Early Detection of Bladder Cancer Using a Waveguide Array Biosensor

描述（由申请人提供）：膀胱癌（BC）代表了全世界的主要健康问题。据估计，在美国，73，510名男性和女性被诊断患有BC，2012年有14，880人死于这种疾病。通常，癌症的早期诊断可以提高生存率，并实现最佳的风险评估。BC诊断的一个主要问题是缺乏与疾病相关的明显症状，因此必须依赖医学测试。为了解决这个问题，物理光学公司（POC）提出开发一种用于膀胱癌早期诊断的波导阵列生物传感器（WABS）。WABS系统基于构建在集成光学芯片（IOC）上的长周期光栅（LPG）阵列，该芯片涂覆有与膀胱癌的一组尿液生物标志物相对应的捕获抗体。WABS是一种混合结构，光学芯片安装在硅衬底上。该传感器采用微机电系统（MEMS）技术制造。该传感器将提供尿液样本中膀胱癌的多种尿蛋白生物标志物的存在的快速和准确的评估。WABS由光波导、边缘安装的激光二极管（LD）和光电探测器（PD）组成。在LiNbO3芯片上制造的光波导将被结合到硅上的应变消除柱顶部的硅上。我们将在电子设备中嵌入人工神经网络（ANN）算法，这将显着提高生物标志物检测的准确性。WABS系统将是一种无标签、一步到位的护理点筛查工具，用于膀胱癌的早期检测，并将为侵入性诊断提供一种有吸引力的替代方案。 如膀胱镜检查。在第一阶段，WABS系统将设计为最佳灵敏度和检测限。该系统将与微流体模块组装，用于处理非常低的样品体积（<10 mL）。POC将通过制造组件、组装原型并证明其无标记鉴定和定量多种BC生物标志物（如在人工尿样中加标的NMP 22、刘易斯X、BTA、UPK3A和BLCA-4）的能力来证明WABS系统的可行性。在第二阶段，将扩大WABS系统，以实现多种癌症生物标志物的多重检测，并使用临床样本进行测试。该系统还将进行优化，以提供快速检测，自动数据分析和低制造成本，旨在实现大规模生产的潜力。这项I期研究将导致开发一种可用于癌症分期、评估患者对抗癌治疗的反应以及后续监测的仪器。

DESCRIPTION (provided by applicant): Bladder cancer (BC) represents a major health problem throughout the world. It is estimated that in the United States, 73,510 men and women were diagnosed with BC and 14,880 died of the disease in 2012. Often, early diagnosis of cancer enhances survival rates and enables optimal risk assessment. One major problem for the diagnosis of BC is the lack of distinct symptoms associated with the disease, so it is necessary to rely on medical testing. To address this problem, Physical Optics Corporation (POC) proposes to develop a Waveguide Array Biosensor (WABS) for early diagnosis of bladder cancer. The WABS system is based on a long period grating (LPG) array built on an integrated optical chip (IOC), which is coated with capture antibodies corresponding to a panel of urinary biomarkers of bladder cancer. WABS is a hybrid construction with an optical chip mounted onto a silicon substrate. The biosensor is fabricated using microelectromechanical system (MEMS) technology. The sensor will provide a rapid and accurate assessment of the presence of multiple urinary protein biomarkers of bladder cancer in urine samples. WABS consists of optical waveguides, edge-mounted laser diodes (LDs), and photodetectors (PDs). The optical waveguides, fabricated on a LiNbO3 chip, will be bonded to the silicon on top of strain-relieved posts micromachined onto silicon. We will embed an artificial neural network (ANN) algorithm in the electronics, which will significantly increase the accuracy of biomarker detection. The WABS system will be a label-free, one-step, point-of-care screening tool for the early detection of bladder cancer and will provide an attractive alternative to invasive diagnostic methods such as cystoscopy. In Phase I, the WABS system will be designed for optimal sensitivity and limit of detection. The system will be assembled with a microfluidic module for handling very low sample volumes (<10 mL). POC will demonstrate the feasibility of the WABS system by fabricating components, assembling a prototype, and demonstrating its capability for label-free identification and quantitation of multiple BC biomarkers such as NMP22, Lewis X, BTA, UPK3A, and BLCA-4 spiked in artificial urine samples. In Phase II, the WABS system will be expanded to achieve multiplex detection of several cancer biomarkers and tested using clinical samples. The system will also be optimized to offer rapid detection, automatic data analysis, and low manufacturing cost aimed at the potential for mass production. This Phase I study will lead to the development of an instrument that can be used for cancer staging, assessing a patient's response to anticancer therapy, and subsequent monitoring.