Early Detection of Bladder Cancer Using a Waveguide Array Biosensor

使用波导阵列生物传感器早期检测膀胱癌

• 批准号: 8713208
• 负责人: Shelly John Mechery
• 金额: $ 15万
• 依托单位: PHYSICAL OPTICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8713208
• 关键词: Address; Age-Years; Algorithms; Antibodies; Biological Markers; Biological Neural Networks; Biosensor; Bladder Neoplasm; Cancer Patient; Clinical; Consumption; Coupling; Cystoscopy; Cytology; Data Analyses; Detection; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic Neoplasm Staging; Diagnostic Procedure; Diagnostic tests; Disease; Early Diagnosis; Economic Burden; Electronics; Elements; Evaluation; Face; Goals; Government; Health; Healthcare Systems; Hematuria; Hospitals; Household; Hybrids; Image; Label; Laboratories; Lasers; Lead; Light; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measurement; Medical; Methods; Microfluidics; Modeling; Molecular; Monitor; Morbidity - disease rate; National Cancer Institute; One-Step dentin bonding system; Optics; Pain; Patients; Persons; Phase; Physicians; Physicians' Offices; Prevalence; Process; Production; Proteins; Protocols documentation; Recurrence; Research; Risk Assessment; Sampling; Screening for cancer; Severity of illness; Silicon; Survival Rate; Symptoms; System; Technology; Testing; Time; Treatment Efficacy; Tumor Antigens; United States; Urine; Woman; Work; base; cancer recurrence; cancer therapy; cost; design; follow-up; innovation; lithium niobate; men; multiplex detection; operation; phase 1 study; photonics; point of care; point-of-care diagnostics; prototype; public health relevance; rapid detection; response; screening; sensor; tool; urinary

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.

描述（由申请人提供）：膀胱癌（BC）代表了世界上一个主要的健康问题。据估计，在美国，有73,510名男性和女性被诊断出患有卑诗省，2012年有14,880人死于该疾病。通常，早期诊断癌症会提高存活率并实现最佳风险评估。 BC诊断的一个主要问题是缺乏与该疾病相关的不同症状，因此有必要依靠医学测试。为了解决这个问题，物理光学公司（POC）建议开发波导阵列生物传感器（WABS），以早期诊断出膀胱癌。 WABS系统基于建立在集成的光学芯片（IOC）上的长时间光栅（LPG）阵列，该阵列涂有与膀胱癌尿液生物标志物相对应的捕获抗体。 WABS是一种混合结构，其光学芯片安装在硅基板上。生物传感器是使用微电动系统（MEMS）技术制造的。该传感器将对尿液样品中多种膀胱癌的多种尿蛋白生物标志物的存在进行快速准确的评估。 WAB由光学波导，边缘安装的激光二极管（LDS）和光电遗传学（PDS）组成。在LINBO3芯片上制造的光学波导将粘合到硅上的硅上的硅上，该柱微压在硅上。我们将在电子设备中嵌入人工神经网络（ANN）算法，该算法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，护理点筛选工具，用于早期检测膀胱癌，并为侵入性诊断提供有吸引力的替代品 膀胱镜检查等方法。在第一阶段，WABS系统将设计用于最佳灵敏度和检测极限。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，并证明其能够对多种BC生物标记物进行标签鉴定和定量，例如NMP22，如NMP22，Lewis X，BTA，UPK3A，UPK3A和BLCA-4在人工尿液样本中涂有多种BC生物标志物，证明了WABS系统的可行性。在II期中，WABS系统将扩展以实现多种癌症生物标志物的多重检测并使用临床样品进行了测试。该系统还将被优化，以提供旨在大规模生产潜力的快速检测，自动数据分析和低制造成本。这一I阶段研究将导致开发可用于癌症分期的仪器，评估患者对抗癌治疗的反应以及随后的监测。