A Culture-Free Platform for Rapid Pathogen Identification

描述（由申请人提供）：真菌败血症或真菌血症是一种严重的公共卫生问题，在美国每年困扰超过100，000名患者，其中近38%的患者无法存活。在真菌血症中，早期靶向治疗可以挽救生命，考虑到疾病发展的速度，这可能是改善预后的最关键因素。不幸的是，鉴于当今耗时的诊断过程，这种疾病的根本原因通常被发现得太晚了。目前的诊断不便于早期启动靶向抗真菌干预-因为它们需要培养，这需要长达2-5天的时间来准确识别感染病原体。因此，目前的治疗方案使用“最佳猜测”的方法，这不仅是不太有效，但同样增加并发症，并增加耐药病原体的流行。在满足并超越了我们的第一阶段特定目标后，该第二阶段提案侧重于将整个诊断自动化为完全集成的样品到答案消耗品，从而能够在大约2小时内直接从放血标本中自动识别临床上最流行的真菌病原体;而无需人为干预。我们将开发的样本到答案的诊断将产生深远的影响，通过提供一种开发假设驱动的一线干预的手段来改善结果，以及减少过度和不必要的抗菌药物的使用。为了在第二阶段取得成功，我们在HelixBind组建了一支一流的团队，包括检测开发、合成核酸类似物应用、样品到答案自动诊断的设计和实施以及生物医学仪器开发方面的专家。此外，我们还招募了临床微生物学、表面化学和核酸类似物方面的关键战略顾问，以及在医疗器械开发和商业化方面具有经验的成功企业家。我们将共同建立在我们已经令人印象深刻的第一阶段结果的基础上，建立了直接从加标人体样本中检测低于10 CFU/ml灵敏度水平的种属水平能力。为了建立我们的自动化和无培养诊断的性能能力，我们将在我们的临床合作伙伴的帮助下，通过评估我们诊断的临床特异性和灵敏度来完成第二阶段。在实现了我们的II期特定目标后，我们将继续前进，开发可部署的仪器/耗材，并验证我们的整个诊断，为关键临床试验做准备。

DESCRIPTION (provided by applicant): Fungal sepsis, or fungemia, is a serious public health concern afflicting over 100,000 patients every year in the US where almost 38% of those do not survive. In fungemia early targeted treatment is life-saving, and considering the rate at which the disease develops, is perhaps the most crucial factor to improving outcomes. Unfortunately, given the time-consuming diagnostic process today, the underlying cause of this disease is typically identified too late. Current diagnostics do not facilitate early initiation of a targeted antifungal intervention - as they require culturing, which requires as long as 2-5 days for accurate identification of the infecting pathogen. Hence current treatment protocols use 'best-guess' approaches which are not only less effective, but likewise increase complications, and increase the prevalence of drug resistant pathogens. Having met our and exceeded our Phase I Specific Aims, this Phase II proposal focuses on the automation of the entire diagnostic into a fully-integrated, sample-to-answer consumable enabling the automated species- level identification of the most clinically prevalent fungal pathogens directly from phlebotomy specimens, in roughly 2 hours; without human intervention. The sample-to-answer diagnostic we will develop will have profound impact, both by improving outcomes by providing a means to develop a hypothesis driven first-line intervention, and likewise by reducing the use of excessive and unnecessary antimicrobials. To succeed in this Phase II we have put together a top-notch team at HelixBind, including experts in assay development, application of synthetic nucleic acid analogues, the design and implementation of sample-to- answer automated diagnostics, and in biomedical instrumentation development. Additionally we have enlisted key strategic advisors in clinical microbiology, surface chemistry, and nucleic acid analogues as well as successful entrepreneurs with experience in the development and commercialization of medical devices. Together, we will build upon our already impressive Phase I results, having established species level capability at sub-10 CFU/ml sensitivity levels directly from spiked human samples. To establish the performance capability our automated and culture-free diagnostic, we will culminate this Phase II by assessing the clinical specificity and sensitivity of our diagnostic wit the assistance of our clinical partner. Having achieved our Phase II Specific Aims, we will move forward and develop deployable instrumentation/consumables and validate our entire diagnostic in preparation for the pivotal clinical trial.