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

这个小企业创新研究（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志物。侵袭性细胞的变形性长期以来被假设为赋予它们通过紧密的组织屏障迁移并形成转移的能力。最近，这一想法得到了支持的机械测量细胞分离或直接在生物液体标本。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生物标志物，并且用于临床测定这些特性的工具正在迅速开发。Cytovale？的技术以每秒几千个细胞的通量测量细胞的变形性，与普遍存在的流式细胞仪相当，流式细胞仪允许直接在生物流体中立即测量细胞。该技术已被证明具有实用性：在细胞异质性临床胸腔积液中高度灵敏地检测恶性肿瘤。在这个项目中，它与荧光的整合将提供一种变革性的研究和临床工具，与通过自动化、早期疾病检测和使用定量的新型生物标志物来改善患者护理和降低成本的关键目标保持一致。该项目的更广泛的影响/商业潜力是通过欣赏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）细胞术的整合，该技术已证明其实用性作为一个敏感的检测恶性肿瘤的临床标本，特别是胸腔积液。然而，细胞力学是侵袭性的有吸引力的生物标志物，并且可能在许多生物流体（包括尿液和细针抽吸物）中发现的整个细胞中保守。拟议的活动将进一步提高技术？诊断的准确性。Cytovale开发的仪器将被放置在临床细胞学实验室中，以补充金标准细胞学方法，对生物液体进行高灵敏度筛选，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物之间联系的一个特别强大的工具，这将大大增加从这种使能技术中受益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.