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

使用 PointCheck 降低接受化疗的癌症患者发热性中性粒细胞减少症的发生率：便携式非侵入性中性粒细胞减少症分析仪

• 批准号: 10159219
• 负责人: Carlos Castro-Gonzalez
• 金额: $ 80.6万
• 依托单位: LEUKO LABS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-12 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159219
• 关键词: Accident and Emergency department; Algorithms; Anti-Infective Agents; Biological Assay; Blood; Blood capillaries; Blood specimen; Cancer Patient; Caring; Cells; Chemotherapy-Oncologic Procedure; Classification; Clinic; Clinical; Clinical Research; Colony-Stimulating Factors; Computer software; Data; Detection; Development; Devices; Early Diagnosis; Early treatment; Evaluation; Feedback; Fever; Fingers; Goals; Gold; Growth; Healthcare; Home; Hospitalization; Hospitals; Image Analysis; Imaging Device; Immunosuppression; Incidence; Infection; Infection prevention; Intervention; Interview; Leukocytes; Life; Malignant Neoplasms; Manuals; Measurement; Medical; Microcirculation; Monitor; Morbidity - disease rate; Nail Fold; Neutropenia; Notification; Oncology; Optics; Outpatients; Participant; Pathway interactions; Patients; Performance; Phase; Physicians; Pilot Projects; Process; Production; Protocols documentation; Quality Control; Reagent; Reproducibility; Risk; Safety; Sampling; Self Administration; Sensitivity and Specificity; Serious Adverse Event; Small Business Innovation Research Grant; Structure of nail of finger; System; Technology; Testing; Time; Treatment Side Effects; Triage; Video Microscopy; Visit; automated analysis; base; chemotherapy; clinical diagnostics; cohort; commercialization; cost; data acquisition; data exchange; data quality; design; experience; fighting; hospital readmission; improved; improved outcome; meetings; miniaturize; mortality; mortality risk; neutrophil; non-invasive optical imaging; optical imaging; point of care; portability; prevent; prototype; research clinical testing; software systems; success; usability; validation studies

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.

项目摘要 第二阶段SBIR项目的目标是优化和验证PointCheck，这是第一个非侵入性的 床旁（POC）设备，用于识别接受癌症化疗的患者， 阶段性发热性中性粒细胞减少症，需要立即治疗以防止严重感染。每年在 在美国，有65万癌症患者接受化疗。治疗的一个副作用是中性粒细胞减少，这是一个生命- 由低水平中性粒细胞引起的威胁性疾病，导致住院治疗， 死亡率和相关总成本每年为27亿美元。PointCheck使用非侵入性光学成像， 甲襞毛细血管微循环检测严重的中性粒细胞减少症，而不需要血液样本。是 预期用于接受化疗的癌症患者，以识别中性粒细胞减少症患者 需要及时治疗以避免严重感染、再入院费用和发病率。因为它 是独立的，不需要血液采样或试剂，它最终可由患者在 在家监测化疗期间的血细胞计数 在该项目的第一阶段，Leuko Labs成功地：（1）从原始材料中自动选择合适的毛细管， （2）自动检测指示中性粒细胞在甲襞毛细血管中通过的流动间隙; (3)自动分析手动收集的44例癌症化疗患者甲襞毛细血管的1分钟视频 患者，并确定了那些具有IV级中性粒细胞减少症（<500中性粒细胞/mm 3）的患者，其分类良好 性能（AUC=0.95）。 该项目第二阶段的目标是通过设计，完成将PointCheck推向市场的后续步骤， 生产就绪的PointCheck器械，并在临床研究中对其进行验证，以支持II类器械的备案 Novo获得FDA批准。目标1是设计一个可生产的PointCheck硬件原型， 患者可以通过对光学部件进行消毒而不受监督地使用。目标2是开发和整合 图像分析软件流水线到生产就绪单元。目标3是完成初步试点可用性研究 在3个队列的30例患者（共n=90）中进行，因为器械在目标1和2中进行了优化;本研究将 还确认PointCheck已准备好进行目标4中的关键临床研究。目标4是完成一个关键的 在临床诊断研究中验证PointCheck的临床研究（n=100），以确认IV级中性粒细胞减少症 可以安全有效地识别。目标5是向FDA提交II类De Novo批准包。 第二阶段项目的成功完成将满足最低可行产品的要求， 使这种首创技术能够初步商业化，以改善发热的管理， 中性粒细胞减少症的癌症患者进行化疗。

项目成果

Usability Evaluation of a Noninvasive Neutropenia Screening Device (PointCheck) for Patients Undergoing Cancer Chemotherapy: Mixed Methods Observational Study.

• DOI: 10.2196/37368
• 发表时间: 2022-08-09
• 期刊: JOURNAL OF MEDICAL INTERNET RESEARCH
• 影响因子: 7.4
• 作者: Lamaj, Ganimete;Pablo-Trinidad, Alberto;Butterworth, Ian;Bell, Nolan;Benasutti, Ryan;Bourquard, Aurelien;Sanchez-Ferro, Alvaro;Castro-Gonzalez, Carlos;Jimenez-Ubieto, Ana;Baumann, Tycho;Rodriguez-Izquierdo, Antonia;Pottier, Elizabeth;Shelton, Anthony;Martinez-Lopez, Joaquin;Sloan, John Mark
• 通讯作者: Sloan, John Mark

Visualization of blood cell contrast in nailfold capillaries with high-speed reverse lens mobile phone microscopy.

使用高速反向镜头手机显微镜观察甲襞毛细血管中的血细胞对比度。

• DOI: 10.1364/boe.382376
• 发表时间: 2020
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: McKay,GregoryN;Mohan,Nela;Butterworth,Ian;Bourquard,Aurélien;Sánchez-Ferro,Álvaro;Castro-González,Carlos;Durr,NicholasJ
• 通讯作者: Durr,NicholasJ