Cancer Detection via Enzymatic Microassays

通过酶微分析检测癌症

• 批准号: 7007698
• 负责人: BRIAN J SULLIVAN
• 金额: $ 37.5万
• 依托单位: KUMETRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7007698
• 关键词: acid phosphatase; bioassay; biomarker; computer simulation; diagnosis design /evaluation; diffusion; electrochemistry; electrodes; enzyme activity; enzyme substrate; method development; microprocessor /microchip; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; prostate neoplasms; protein tyrosine phosphatase; silicon

DESCRIPTION (provided by applicant): New methods for easy, rapid enzymatic assays in very small (sub-microliter) sample volumes will greatly benefit the prognosis, diagnosis, and detection of cancer, in that many cancer markers are enzymes. Currently, the blood sample must be transported to a clinical laboratory for assay, requiring enzyme storage stability, a problem for some enzymes including prostatic acid phosphatase (PAP). Although assay of prostatic specific antigen has largely replaced PAP for initial diagnosis, PAP is still used for staging, and can be used in the developing world for point-of-care diagnosis by unskilled personnel with the proposed technique. Phase I demonstrated the feasibility of adapting silicon microsampling and assay devices, originally developed for diabetic blood glucose monitoring, to enzyme activity measurement, using PAP as the example enzyme. This work is significant because the novel technique employed, diffusive enzyme activity measurement, is a general method adaptable to assaying a wide range of medically important enzymes. Phase II will develop a complete system for PAP assay and will perform simulations to assess its extension to other enzymes having different kinetic constants. The product emerging from this work will be a hand-held instrument capable of accepting single-use disposables to measure the enzymatic activity of PAP. The disposable has a silicon microneedle chip that draws the very small sample easily and reliably, and performs an on-chip assay without further liquid transfer. This system has no on-chip biologicals, and thus can be stored for long periods at ambient temperature.

描述（由申请人提供）：在非常小（亚微升）的样品体积中进行简单、快速的酶测定的新方法将极大地有利于癌症的预后、诊断和检测，因为许多癌症标志物是酶。 目前，血液样品必须运送到临床实验室进行测定，需要酶的储存稳定性，这对于包括前列腺酸性磷酸酶（PAP）在内的一些酶是个问题。虽然前列腺特异性抗原的测定在很大程度上取代了PAP用于初步诊断，但PAP仍用于分期，并且可以在发展中国家由不熟练的人员使用所提出的技术进行即时诊断。第一阶段证明了适应硅微取样和测定装置，最初开发的糖尿病血糖监测，酶活性测量的可行性，使用PAP作为示例酶。这项工作是有意义的，因为新的技术，扩散酶活性测量，是一种通用的方法，适用于测定广泛的医学重要的酶。第二阶段将开发一个完整的PAP测定系统，并将进行模拟，以评估其扩展到其他酶具有不同的动力学常数。这项工作产生的产品将是一种手持式仪器，能够接受一次性使用的一次性用品，以测量PAP的酶活性。该一次性产品具有硅微针芯片，可以轻松可靠地抽取非常小的样本，并在无需进一步液体转移的情况下进行芯片上分析。该系统没有芯片上的生物制剂，因此可以在环境温度下长时间储存。