SBIR Phase I: Magnetic Sifter for Rapid Isolation of Rare Cells

这个小型企业创新研究(SBIR)第一阶段项目将开发一种用于检测和分析循环肿瘤细胞(CTCs)的改进设备。CTCs是了解转移过程的窗口，是早期发现和治疗转移性癌症的关键。CTCs的检测、量化和表征具有改变肿瘤学的潜力，但在常规条件下分离它们仍然存在问题。正在开发的CTC样品制备技术是快速的，通过对捕获的细胞进行基因分型或表型分析，可能具有很高的信息量，而且成本低。它将使影响患者护理的新一代肿瘤诊断成为可能。在这个第一阶段的项目中，目标是建立一个原型设备，然后评估它从全血中捕获和回收少量癌细胞的能力。初步数据证明了该方法的可行性。这项研究的结果将评估捕获和回收CTCs的替代方法，目标是在需要60分钟或更短的过程中恢复90%的细胞。该项目更广泛的影响/商业潜力将是一种回收稀有细胞的设备，然后可以分析这些细胞的信息突变和染色体重排，从而为患者的治疗提供信息。第一代CTC测试只提供细胞计数。虽然CTC计数的预后价值被接受，但许多临床医生对这些相对昂贵的测试的价值持怀疑态度。这个项目的目标是第二代CTC测试，它不仅有助于细胞计数，而且还可以恢复捕获的细胞用于分析。通过简单的抽血，就可以对癌症患者的肿瘤进行基因分型，并据此量身定做治疗方案。我们描述了一个多功能的平台，除了CTCS之外，还有许多研究和临床应用。这些应用包括使用母体血液中的胎儿细胞进行非侵入性产前诊断，以及用于再生医学的干细胞分离。基于相同分离原理的设备可以用于分离干细胞，以便移植到梗塞心肌、骨不连骨折和许多其他组织中。这种细胞分离设备将通过简化细胞分离过程，使干细胞研究转化为临床应用。

This Small Business Innovation Research (SBIR) Phase I project will develop an improved device for the detection and analysis of circulating tumor cells (CTCs). CTCs provide a window into the metastatic process, and are key to early detection and treatment of metastatic cancer. Detection, quantification, and characterization of CTCs has the potential to transform oncology, yet their isolation under routine conditions remains problematic. The CTC sample preparation technology under development is rapid, potentially highly informative through genotyping or phenotypic analysis of captured cells, and low cost. It will enable a new generation of oncodiagnostics that impact patient care. During this Phase I project, the goal is to build a prototype device, then evaluate its ability to capture and recover small numbers of cancer cells from whole blood. The preliminary data demonstrates the feasibility of this approach. The results of this study will evaluate alternative means of capturing and recovering CTCs, with the goal of 90% recovery of cells in a procedure requiring 60 minutes or less. The broader impact/commercial potential of this project will be a device to recover rare cells that can then be analyzed for informative mutations and chromosomal rearrangements that can inform patient therapy. First generation CTC tests provide only cell counts. While the prognostic value of CTC counts is accepted, many clinicians view the value of these relatively expensive tests with skepticism. The goal of this project is a second generation CTC test that facilitates cell counts, but also recovers captured cells for analysis. Through a simple blood draw, a cancer patient's tumor can be genotyped, and therapy can be tailored accordingly. We describe a versatile platform with many research and clinical applications beyond CTCs. These applications include noninvasive prenatal diagnostics using fetal cells in maternal blood, and stem cell isolation for regenerative medicine. A device based on the same separation principles could be used to isolate stem cells for implantation in infarcted myocardium, non-union bone fractures, and many other tissues. This cell separation device will enable the translation of stem cell research to clinical application by simplifying the cell isolation process.