Enabling standardized point-of-care tuberculosis diagnostics via rapid osmotic concentration

通过快速渗透浓度实现标准化床旁结核病诊断

• 批准号: 10697134
• 负责人: James Lai
• 金额: $ 27.26万
• 依托单位: TRULY TECHNOLOGIES LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697134
• 关键词: 2019-nCoV; Address; Affect; Antigens; Area; Award; Biological Assay; Biological Markers; Buffers; Businesses; Centrifugation; Cessation of life; Clinical; Collaborations; Collection; Data; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diffusion; Disease; Enzyme-Linked Immunosorbent Assay; Equation; Equipment; Excision; Exhibits; Grant; Healthcare; Human; Human Chorionic Gonadotropin; Immunoassay; Individual; Industry; Interview; Kinetics; Laboratories; Letters; Mainstreaming; Marketing; Mass Spectrum Analysis; Measures; Membrane; Methods; Microscopy; Modeling; Monitor; Noise; Nucleic Acid Amplification Tests; Nucleocapsid Proteins; Osmosis; Performance; Persons; Phase; Polymers; Power Sources; Preparation; Procedures; Process; Production; Proteins; Recovery; Research; Resource-limited setting; Risk; Sampling; Scientist; Signal Transduction; Small Business Innovation Research Grant; Solubility; South Africa; Special Equipment; Specimen; Speed; Sputum; Standardization; Surface; Temperature; Testing; Therapeutic; Time; Training; Tuberculosis; Ultracentrifugation; Ultrafiltration; Urea; Urea Nitrogen; Urine; With laterality; commercialization; cost; design; detection limit; diagnostic biomarker; diagnostic value; experience; flexibility; improved; infection risk; innovation; lateral flow assay; lipoarabinomannan; manufacturing scale-up; mycobacterial; point of care; point of care testing; point-of-care diagnostics; prevent; prototype; scale up; small molecule; success; tuberculosis diagnostics; tuberculosis treatment; urinary

PROJECT SUMMARY/ABSTRACT Urine is an attractive biospecimen for point-of-care diagnostics because it can be collected in large quantities with noninvasive procedures. Urine-based lateral flow assays (LFAs) are low-cost devices suitable for point-of-care testing, particularly in low-resource settings. However, many urine-based LFAs exhibit sensitivity levels well below diagnostic utility due to the low concentration of diagnostic biomarkers present in urine. This is the case with LFAs for tuberculosis (TB) diagnostics and is a major barrier to rapid TB testing and treatment in endemic areas. Mainstream clinical and laboratory tests for diagnosing active TB, including bacterial culture, sputum smear microscopy and nucleic acid amplification tests, present limitations in speed, sensitivity, accessibility, respectively. These tests also require sputum samples that present additional difficulty and exposure risks for healthcare staff during the collection procedure. To address this, we developed an osmotic processor that statically and spontaneously concentrates urinary biomarkers for use in LFAs. Urea and small molecules that can interfere with downstream assays are removed in the concentration process. Using human chorionic gonadotropin (hCG) protein as a model analyte, we showed near 100-fold concentration of a 20 mL sample in an early prototype. By exploiting the principles of osmosis, recent prototypes developed by the company show promise in significantly reducing processing time to within 30 minutes. With its simplicity and flexibility, the device demonstrates a great potential to be interfaced with existing LFAs to enable highly sensitive detection of dilute target analytes in urine, while still retaining a diagnostic time suitable for point-of-care diagnostics. The project aims to validate molecule concentration quantitatively with mass spectrometry in newer prototypes, perform spike-and-recovery tests with simulated urine and lab-based LAM, and then test qualitatively with TB-positive clinical samples and LFAs. If awarded the Phase I SBIR grant, the team will hire another full time research scientist, register our device as a General Controls Device through the FDA, continue business collaborations with companies developing LFAs, research other applications of the device to process other biomarkers for diagnostic, disease monitoring and therapeutic purposes, and plan scale-up of device production for commercial distribution in preparation of Phase II.

项目摘要/摘要 尿液是用于护理点诊断的有吸引力的生物测量，因为可以大量收集 使用无创程序。基于尿液的侧向流程分析（LFAS）是适合的低成本设备 护理点测试，尤其是在低资源设置中。但是，许多基于尿液的LFA表现出敏感性 由于尿液中存在的诊断生物标志物浓度低，远低于诊断效用。这 LFA是结核病（TB）诊断的情况，是快速结核测试和治疗的主要障碍 在流行地区。主流临床和实验室测试，用于诊断活性结核，包括细菌培养， 痰涂片显微镜和核酸扩增测试，速度，灵敏度的当前限制， 分别可访问性。这些测试还需要痰液样品，这些样本会带来额外的困难，并且 在收集程序期间，医疗人员的接触风险。 为了解决这个问题，我们开发了一个从静态和自发浓缩尿液的渗透处理器 用于LFA的生物标志物。尿素和可能干扰下游测定的小分子被去除 在集中过程中。将人绒毛膜促性腺激素（HCG）蛋白作为模型分析物，我们 在早期原型中显示了20 mL样品的浓度接近100倍。通过利用原则 渗透性，该公司最近开发的原型表明，有望大大减少处理时间 到30分钟内。该设备具有简单性和灵活性，具有接口的巨大潜力 使用现有的LFA，可以高度敏感地检测尿液中的稀释靶分析物，同时仍保留 适用于护理点诊断的诊断时间。该项目旨在验证分子浓度 在较新的原型中，用质谱法进行定量，对模拟进行尖峰和恢复测试 尿液和基于实验室的LAM，然后用TB阳性临床样品和LFA进行定性测试。 如果授予I期SBIR Grant，该团队将聘请另一位全职研究科学家，将我们的设备注册为 通用控制设备通过FDA，继续与开发公司的公司进行业务合作 LFA，研究该设备处理其他生物标志物进行诊断，疾病监测的其他应用 以及治疗目的，并计划设备生产的规模，以准备商业分销 第二阶段。