Early Detection of Bladder Cancer Using a Waveguide Array Biosensor

描述(申请人提供)：膀胱癌(BC)是世界范围内的一个主要健康问题。据估计，在美国，2012年有73,510名男性和女性被诊断患有BC，14,880人死于这种疾病。通常，癌症的早期诊断可以提高存活率，并使最佳风险评估成为可能。诊断BC的一个主要问题是缺乏与该疾病相关的明显症状，因此有必要依靠医学检测。为了解决这个问题，物理光学公司(POC)建议开发一种用于膀胱癌早期诊断的波导阵列式生物传感器(WABS)。WABS系统基于建立在集成光学芯片(IOC)上的长周期光栅(LPG)阵列，该集成光学芯片(IOC)覆盖有对应于一组膀胱癌尿液生物标志物的捕获抗体。WABS是一种混合结构，将光学芯片安装在硅衬底上。该生物传感器是利用微电子机械系统(MEMS)技术制造的。该传感器将快速、准确地评估尿样中是否存在膀胱癌的多个尿蛋白生物标志物。WABS由光波导、边缘贴装激光二极管(LD)和光电探测器(PD)组成。在LiNbO_3芯片上制造的光波导将被微机械加工到硅上的应变消除柱的顶部与硅结合。我们将在电子学中嵌入人工神经网络(ANN)算法，这将显著提高生物标志物检测的准确性。WABS系统将是一种无标签、一步式、点式筛查工具，用于膀胱癌的早期检测，并将提供一种有吸引力的替代侵入性诊断的方法 膀胱镜检查等方法。在第一阶段，WABS系统将设计为最佳的灵敏度和检测极限。该系统将装配一个微流控模块，用于处理非常低的样本量(&lt；10毫升)。POC将通过制造组件、组装原型并展示其对人工尿样中添加的NMP22、Lewis X、BTA、UPK3A和BLCA-4等多种BC生物标志物进行无标记识别和定量的能力，来证明WABS系统的可行性。在第二阶段，WABS系统将扩大，实现对几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、自动数据分析和针对大规模生产潜力的低制造成本。这项第一阶段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.