A Rapid Multiplexed Test for the Screening of Sepsis and Organ Dysfunction at the Point of Care

摘要 InstaDiagnostics(IDI)正在开发一个护理点(POC)诊断技术平台，目标是 在初级保健中心、社区为患者提供早期检测、筛查和治疗监控 诊所、紧急护理中心和急诊科。该设备由便携式阅读器( InstaReader)和一次性墨盒(InstaCartridge)。一系列疾病专用墨盒将允许 在一台设备上可以检测到多种疾病。该系统提供临床实验室质量的能力 不到15分钟的结果将使医务人员能够立即诊断患者，以及 允许患者避免额外的抽血行程、漫长的结果等待时间或延迟 诊断和跟踪测试。IDI的诊断平台将提高患者的护理/满意度，医疗 结果和医疗服务提供者的工作流程，同时降低总体医疗成本。 脓毒症被定义为由于宿主对感染的反应失调而导致的危及生命的器官功能障碍。 器官功能障碍与败血症密切相关，仅影响一个器官的情况很少见 受影响的器官数量越多，死亡风险就越高。在全球范围内，败血症是最可预防的 死亡和残疾原因，每年确诊3000多万例，死亡600万例。在美国 疾控中心估计，每年约有170万例病例和27万人死亡。的确有 强有力的证据表明，如果及早诊断，败血症在很大程度上是可以预防的，器官功能障碍是可逆的。血样 感染、炎症和器官功能障碍的检测有助于脓毒症的筛查和早期诊断， 特别是在初级保健设施中。然而，这些测试大多是在中央实验室进行的， 考虑到严重的脓毒症和器官衰竭的进展，可能需要几个小时甚至几天的时间才能得到结果。 因此，一种改进的多重试验，用于筛查脓毒症和器官功能障碍的高危个体 在POC立即进行，对于改善这些患者的预后至关重要。 我们的总体目标是开发一种对降钙素原(PCT)、C反应蛋白(CRP)、 乳酸、肌酐、胆红素、尿素氮、纤维蛋白原和D-二聚体。第一阶段的重点是： 目的1：建立和鉴定PCT、CRP、乳酸和肌酐的测定方法 目标2：开发多技术面包板阅读器和多路复用盒，以同时 测定同一样本中的PCT、CRP、乳酸和肌酐水平 第二阶段将集中于扩大小组，并进行试点临床研究，以证明 测试的性能和实用性。然后，将为进一步的患者提供器官特异性面板 评估。

Abstract Instadiagnostics (IDI) is developing a point-of-care (POC) diagnostic technology platform with the goal of providing early detection, screening, and treatment monitoring for patients at primary care centers, community clinics, urgent care centers, and emergency departments. The device consists of a portable reader (the InstaReader) and disposable cartridges (InstaCartridge). A range of disease specific cartridges will allow for multiple diseases be detected on a single device. The system's ability to provide clinical laboratory quality results in less than 15 minutes will give medical workers the capability to immediately diagnose patients, and allows patients to avoid additional trips to have blood drawn, lengthy wait times for results, or delays in diagnosis and follow up testing. IDI's diagnostic platform will improve patient care/satisfaction, medical outcomes, and workflow for healthcare providers, while reducing overall medical costs. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is closely associated with sepsis and it is rare that just a single organ is impacted, the higher number of organs impacted the higher is the risk for mortality. Globally sepsis is the most preventable cause of death and disability, with over 30 million cases diagnosed annually and 6 million deaths. In the U.S. the CDC estimates that there are approximately 1.7 million cases and 270,000 deaths annually. There is strong evidence that if diagnosed early, sepsis is largely preventable and organ dysfunction is reversible. Blood tests for infection, inflammation, and organ dysfunction can aid in the screening and early diagnosis of sepsis, especially in primary care facilities. However, most of these tests are performed in centralized laboratories and it can take hours or even days to get the results allowing for the progression to severe sepsis and organ failure. Therefore, an improved, multiplexed test, for screening high-risk individuals for sepsis and organ dysfunction performed immediately at the POC, is essential to improve prognosis for these individuals. Our overall Sepsis goal is to develop a multiplexed test for Procalcitonin (PCT), C-Reactive Protein (CRP), Lactate, Creatinine, Bilirubin, Blood Urea Nitrogen, Fibrinogen, and D-Dime. This Phase I will be focused on: Aim 1: Develop and characterize assays for PCT, CRP, Lactate and Creatinine Aim 2: Development of a multi-technology bread-board reader and multiplexed cartridge to simultaneously measure levels of PCT, CRP, Lactate, and Creatinine in the same sample Phase II will focus on expanding on the panel, and conducting a pilot clinical study to demonstrate the performance and utility of the test. It will then be followed with organ specific panels for further patient evaluation.