SBIR Phase I: Hybrid Deformability and Fluorescence Cytometer for Biomarker Development and Validation

这个小型企业创新研究(SBIR)第一阶段项目将解决整合两个强大的单细胞分析工具的挑战，目的是开发和验证新的恶性肿瘤生物标记物。长期以来，侵袭性细胞的变形性一直被认为是为了赋予它们通过严密的组织屏障迁移并形成转移的能力。最近，从生物体液样本中分离或直接从生物体液样本中分离的细胞的机械测量支持了这一想法。这种来自生物科学和物理科学的思想的融合代表了一种机械的生物标记物，临床上用于分析这些特性的工具正在迅速开发。Cytovale-S技术以每秒数千个细胞的吞吐量测量细胞变形性，可与无处不在的流式细胞仪相媲美，后者可以直接在生物液中立即测量细胞。这项技术有一个已被证明的实用价值：高度敏感地检测细胞异质性临床胸腔积液中的恶性肿瘤。它与荧光技术在这个项目中的集成将提供一个变革性的研究和临床工具，与通过自动化、疾病早期检测和使用定量的新型生物标记物来改善患者护理和降低成本的关键目标很好地保持一致。该项目的更广泛的影响/商业潜力是通过评估该技术在研究和临床环境中的适用性来实现的。即使没有与荧光(流式)细胞术相结合，这项技术也证明了它在临床标本中作为恶性肿瘤的灵敏检测器的有效性，特别是胸腔积液。然而，细胞力学是一个有吸引力的侵袭性生物标志物，在许多生物液中发现的细胞中可能都是保守的，包括尿液和细针抽吸物。拟开展的活动将进一步提升S的技术诊断准确率。Cytovale开发的仪器将被放置在临床细胞学实验室，作为黄金标准细胞学方法的补充，对生物液进行高灵敏度筛选，并消除不必要的、侵入性的和昂贵的后续程序。混合仪器也将是探索细胞力学和传统标记之间联系的特别强大的工具，这将极大地扩大将受益于这一使能技术的研究实验室的数量。

This Small Business Innovation Research (SBIR) Phase I project will address the challenge of integrating two powerful single-cell analysis tools with the aim of developing and validating new biomarkers for malignancy. The deformability of invasive cells has long been hypothesized to confer their ability to migrate through tight tissue barriers and form metastases. Recently, this idea has been supported by mechanical measurements of cells either isolated from or directly in biological fluid specimens. This convergence of ideas from both biological and physical sciences represents a mechanical biomarker, and tools to be employed clinically to assay these properties are rapidly being developed. Cytovale?s technology measures cell deformability at a throughput of several thousand cells per second, comparable to the ubiquitous flow cytometer, which allows immediate measurement of cells directly in biological fluids. This technology has a demonstrated utility: highly sensitive detection of malignancy in cellularly heterogeneous clinical pleural effusions. Its integration with fluorescence in this project will provide a transformational research and clinical tool, well-aligned with the critical aims of improving patient care and reducing costs through automation, early detection of disease, and use of quantitative, novel biomarkers.The broader impact/commercial potential of this project is realized by appreciating the applicability of the technology across research and clinical settings. Even without integration with fluorescence (flow) cytometry the technology has demonstrated its utility as a sensitive detector of malignancy in clinical specimens, specifically, pleural effusions. However, cell mechanics is an attractive biomarker for invasiveness, and is likely conserved throughout cells found in many biological fluids, including urine and fine needle aspirates. The proposed activity will further enhance the technology?s diagnostic accuracy. The instruments developed by Cytovale will be placed in clinical cytology labs to complement gold standard cytological methods, performing high sensitivity screens of biological fluids and eliminating unnecessary, invasive, and costly follow-up procedures. The hybrid instrument will also be an especially powerful tool for exploring connections between cell mechanics and traditional markers, which greatly extends the number of research laboratories which would benefit from this enabling technology.