Department of Chemistry and Biochemistry, University of Hull, Hull, HU6 7RX, UK.
Department of Biomedical Sciences, University of Hull, Hull, HU6 7RX, UK.
Adv Biosyst. 2020 Nov;4(11):e2000054. doi: 10.1002/adbi.202000054. Epub 2020 Oct 5.
New techniques are required for earlier diagnosis and response to treatment of pancreatic cancer. Here, a label-free approach is reported in which circulating pancreatic tumor cells are isolated from healthy peripheral blood cells via cell bioimprinting technology. The method involves pre-fabrication of pancreatic cell layers and sequential casting of cell surfaces with a series of custom-made resins to produce negative cell imprints. The imprint is functionalized with a combination of polymers to engineer weak attraction to the cells which is further amplified by the increased area of contact with the matching cells. A flow-through bioimprint chip is designed and tested for selectivity toward two pancreatic tumor cell lines, ASPC-1 and Mia-PaCa-2. Healthy human peripheral blood mononuclear cells (PBMCs) are spiked with pancreatic tumor cells at various concentrations. Bioimprints are designed for preferential retention of the matching pancreatic tumor cells and with respect to PBMCs. Tumor bioimprints are capable of capturing and concentrating pancreatic tumor cells from a mixed cell population with increased retention observed with the number of seedings. ASPC-1 bioimprints preferentially retain both types of pancreatic tumor cells. This technology could be relevant for the collection and interrogation of liquid biopsies, early detection, and relapse monitoring of pancreatic cancer patients.
需要新的技术来实现对胰腺癌的早期诊断和治疗反应。在这里,报道了一种无标记的方法,通过细胞生物印迹技术从健康的外周血细胞中分离出循环胰腺肿瘤细胞。该方法涉及预先制作胰腺细胞层,并通过一系列定制的树脂对细胞表面进行顺序铸造,以产生负细胞印迹。印迹通过聚合物的组合进行功能化,以设计对细胞的弱吸引力,通过与匹配细胞的接触面积的增加进一步放大这种吸引力。设计并测试了一种用于两种胰腺肿瘤细胞系(ASPC-1 和 Mia-PaCa-2)的选择性的流通式生物印迹芯片。将健康的人外周血单核细胞(PBMC)与不同浓度的胰腺肿瘤细胞混合。生物印迹的设计目的是优先保留匹配的胰腺肿瘤细胞,同时相对于 PBMC 而言。肿瘤生物印迹能够从混合细胞群中捕获和浓缩胰腺肿瘤细胞,并且随着接种物数量的增加,保留率也会增加。ASPC-1 生物印迹优先保留两种类型的胰腺肿瘤细胞。这项技术可能与液体活检的采集和检测、胰腺癌患者的早期检测和复发监测有关。