Reducing the incidence of febrile neutropenia in cancer patients treated with chemotherapy with PointCheck: a portable non-invasive neutropenia analyzer

项目总结 这个二期SBIR项目的目标是优化和验证PointCheck，第一个非侵入性的 护理点(POC)设备，用于识别接受癌症化疗的患者是否患有早期- 处于发热期的中性粒细胞减少症，需要立即治疗以防止严重感染。每年在世界上 在美国，有65万名癌症患者接受化疗。治疗的一个副作用是中性粒细胞减少，一种生活- 中性粒细胞水平低导致住院的威胁条件，增加 死亡率和每年相关的总成本为27亿美元。PointCheck使用非侵入性光学成像 甲皱毛细血管中的微循环检测严重的中性粒细胞减少，而不需要血样。它是 供接受化疗的癌症患者使用，以识别中性粒细胞减少症患者 他们需要及时治疗，以避免严重感染、再次住院费用和发病率。因为它 是自给自足的，不需要抽血或试剂，患者最终可以在 在化疗期间在家监测血细胞计数。 在这个项目的第一阶段，Leuko实验室成功地：(1)自动从RAW中选择合适的毛细血管 视频；(2)自动检测显示中性粒细胞在甲皱毛细血管中通过的流动间隙；以及 (3)自动分析人工收集的44个癌症化疗的1分钟甲皱毛细血管视频 患者，并确定那些中性粒细胞减少IV级(&lt；500个中性粒细胞/mm~3)的患者，并进行了出色的分类 性能(AUC=0.95)。 此第二阶段项目的目标是完成下一步，通过设计将PointCheck推向市场 一种可投入生产的PointCheck设备，并在临床研究中进行验证，以支持II类药物的提交 Novo获得FDA的批准。目标1是设计一个可用于生产的PointCheck硬件原型 通过将光学部件微型化，患者可以无人监督地使用。目标2是开发和集成 图像分析软件正在流水线中，准备投入生产。目标3是完成初步的试点可用性研究 在AIMS 1和AIMS 2中优化装置时，在30名患者(总共90名)的3个队列中进行；本研究将 还要确认PointCheck已经为目标4中的关键临床研究做好了准备。目标4是完成关键的 临床诊断研究中确认PointCheck的临床研究(n=100)，以确认IV级中性粒细胞减少症 可以安全有效地进行识别。目标5是向FDA提交一份新的II类批准方案。 成功完成该第二阶段项目将满足最低可行产品的要求，并 实现这一首创技术的初步商业化，以改善发烧的管理 接受化疗的癌症患者的中性粒细胞减少。

PROJECT SUMMARY The goal of this Phase II SBIR project is to optimize and validate PointCheck, the first non-invasive point-of-care (POC) device that identifies patients undergoing cancer chemotherapy who have early- stage febrile neutropenia and need immediate treatment to prevent serious infections. Every year in the US, 650,000 cancer patients are treated with chemotherapy. One side effect of treatment is neutropenia, a life- threatening condition caused by low levels of neutrophils that leads to hospitalization, increased risk of mortality and total associated costs of $2.7B annually. PointCheck uses noninvasive optical imaging of microcirculation in nailfold capillaries to detect severe neutropenia without the need for a blood sample. It is intended for use by cancer patients undergoing chemotherapy, in order to identify patients with neutropenia who require prompt treatment to avoid serious infections, hospital readmission costs and morbidity. Because it is self-contained and does not require blood sampling or reagents, it ultimately may be used by patients at home to monitor blood counts between chemotherapy sessions. In Phase I of this project, Leuko Labs successfully: (1) automated the selection of suitable capillaries from raw videos; (2) automated the detection of flow gaps that indicate passage of neutrophils in nail-fold capillaries; and (3) automatically analyzed manually-collected 1-min videos of nailfold capillaries from 44 cancer chemotherapy patients and identified those with grade IV neutropenia (<500 neutrophils/mm3) with an excellent classification performance (AUC=0.95). The objective of this Phase II project is to complete the next steps to bring PointCheck to market by designing a production-ready PointCheck device and validating it in a clinical study to support the filing of a Class II De Novo approval to the FDA. Aim 1 is to design a production-ready PointCheck hardware prototype for unsupervised use by patients by miniaturizing the optical components. Aim 2 is to develop and integrate the image analysis software pipeline to the production-ready unit. Aim 3 is to complete an initial pilot usability study performed in 3 cohorts of 30 patients (n=90 total) as the device is optimized in Aims 1 and 2; this study will also confirm that PointCheck is ready for the pivotal clinical study in Aim 4. Aim 4 is to complete a pivotal clinical study to validate PointCheck in a clinical diagnostic study (n=100) to confirm that grade IV neutropenia can be identified safely and effectively. Aim 5 is to submit a Class II De Novo approval package to the FDA. Successful completion of this Phase II project will fulfill the requirements for a minimum viable product and enable initial commercialization of this first-in-kind technology to improve the management of febrile neutropenia in cancer patients undergoing chemotherapy.