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，快速的酶分析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，血液样本必须运送到临床实验室进行分析，这需要酶的储存稳定性，这对包括前列腺酸性磷酸酶（PAP）在内的一些酶来说是一个问题。尽管前列腺特异性抗原测定已在很大程度上取代PAP进行初步诊断，但PAP仍用于分期，并可用于发展中国家的护理点诊断，由不熟练的人员使用所提出的技术。第一阶段演示了将最初用于糖尿病血糖监测的硅微采样和分析设备应用于酶活性测量的可行性，以PAP为例酶。这项工作意义重大，因为所采用的新技术，扩散酶活性测量，是一种适用于分析广泛的医学上重要的酶的通用方法。二期将开发完整的PAP检测系统，并将进行模拟，以评估其对具有不同动力学常数的其他酶的扩展。从这项工作中产生的产品将是一种手持式仪器，能够接受一次性使用，以测量PAP的酶活性。该一次性仪器有一个硅微针芯片，可以轻松可靠地提取非常小的样品，并且无需进一步的液体转移就可以在芯片上进行分析。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。