Clinical Cytophone platform for detection of circulating melanoma cells.

用于检测循环黑色素瘤细胞的临床 Cytophone 平台。

• 批准号: 10246167
• 负责人: Issam Makhoul
• 金额: $ 9.68万
• 依托单位: CYTOASTRA, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246167
• 关键词: Acoustics; Adult; Aftercare; Agreement; Algorithms; Arkansas; Biological Assay; Blood; Blood Volume; Blood specimen; Cancer Center; Cell Count; Cellular Assay; Cessation of life; Clinic; Clinical; Clinical Data; Clinical Trials; Code; Collection; Color; Contrast Media; Data; Data Analyses; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Early Diagnosis; Epidemic; Flow Cytometry; Generations; Goals; Hour; In Vitro; Individual; Institutes; L Cells; Label; Laboratories; Lasers; Light; Malignant Neoplasms; Mammography; Mass Screening; Medical; Melanins; Melanoma Cell; Methods; Monitor; Motion; Multi-Institutional Clinical Trial; Neoplasm Circulating Cells; Neoplasm Metastasis; Operating Rooms; Organ; Patients; Performance; Phase; Physiologic pulse; Primary Neoplasm; Prognosis; Progress Reports; Public Health; Pulse Rates; Reaction Time; Reproducibility; Residual Tumors; Resolution; Science; Screening procedure; Signal Transduction; Skin; Skin Pigmentation; Small Business Technology Transfer Research; Staging; Survival Rate; System; Technology; Temperature; Testing; Time; Transducers; Ultrasonic Transducer; Universities; Veins; Whole Blood; base; clinically relevant; cohort; commercialization; design; detection assay; detection limit; detection platform; diagnostic platform; disease diagnosis; improved; in vivo; innovation; irradiation; lens; malignant breast neoplasm; melanoma; mortality; novel; novel strategies; pilot trial; portability; prevent; prototype; signal processing; skin color; skin photodamage; tumor; wearable device

Most patients with melanoma die from metastatic disease as the result of circulating tumor cells (CTCs) spreading from a primary tumor through the blood to vital organs. Despite significant progress in the development of in vitro CTC-detection assays, they still have low sensitivity due to the small samples of blood taken. To overcome these problems, we developed in vivo photoacoustic (PA) flow cytometry (PAFC) and demonstrated its feasibility in pilot trials with melanoma patients where we used melanin in CTCs as an intrinsic PA contrast agent. These trials identified the key limitations of the PAFC platform, such as a stationary laboratory setup with a large expensive laser, a motion- and skin-pigmentation-sensitive recording system, no spectral identification of melanoma CTCs in the blood background, a detection limit 20–30-fold lower than the ultimate threshold, and limited clinical data. These obstacles prevent the routine use of this promising technology. The goal of our Phase I STTR proposal is to demonstrate the feasibility and clinical relevance of an advanced PAFC-based “Cytophone” prototype for early, fast (from 20 sec to a few min), noninvasive (no blood draw), label-free (no exogenous contrast agents), and safe (no skin photodamage or blood contamination concern) detection of CTCs in melanoma patients. To achieve this goal, we will optimize the Cytophone’s parameters and eventually explore its clinical capabilities during testing of melanoma patients. We expect to obtain statistically significant data that will demonstrate an unprecedented 1000-fold increase in sensitivity, allowing us to detect 1 CTC in 1 liter of blood with our robust, wearable, and portable Cytophone device. This level of sensitivity will allow us to detect CTCs released from small tumors (e.g., ≤ 1 mm), which are often not identified with current diagnostic techniques. The goal of our Phase II STTR proposal is to develop commercial Cytophone prototypes to be tested in multicenter clinical trials. We expect that the Cytophone can eventually be used in melanoma-focused clinics throughout the world for early diagnosis, monitoring treatment efficiency, and as a mass melanoma screening tool (as the mammogram is used for breast cancer).

大多数黑色素瘤患者死于循环肿瘤细胞 (CTC) 导致的转移性疾病 尽管在治疗方面取得了重大进展，但从原发性肿瘤通过血液扩散到重要器官。 体外 CTC 检测方法的发展，由于血液样本较少，其灵敏度仍然较低 为了克服这些问题，我们开发了体内光声（PA）流式细胞术（PAFC）和 它在黑色素瘤患者中进行的试点试验的可行性证明了我们在 CTC 中使用黑色素作为 这些试验确定了 PAFC 平台的主要局限性，例如固定的。 实验室设置有大型昂贵的激光器、运动和皮肤色素敏感记录系统，没有 血液背景中黑色素瘤 CTC 的光谱鉴定，检测限比传统方法低 20-30 倍 最终阈值和有限的临床数据阻碍了这种有希望的常规使用。 我们第一阶段 STTR 提案的目标是证明该技术的可行性和临床相关性。 一种先进的基于 PAFC 的“Cytophone”原型，用于早期、快速（从 20 秒到几分钟）、非侵入性（无创） 抽血）、无标签（无外源性造影剂）、安全（无皮肤光损伤或血液 污染问题）黑色素瘤患者中 CTC 的检测 为了实现这一目标，我们将优化 Cytophone 的参数，并最终在黑色素瘤患者测试过程中探索其临床功能。 我们期望获得统计上显着的数据，这将证明前所未有的 1000 倍增长 灵敏度，使我们能够使用坚固、可穿戴、便携式 Cytophone 检测 1 升血液中的 1 个 CTC 这种水平的灵敏度将使我们能够检测小肿瘤（例如 ≤ 1 毫米）释放的 CTC。 目前的诊断技术通常无法识别。我们第二阶段 STTR 提案的目标是 开发商业 Cytophone 原型并在多中心临床试验中进行测试。 Cytophone 最终可以用于世界各地以黑色素瘤为重点的诊所进行早期诊断， 治疗监测效率，并作为大规模黑色素瘤筛查工具（因为乳房X光检查用于 乳腺癌）。