Automated molecular diagnosis on fine needle aspirates (FNA)

细针抽吸 (FNA) 的自动分子诊断

• 批准号: 10323396
• 负责人: Laura E Kelley
• 金额: $ 40万
• 依托单位: AIKILI BIOSYSTEMS INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323396
• 关键词: ACVRL1 gene; Address; Algorithms; Antibodies; Architecture; Biological Assay; Biological Markers; Biopsy; CD19 gene; CD3 Antigens; CD8B1 gene; Cell Cycle; Cell Line; Cell Size; Cell Survival; Cells; Chemicals; Classification; Clinical; Consent; Core Biopsy; Coupled; Custom; Cyclin D1; Cyclooctenes; Cytology; Cytometry; Cytopathology; Data Analyses; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; ERBB2 gene; Eligibility Determination; Epidermal Growth Factor Receptor; Epithelial; Fine needle aspiration biopsy; Flow Cytometry; Fluorochrome; Foundations; Goals; Gold; Guns; Harvest; Head and neck structure; Hour; Hydrogen Peroxide; Image; Image Cytometry; Immunohistochemistry; Institutional Review Boards; Intervention; Lesion; Light; Lymphoid Tissue; Lymphoma; Lymphoma cell; MS4A1 gene; Malignant Neoplasms; Methods; Molecular Analysis; Molecular Diagnosis; Molecular Profiling; Morbidity - disease rate; Mucin 1 protein; PTPRC gene; Palpable; Pathology; Patients; Performance; Phase; Play; Procedures; Process; Reagent; Role; Sampling; Sensitivity and Specificity; Specimen; Speed; Staging; Stains; Stress Tests; System; TNFRSF8 gene; Technology; Thyroid Nodule; Time; Tissues; Treatment Efficacy; Validation; Visualization; cancer biomarkers; cancer care; cancer cell; cancer clinical trial; cancer type; clinical application; cost; diagnostic platform; drug development; experimental study; fluorophore; image guided; improved; interest; lymph nodes; minimally invasive; molecular diagnostics; multidimensional data; novel; novel diagnostics; pharmacodynamic biomarker; pre-clinical; protein biomarkers; protein profiling; research clinical testing; scale up; standard of care; success

Molecular analyses of cancer cells are essential in establishing diagnoses and guiding available treatments. Conventional tissue biopsies, while providing key information on tissue architecture, are associated with morbidity and high cost and therefore are not performed as frequently as would be clinically desirable. An alternative to cutting core biopsy guns are fine needle aspirations (FNAs), which can be performed with minimal intervention and allow for less invasive and/or repeated sampling from small lesions. However, workup of FNA specimens remains challenging using conventional cytology and immunohistochemistry. To address these barriers, Aikili Biosystems seeks to enable same-day diagnostic workup of FNA samples using a proprietary “FAST” assay and automated image cytometer. A key component of Aikili's technology is our proprietary cell cycling method (FAST), which builds upon and expands previous assay capabilities (4- channel multiplexing) to over 20-40 biomarkers; it is coupled with our image cytometer, a stand-alone diagnostic platform capable of automated cancer cell classification in <2 hours. Building upon initial development and pre-clinical validation, in Aim 1, we will validate FAST antibody probes in >15 cancer markers, integrate sample processing with Aikili's cytometry system and analyze associated images using the device. In Aim 2, we will evaluate the benefit of the integrated technology for rapid, same-day analysis of clinical samples, specifically lymphoma FNA samples (n = 40) stained with FAST-linker modified antibody probes. Phase I will be deemed successful when Aikili's system reliably detects and classifies lymphoma cells compared to gold standards. Successful completion of Phase I will lay the foundation for a Phase II application for clinical testing and manufacture of cytometry systems and commercial cartridges for multiple cancers. This platform has potential to transform cellular diagnostics and pathology workflows through rapid, same-day analyses of minimally invasive FNAs; its robust analyses of pharmacodynamic markers has potential to enable development of new, clinically meaningful biomarkers that can be used to advance drug development.

癌细胞的分子分析对于建立诊断和指导可用的 治疗。传统的组织活检，同时提供关键信息的组织结构， 具有发病率和高成本，因此不能像临床上所希望的那样频繁地进行。一个 切割芯活检枪的替代方案是细针抽吸（FNA），可以使用 最小的干预，并允许较小的侵入性和/或从小病变重复采样。然而，在这方面， 使用常规细胞学和免疫组织化学对FNA标本进行后处理仍然具有挑战性。到 为了解决这些障碍，Aikili Biosystems寻求实现FNA样本的当天诊断检查 使用专有的“FAST”分析和自动图像细胞仪。Aikili技术的关键组成部分 是我们专有的细胞循环方法（FAST），它建立在并扩展了以前的分析能力（4- 通道多路复用）超过20-40个生物标志物;它与我们的图像细胞仪，一个独立的 诊断平台能够在2小时内自动进行癌细胞分类。建立在最初的 在目标1中，我们将在>15种癌症中验证FAST抗体探针， 标记，将样品处理与Aikili的细胞仪系统集成，并使用 设备.在目标2中，我们将评估集成技术在快速、当天分析 临床样品，特别是淋巴瘤FNA样品（n = 40），用FAST-接头修饰的抗体染色 probes.当Aikili的系统可靠地检测和分类淋巴瘤时，I期将被视为成功 与黄金标准相比。第一阶段的成功完成将为第二阶段奠定基础。 应用于临床测试和制造细胞计数系统和商业盒， 多种癌症该平台有可能改变细胞诊断和病理学工作流程 通过对微创FNA的快速，当天分析;其强大的药效学分析， 标志物具有开发新的、临床上有意义的生物标志物的潜力， 推进药物开发。