Smartphone for molecular cancer diagnostic in Africa

 描述(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的高流行率(“第二波艾滋病”)。这包括侵袭性淋巴瘤，如弥漫性大B细胞淋巴瘤和伯基特淋巴瘤，其中相当大一部分没有确诊或分类错误。这是因为病理服务的瓶颈、获得适当组织标本的限制、专家的有限可获得性、缺乏 除其他因素外，在农村环境中提供适当的工具。考虑到即使在低收入和中等收入国家也有很大比例的病例是可以治愈的，治疗机会的窗口通常被错过。因此，需要低成本、快速、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，并已在智能手机上实施。实质上，新鲜收获的细针抽吸物(FNA)被添加到一次性阵列室中，其中含有独特大小和吸光度/全息特征的冻干抗体涂层珠。珠子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，在那里重建算法解卷图像内容，以提供恶性细胞数量和分子亚型的定量测量。这种方法绕过了大块的核心或外科活检，不需要包埋、切片和染色，也不需要免疫病理学家的专业解释。事实上，整个过程都可以由护士进行，这在非洲是一大优势。我们已经将这些创新功能集成到智能手机原型中，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，我们已经获得了单细胞检测灵敏度和表型能力。这一应用程序的目标是推进这一尖端的医疗保健点平台，并将其应用于解决非洲诊断淋巴瘤的挑战。我们提出了两个主要目标。在UH2阶段，我们将把现有的原型扩展到淋巴瘤诊断所必需的多路传输传感。在UH3阶段，我们将在博茨瓦纳进行两项临床试验。在第一个试验(HALT-1试验)中，我们将在哈博罗内和弗朗西斯敦招募200名临床疑似淋巴瘤的患者，将智能手机诊断与传统免疫组织化学进行比较。为了将这一实用程序扩展到农村环境，我们将与最近建立的一项博茨瓦纳倡议合作，该倡议支持30个农村社区，并对200名将接受FNA治疗不明原因的淋巴结病的患者进行“现实世界”研究(HALT-2试验)。这项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的合作团队，通过现有的博茨瓦纳-哈佛合作伙伴关系测试该系统。我们在这项提案的两个阶段提出了以下目标。

 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.