Smartphone Enabled Point-of-Care Detection of Serum Markers of Liver Cancer

智能手机支持肝癌血清标志物的即时检测

• 批准号: 9933547
• 负责人: Nelson J. Chao
• 金额: $ 68.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9933547
• 关键词: Academic Medical Centers; Affect; Antibodies; Area; Bedside Testings; Binding; Biological Assay; Biological Markers; Biopsy; Blood; Blood Tests; Blood specimen; Cancer Detection; Cancer Diagnostics; Cancer Etiology; Cancer Patient; Cancer Prognosis; Care Technology Points; Cellular Phone; Cessation of life; China; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Country; Detection; Development; Devices; Diagnosis; Diagnostic; Diffusion; Disease; Drops; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Excision; Exhibits; Film; Fingers; Gold; Healthcare; Hepatitis B; Hospitals; Human; Human Resources; Image; Image Analysis; Immunoassay; Infrastructure; Intervention; Investigation; Label; Lesion by Stage; Magnetism; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Medical; Medical center; Methods; Microarray Analysis; Neoplasm Metastasis; Newly Diagnosed; Non-Malignant; Nonmetastatic; Operative Surgical Procedures; Optics; Outcome; Patients; Performance; Phase; Polymers; Primary carcinoma of the liver cells; Reagent; Refrigeration; Research; Research Personnel; Rights; Screening for Hepatocellular Cancer; Screening for cancer; Sensitivity and Specificity; Serum; Serum Markers; Signal Transduction; Spottings; Surface; Taiwan; Technology; Testing; Thinness; Training; Universities; Validation; accurate diagnosis; alpha-Fetoproteins; base; cancer biomarkers; cancer care; cancer diagnosis; chronic liver disease; clinical diagnostics; clinical investigation; cost; detector; direct application; global health; healthy volunteer; high risk population; improved; industry partner; innovation; low and middle-income countries; meetings; osteopontin; point of care; portability; research clinical testing; screening; smartphone Application; tumor; virtual

ABSTRACT Hepatocellular cancer (HCC) is the sixth most common cancer worldwide, and is highly prevalent in low- and middle-income countries (LMIC). China alone accounts for >50% of HCC diagnoses. Surgical removal is the primary and only curative option, yet only 30-40% of newly diagnosed patients are candidates for such treatment. This is because the development of HCC is usually silent and diagnosis occurs relatively late, when the disease has either metastasized or grown too large for surgical removal. Therefore, early diagnosis is the key to achieving positive clinical outcomes, as removal at early-stage —when the tumor is small and not metastatic— would result in a marked increase in cures in affected patients. Motivated by this hypothesis, the objective of this proposal is to develop a blood-based point-of-care test (POCT) for hepatocellular cancer (HCC). The POCT we have developed, the “D4 POCT”, is ideally suited for blood-based testing in LMIC settings. The D4 POCT uses polymer brush-coated antibody (Ab) microarrays that have virtually no background binding, yields quantitative results, and achieves picomolar sensitivity within 30 minutes. All reagents are inkjet-printed and stored on D4 POCT cassettes, which do not require refrigeration. Upon direct application of fingerstick blood onto a cassette, analyte capture and detection occur automatically, generating a quantifiable signal obtained by placing the cassette in a small device that magnetically attaches to a smart phone, which images and analyzes microarrays via on-board App. We will develop a multiplexed D4 POCT capable of simultaneously detecting alpha-fetoprotein (AFP), dickkopf-1 (DKK-1) and osteopontin (OPN) that will provide high sensitivity and specificity for HCC diagnosis. Our choice of markers is based on recent clinical evidence showing that the simultaneous measurement of AFP, DKK-1, and OPN as a multiplexed panel provides a promising strategy for early and accurate diagnosis of HCC. The innovation of this proposal is the first complete bottom-up redesign in decades of the “gold standard” clinical diagnostic—the sandwich immunoassay—as a self-contained point-of-care microarray assay that can be imaged and interrogated by a smart phone. This project will be carried out by a consortium of investigators from Duke University, Zhejiang Provincial People's hospital and our industry partner, Immucor, a leading diagnostics company that has acquired the rights to this technology. After initial validation of the D4 POCT at Duke by meeting specific performance milestones, we will demonstrate technical functionality and clinical potential for use in LMIC settings at the Zhejiang Provincial People's hospital in Guangzhou China using patient-derived finger-stick blood samples. The impact of this project is broad: beyond a new, low-cost, and clinically validated technology for the point-of-care diagnosis of HCC, this diagnostic technology can be utilized to target any analyte for which Ab pairs are available, and is hence broadly applicable to all immunoassays used for diagnosis and prognosis for cancer or other diseases.

抽象的 肝细胞癌（HCC）是全球第六个最常见的癌症，在低和低 - 中等收入国家（LMIC）。仅中国就占HCC诊断的50％。外科手术是 初级和唯一的治疗选择，但只有30-40％的新诊断患者是这种候选人 治疗。这是因为HCC的发展通常是沉默的，并且诊断性相对迟到， 当该疾病转移或长大而无法手术去除时。因此，早期诊断 是实现阳性临床结果的关键，就像在早期阶段去除的那样 - 肿瘤很小并且 不是转移性 - 会导致受影响患者的治疗方法显着增加。由这个假设的动机， 该提案的目的是为肝癌开发基于血液的护理测试（POCT） （HCC）。我们开发的POCT“ D4 POCT”非常适合LMIC中的基于血液的测试 设置。 D4 POCT使用聚合物刷涂层抗体（AB）微阵列几乎没有 背景结合，产生定量结果，并在30分钟内实现皮摩尔灵敏度。全部 试剂是喷墨印刷的，并存储在D4 POCT盒式上，不需要制冷。直接 将指尖血液应用于盒式录音带，分析物捕获和检测会自动发生，产生 通过将盒式放在磁性附着在智能上的小设备中获得的可量化信号 电话，通过板载应用程序图像和分析微阵列。我们将开发多重的D4 POCT 能够简单地检测α-毒素蛋白（AFP），Dickkopf-1（DKK-1）和骨桥蛋白（OPN） 将为HCC诊断提供高灵敏度和特异性。我们选择的标记是基于最近的临床 证据表明，AFP，DKK-1和OPN作为多重面板的简单测量 提供了一种有希望的策略，以早期诊断为HCC。该提议的创新是 “金标准”临床诊断数十年来的第一个完整自下而上的重新设计 - 三明治 免疫测定 - 作为一个独立的护理点微阵列测定法 手机。该项目将由杜克大学的调查员联盟进行 省级人民医院和我们的行业合作伙伴Inmucor，一家领先的诊断公司 获得了该技术的权利。在Duke初步验证D4 POCT之后 性能里程碑，我们将展示在LMIC中使用的技术功能和临床潜力 使用患者衍生的手指刺的智格省人民医院的设置 血液样本。该项目的影响很广：超越了新的，低成本和临床验证 用于HCC的护理点诊断的技术，该诊断技术可用于针对任何 可用AB对的分析物，因此广泛适用于所有用于的免疫测定 癌症或其他疾病的诊断和预后。