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

描述（由申请人提供）：在该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的新工具。该工具允许从活细胞的机械和热特性测量有关细胞过程的信息。到目前为止，还没有一个私人实体集中精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。该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的单细胞疾病标记物的新方法。探头将在水性环境中工作，并将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（用于热性能测量，如热导率和电导率测量，以根据其热特征识别样品）。在本提案中，将解决关键的工程和应用挑战。设计并开发微机械扫描压热探针、接口电路及专用软件。最后，该系统的效用将被证明通过产生热和地形图像的细胞和健康和患病细胞之间的热和粘弹性的歧视。该SBIR是PicoCal，Inc.，Dep.密歇根州立大学电气工程系和部门。密歇根州立大学医学、药理学和毒理学系。这项工作将继续到第二阶段，目的是缩放系统并显着提高扫描速率，以创建一个用于时间和高通量成像的工具。保留字：细胞生物力学、粘弹性、细胞骨架、压痕、刚度、疾病标志物、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、机械转导、机械生物学随着新药开发和批准的临床试验费用在数十亿美元范围内，单细胞疾病标记物提供了一种廉价的方法，在动物或人类上测试药物之前，在活的人类细胞上快速且无害地测试可能的候选药物。与此同时，在单个活细胞上测试的新的个性化治疗方法，而不是像化疗这样的一刀切的治疗方法，在未来很有可能有效地治疗疾病。拟议的仪器可能有助于理解细胞机制和生物学，并可能对疾病敏感，允许使用这种测量作为疾病标志物。这种方法可能会发现临床用途，并可能会增加疾病的识别，鉴定和治疗。

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.