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（由申请人提供）：撒哈拉以南非洲地区面临的主要挑战之一是艾滋病相关癌症的高患病率（“第二波艾滋病”）。这包括侵袭性淋巴瘤，例如弥漫性大 B 细胞瘤和伯基特氏淋巴瘤，其中相当一部分未得到处理或被错误分类。这是因为病理学服务的瓶颈、获得适当组织标本的机会有限、专家的可用性有限、缺乏 除其他因素外，农村环境中仪器仪表充足。考虑到即使在低收入和中等收入国家（LMIC），很大一部分病例是可以治愈的，因此通常会错过治疗机会。因此，需要低成本、快速且准确的检测技术来正确诊断侵袭性淋巴瘤（和其他常见癌症）。创新。我们开发了一种低成本、简单的基于全息术的分子检测策略，并已在智能手机上实施。本质上，将新鲜收获的细针抽吸物 (FNA) 添加到一次性阵列室中，其中包含具有独特尺寸和吸光度/全息特征的冻干抗体包被的珠子。使用智能手机的内置摄像头对珠子与细胞的结合进行全息测量。捕获的图像被传输到服务器，其中重建算法对图像内容进行解卷积，以提供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、包埋、切片和染色的需要以及免疫病理学家专家解释的需要。事实上，整个手术可以由护士来完成，这在非洲是一个主要优势。我们已将这些创新功能集成到工作智能手机原型中，并测试了该设备在淋巴瘤和宫颈癌中的作用。在这些初步的可行性实验中，我们已经实现了单细胞检测灵敏度以及表型分析能力。该应用程序的目标是推进这一尖端的护理点平台，并将其应用于解决非洲诊断淋巴瘤的挑战。我们提出两个主要目标。在 UH2 阶段，我们将把现有原型扩展到淋巴瘤诊断所必需的多重传感。在 UH3 阶段，我们将在博茨瓦纳进行两项临床试验。在第一项试验（HALT-1 试验）中，我们将招募哈博罗内和弗朗西斯敦的​​ 200 名临床高度怀疑患有淋巴瘤的患者，以将智能手机诊断与传统免疫组织化学进行比较。为了将实用性扩展到农村地区，我们将与最近建立的博茨瓦纳计划合作，该计划支持 30 个农村社区，并对 200 名因不明原因淋巴结病接受细针穿刺活检的患者进行“真实世界”研究（HALT-2 试验）。该合作提案汇集了一个由世界级临床医生、肿瘤学家、创新者、工程师、全球健康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。我们在该提案的两个阶段中提出以下目标。