Smartphone for molecular cancer diagnostic in Africa

 描述（由申请人提供）：撒哈拉以南非洲的主要挑战之一是艾滋病相关癌症（“第二波艾滋病”）的高患病率。这包括侵袭性淋巴瘤，如弥漫性大B细胞淋巴瘤和伯基特氏淋巴瘤，其中相当大的比例没有处理或被错误分类。这是因为病理学服务存在瓶颈，获得适当组织标本的机会有限，专家人数有限，缺乏 在农村环境中适当的仪器，除其他因素外。考虑到即使在低收入和中等收入国家也有相当比例的病例是可以治愈的，因此治疗机会的窗口通常被错过。因此，需要低成本、快速和准确的检测技术来正确诊断侵袭性淋巴瘤（和其他流行的癌症）。创新我们开发了一种低成本、简单的基于全息的分子检测策略，该策略已在智能手机上实现。本质上，将新鲜收获的细针抽吸物（FNA）添加到具有独特尺寸和吸光度/全息特征的冻干抗体包被珠的一次性阵列室中。珠与细胞的结合是使用智能手机的内置摄像头全息测量的。捕获的图像被传输到服务器，在服务器中重建算法解卷积图像内容以提供恶性细胞数量和分子亚型的定量测量。这种方法绕过了大的核心或手术活检，包埋，切片和染色的需要，以及专业的免疫病理学家的解释。事实上，整个手术过程都可以由护士完成，这在非洲是一个很大的优势。我们已经将这些创新功能集成到一个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UH 2阶段，我们将扩展现有的原型，以实现淋巴瘤诊断所必需的多重传感。在UH 3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，我们将在哈博罗内和弗朗西斯敦招募200名临床高度怀疑淋巴瘤的患者，以比较智能手机诊断与传统免疫组织化学。为了将该实用程序扩展到农村环境，我们将与最近建立的博茨瓦纳倡议合作，该倡议支持30个农村社区，并对200名将接受FNA治疗病因不明的淋巴结病的患者进行“真实的世界”研究（HALT-2试验）。该合作提案汇集了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-哈佛合作伙伴关系测试该系统。我们在这一建议的两个阶段提出以下目标。

 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.