Smartphone for molecular cancer diagnostic in Africa

非洲用于分子癌症诊断的智能手机

• 批准号: 9308911
• 负责人: BRUCE ALLAN CHABNER
• 金额: $ 49.14万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308911
• 关键词: AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Africa; Africa South of the Sahara; Algorithms; Antibodies; B-Lymphocytes; Benign; Binding; Biological; Biological Assay; Biopsy; Botswana; Burkitt Lymphoma; Bypass; Cancer Diagnostics; Caring; Cell Count; Cell Differentiation process; Cells; Cellular Phone; Cervical Cancer Screening; Cervical dysplasia; Classification; Clinical; Clinical Research; Clinical Trials; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Reagent; Diffuse; Engineering; Enrollment; Environment; Etiology; Evaluation; Fine needle aspiration biopsy; Flow Cytometry; Freeze Drying; Goals; HIV; Harvest; Health; Health Services Accessibility; Health Status; Healthcare; High Prevalence; Holography; Image; Immunohistochemistry; Light; Lymphatic Diseases; Lymphoma; MS4A1 gene; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measurement; Measures; Molecular; Molecular Analysis; Nurses; Oncologist; Operative Surgical Procedures; Pathologist; Pathology; Patient Triage; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Procedures; Process; Public Health; Resources; Rural Community; Sampling; Screening for cancer; Sensitivity and Specificity; Services; Specialist; Specimen; Staining method; Stains; System; TNFRSF8 gene; Technology; Testing; Therapeutic; Tissues; Training; Triage; Validation; Wireless Technology; base; cancer cell; clinically relevant; cost; cost effective; diagnostic accuracy; experimental study; global health; individual patient; innovation; instrumentation; large cell Diffuse non-Hodgkin' s lymphoma; low and middle-income countries; molecular subtypes; point of care; portability; prospective; prototype; public health relevance; reconstruction; research clinical testing; rural setting

 DESCRIPTION (provided by applicant):One of the major challenges in subsaharan Africa is the high prevalence of AIDS related cancers (the "second wave of AIDS"). This includes aggressive lymphomas such as diffuse large B-cell and Burkitt's, a considerable proportion of which are not worked up or are misclassified. This is because of bottlenecks in pathology services, restricted access to proper tissue specimen, limited availability of specialists, lack of adequate instrumentation in rural settings, among other factors. Considering that a good proportion of cases are curable even in low and middle income countries (LMICs), windows of therapeutic opportunities are commonly missed. As a result, there is a need for low-cost, fast and accurate detection technology to correctly diagnose aggressive lymphomas (and other prevalent cancers). Innovation. We have developed a low-cost, simple holography-based molecular detection strategy that has been implemented on smartphones. In essence, freshly harvested fine needle aspirates (FNA) are added to a disposable array chamber with lyophilized antibody coated beads of unique sizes and absorbance/holographic signatures. Bead binding to cells is holographically measured using the smartphone's built-in camera. Captured images are transferred to a server where reconstruction algorithms deconvolute image content to provide quantitative measures of malignant cell numbers and molecular subtypes. This approach bypasses large core or surgical biopsies, the need for embedding, sectioning and staining, and expert immunopathologist interpretation. Indeed, the entire procedure can be carried out by nurses, a major advantage in Africa. We have integrated these innovative features into a working smartphone prototype and have tested the device in lymphoma and cervical cancer. In these preliminary feasibility experiments, we have achieved single cell detection sensitivities as well as phenotyping capabilities. The goal of this application is to advance this cutting-edge point-of-care platform and apply it to address the diagnostic lymphoma challenges in Africa. We propose two major aims. In the UH2 phase we will expand the existing prototype to multiplexed sensing essential for lymphoma diagnostics. In The UH3 phase we will conduct two clinical trials in Botswana. In a first trial (HALT-1 trial) we will enroll 200 patients in Gaborone and Francistown with a high clinical suspicion for lymphoma to compare smartphone diagnostics to conventional immunohistochemistry. To extend the utility to rural settings we will partner with a recently established Botswana initiative that supports 30 rural communities and perform a `real world' study on 200 patients who will have FNA for lymphadenopathy of unknown etiology (HALT-2 trial). The cooperative proposal brings together a new collaborative team of world class clinicians, oncologists, innovators, engineers, global health experts and entrepreneurs to test the system through the existing Botswana-Harvard partnership. We propose the following aims in the two phases of this proposal.

 描述（由适用提供）：子集体非洲的主要挑战之一是与艾滋病相关的癌症的高流行率（“第二波艾滋病”）。这包括侵略性淋巴瘤，例如弥漫性大B细胞和伯基特（Burkitt's），其中一定比例没有解决或被错误分类。这是因为病理服务中的瓶颈，限制了适当的组织标本，专家的可用性有限，缺乏 除其他因素外，在粗糙环境中适当的仪器。考虑到大部分案件即使在低收入和中等收入国家（LMIC）也可以治愈，因此通常会错过理论机会的窗户。结果，需要低成本，快速准确的检测技术正确诊断侵袭性淋巴瘤（以及其他普遍的癌症）。创新。我们已经开发了一种基于智能手机的低成本，简单的基于全息的分子检测策略。从本质上讲，新鲜收获的细针抽吸物（FNA）被添加到一次性阵列室中，带有冻干的抗体涂层珠的独特尺寸和吸光度/全息特征。使用智能手机的内置摄像头测量了与细胞的珠子结合。将捕获的图像转移到服务器中，在该服务器中，重建算法反应图像内容，以提供对恶性细胞数量和分子亚型的定量测量。这种方法绕过了大型核心或手术活检，对嵌入，切片和染色的需求以及专家免疫病理学家的解释。确实，整个程序可以由护士可以执行，这是非洲的主要优势。我们将这些创新功能集成到了工作的智能手机原型中，并在淋巴瘤和宫颈癌中测试了该设备。在这些初步的可行性实验中，我们已经达到了单细胞检测敏感性以及表型能力。该应用程序的目的是推进这个尖端的护理平台，并将其应用于应对非洲诊断性淋巴瘤挑战。我们提出了两个主要目标。在UH2阶段，我们将将现有原型扩展到淋巴瘤诊断必不可少的多路复用灵敏度。在UH3阶段，我们将在博茨瓦纳进行两项临床试验。在第一次试验（HALT-1试验）中，我们将在Gaborone和Francistown招募200名患者，对淋巴瘤的临床可疑性很高，以将智能手机诊断与常规免疫组织化学进行比较。为了将效用扩展到农村环境，我们将与最近建立的博茨纳那一项计划合作，该计划支持30个农村社区，并对200名患有FNA的患者进行“现实世界”研究，这些患者将患有FNA，患有未知病因学的淋巴结瘤（HALT-2试验）。合作提案汇集了一个由世界一流的临床医生，肿瘤学家，创新者，工程师，全球卫生专家和企业家组成的新合作团队，通过现有的博茨瓦纳 - 哈佛大学合作伙伴关系来测试该系统。我们提出了以下目标在本提案的两个阶段。