Ansari Ali, Patel Reema, Schultheis Kinsey, Naumovski Vesna, Imoukhuede P I
Department of Bioengineering, University of Illinois at Urbana-Champaign.
Department of Liberal Arts & Sciences, University of Illinois at Urbana-Champaign.
J Vis Exp. 2016 Sep 20(115):54315. doi: 10.3791/54315.
One of the limiting factors to the adoption and advancement of personalized medicine is the inability to develop diagnostic tools to probe individual nuances in expression from patient to patient. Current methodologies that try to separate cells to fill this niche result in disruption of physiological expression, making the separation technique useless as a diagnostic tool. In this protocol, we describe the functionalization and optimization of a surface for the cellular capture and release. This functionalized surface integrates biotinylated antibodies with a glass surface functionalized with an aminosilane (APTES), desthiobiotin and streptavidin. Cell release is facilitated through the introduction of biotin, allowing the recollection and purification of cells captured by the surface. This release is done through the targeting of the secondary moiety desthiobiotin, which results in a much more gentle release paradigm. This reduction in harsh reagents and shear forces reduces changes in cellular expression. The functionalized surface captures up to 80% of cells in a single cell mixture and has demonstrated 50% capture in a dual-cell mixture. Applications of this technology to xenografts and cancer separation studies are investigated. Quantification techniques for surface verification such as plate reader and ImageJ analyses are described as well.
个性化医疗的采用和发展的限制因素之一是无法开发诊断工具来探究患者之间表达的个体差异。目前试图分离细胞以填补这一空白的方法会导致生理表达的破坏,使得分离技术作为诊断工具毫无用处。在本方案中,我们描述了用于细胞捕获和释放的表面的功能化和优化。这种功能化表面将生物素化抗体与用氨基硅烷(APTES)、脱硫生物素和链霉亲和素功能化的玻璃表面整合在一起。通过引入生物素促进细胞释放,从而实现对表面捕获的细胞的回收和纯化。这种释放是通过靶向二级部分脱硫生物素实现的,这导致了一种更为温和的释放模式。苛刻试剂和剪切力的减少降低了细胞表达的变化。功能化表面在单细胞混合物中可捕获高达80%的细胞,在双细胞混合物中已证明捕获率为50%。研究了该技术在异种移植和癌症分离研究中的应用。还描述了用于表面验证的定量技术,如酶标仪和ImageJ分析。