入第二阶段，目的是扩展系统并显着提高扫描速率，以创建可用于瞬时和高通量成像的工具。关键词：细胞生物力学、粘弹性、细胞骨架、压痕、刚度、疾病标记物、扫描热显微镜、SThM、原子力显微镜、AFM、扫描探针显微镜、SPM、电导测量、细胞生物学、纳米力学、力传导、力生物学对于价值数十亿美元的新药开发和批准试验，单细胞疾病标记物提供了一种廉价的方法，可以在动物或动物身上测试药物之前，在活人细胞上快速、无害地测试可能的候选药物。人类。与此同时，在单个活细胞上测试的新的个性化治疗方法，而不是像化疗这样一刀切的治疗方法，很有可能在未来有效治疗疾病。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，允许使用此类测量作为疾病标记。这种方法可能会在临床上得到应用，并可能有助于疾病的识别、鉴定和治疗。