I-Corps: Improving Acoustophoretic-based Cell Sorting Technologies

这个i-Corps项目的更广泛的影响/商业潜力包括改进癌症诊断、更准确的个性化治疗以及减少与癌症相关的公共卫生负担。该项目旨在利用仅在美国估计价值140亿美元的液体活检市场，将基于声学的细胞分选技术商业化，并提供诊断和治疗设备。在乳腺癌、前列腺癌、肺癌和结肠癌等多种肿瘤中，循环肿瘤细胞(CTCs)已被确定为重要的预后生物标志物。然而，从癌症患者的外周血中捕获高纯度的活性CTCs仍然是一个重大的技术挑战。与其他技术相比，基于声学的技术最有前途，因为它在使用无标记和无接触分选保持生物细胞的完整性、功能和活性方面具有固有的优势。声学CTC隔离设备一旦商业化，可以被癌症研究人员用于研究癌症转移和发现新药，可以被医生用于癌症诊断和预后评估，还可以用于开发个性化免疫疗法，以提高治愈率。例如，对分选和扩展的患者特异性CTC进行下游分析可能会显著提高最新突破性免疫治疗方法的应答率。这个I-Corps项目旨在基于研究中开发的最新微流控技术开发商业上可行的声学细胞分选设备。术语“微流体”是指通过利用微米或亚微米尺寸的微型结构，对亚微升或更小体积的流体样品进行微型化处理。利用成熟的微制造技术在微流控平台上实现传统实验室工艺的小型化引起了人们的极大关注，并导致了所谓的芯片上实验室设备的发展。芯片实验室致力于生化过程的集成化、小型化、并行化和自动化，这些过程被执行到一个几平方毫米到几平方厘米大小的小芯片中。更高的自动化程度和更低的能源消耗使这种微流控设备成为护理点(PoC)诊断的极佳候选设备。该团队制造并测试了一种使用表面声波的新型微流控平台，可以有效地从癌症患者的外周血液样本中过滤出循环中的肿瘤细胞(CTCs)。这是一种通用的捕获方案，因为CTC被认为是通用的生物标志物，即大多数类型的癌症在血液或淋巴系统中释放CTC。这种基于声学的细胞分选平台是一种很有前途的方法，可以无标记、无接触地捕获CTCs，保留其固有的生物学特性。

The broader impact/commercial potential of this I-Corps project includes improved cancer diagnostics, more accurate personalized treatments, and reduced public health burden related to cancer. The project is aimed at commercializing acoustic-based cell sorting technologies and providing diagnostic and therapeutic devices, taking advantage of the estimated US $14 billion liquid biopsy market in the United States alone. Circulating tumor cells (CTCs) have already been established as important prognostic biomarkers in many tumor entities namely breast, prostate, lung and colon cancer. However, capture of viable CTCs at high purity from the peripheral blood of cancer patients still poses a significant technical challenge. The acoustic-based techniques are mostly promising, compared to other technologies, due to the inherent advantages in preserving the integrity, functionality, and viability of biological cells using label-free and contact-free sorting. The acoustic CTC isolation devices, once commercialized, can be used by cancer researchers to study cancer metastasis and discover new drugs, can be used by medical doctors for cancer diagnostics and prognosis evaluation, and can be used to develop personalized immunotherapies to increase the cure rate. As an example, the downstream analyses of the sorted and expanded patient-specific CTCs may significantly increase the response rate of the latest groundbreaking immunotherapeutic approaches.This I-Corps project aims to develop commercially viable acoustic cell sorting devices based on the latest microfluidics technologies developed in research. The term 'microfluidics' relates to miniaturized handling of fluidic samples of sub-microliter or lower volume by utilizing miniaturized structures ranging in micron or submicron dimensions. Miniaturization of conventional laboratory processes in microfluidic platforms using well-established microfabrication technology has drawn great attention, and led to the development of the so-called Lab-on-a-Chip devices. Lab-on-a-Chip aims at integration, miniaturization, parallelization, and automation of biochemical processes, performed into a small chip of a few square millimeters to a few square centimeters in size. The higher degree of automation and the reduced energy consumption renders such microfluidic devices excellent candidates for point of care (PoC) diagnostics. This team fabricated and tested a novel microfluidic platform using surface acoustic waves that can effectively filter out circulating tumor cells (CTCs) from peripheral blood samples of cancer patients. This is a generic capture scheme since CTCs are considered to be general biomarkers i.e., most cancer types shed CTCs in the bloodstream or the lymphatic system. This acoustic-based cell sorting platform is a promising method for capturing CTCs label-free and contact-free, preserving their inherent biological characteristics.