Low Cost Laser Diagnostic for CD4+ T Cell Counting

描述（由申请人提供）：该项目的总体目标是开发和商业化一种简单的细胞计数器，用于常规计数CD4细胞，以管理艾滋病毒感染者。HIV-1介导的CD4细胞破坏是HIV-1感染的主要免疫学特征。因此，CD4计数是疾病初始分期、监测抗逆转录病毒治疗以及管理机会性感染的一级和二级预防的关键指标。流式细胞术是目前CD4细胞计数的标准治疗方法。不幸的是，flow是一种基于实验室的中心技术，样品冷链和运输、设备和操作成本使得该技术在艾滋病毒感染率最高的资源有限的环境中成本过高。一种简单的即时护理（POC） CD4计数工具将从根本上改变HIV-1的管理。该项目的第一阶段已经产生了一种低成本的原型仪器，可以为艾滋病毒感染者和健康献血者的全血标本提供快速、准确和可靠的CD4计数。在这一成功的基础上，我们建议通过最大限度地减少用户与设备的交互来完成技术开发，朝着FDA clia豁免系统的方向发展。具体目标是：

DESCRIPTION (provided by applicant): The overall goal of this project is to develop and commercialize a simple cell counter for routine enumeration of CD4 cells for management of HIV-infected individuals. HIV-1 mediated CD4 cell destruction is the central immunologic feature of HIV-1 infection. Thus, the CD4 count is a critical measurement in initial disease staging, in monitoring antiretroviral therapy and in managing primary and secondary prophylaxis for opportunistic infections. Flow cytometry is the current standard-of-care for CD4 cell counting. Unfortunately, flow is a central lab-based technique, and sample cold chain and transport, equipment, and operational costs render the technique cost-prohibitive in limited resource settings where HIV prevalence is highest. A simple, point-of-care (POC) CD4 counting tool will fundamentally change HIV-1 management. The first phases of this project have yielded a low-cost prototype instrument that delivers fast, accurate, and reliable CD4 counts for whole blood specimens from both HIV-infected individuals and healthy donors. Building on this success, we propose to complete the technical development by minimizing required user interactions with the device, driving toward an FDA CLIA-waived system. The specific aims are: 1. Simplify the sample processing protocol and design and build a cartridge/instrument prototype for which the only user interaction is whole blood addition. We will investigate and develop assay reagent combinations (e.g., stain, lysis buffer, etc.), reagent packaging, and modified disposable cartridge and instrument designs to reduce the number of liquid transfer steps in the assay. The development goal is a CLIA-waived (or equivalent) system. 2. Incorporate in-cartridge quality controls that confirm correct function and user operation. We will develop a combination of calibration kit components and on-cartridge quality control features, including count calibrators, fluorescent stain indicators and image quality software flags. 3. Demonstrate the accuracy and usability of the CD4 counting system in clinical settings. Field evaluations of the prototype system will be performed at HIV-specific clinics affiliated with the University of California, San Diego (UCSD) Medical Center and in Maputo, Mozambique. Supporting this effort we have established strong clinical collaborations with global health thought leaders. Co-investigators Dr. Robert Schooley and Dr. Constance Benson at UCSD provide critical input on device requirements, and facilitate laboratory evaluations. At the conclusion of this project, the utility, value, and unique capabilities of the MBio point of care C4 cell counter will be strongly established, and the final steps in commercialization, i.e., productin instruments, clinical trials, regulatory submission, and marketing will be accelerated.