Lenhart Ashley E, Kennedy Robert T
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Meas Sci Au. 2023 Aug 24;3(5):380-389. doi: 10.1021/acsmeasuresciau.3c00025. eCollection 2023 Oct 18.
Microfluidic devices are becoming an important tool for bioanalysis with applications including studying cell secretion, cell growth, and drug delivery. Small molecules such as drugs, cell products, or nutrients may partition into polydimethylsiloxane (PDMS), a commonly used material for microfluidic devices, potentially leading to poor recovery or inaccurate delivery of such chemicals. To decrease small-molecule partitioning, surface and bulk PDMS treatments have been developed; however, these have been tested on few analytes, or their biocompatibility are unknown. Studies often focus on one analyte, whereas a diversity of chemicals are of interest and possibly affected. In this study, 11 device treatments are tested and applied to 21 biologically relevant small molecules with a variety of chemical structures. Device treatments are characterized using water contact angle measurements and evaluated by measuring recovery of the 21 target analytes using liquid chromatography-mass spectrometry. 1,5-Dimethyl-1,5-diazaundecamethylene polymethobromide (polybrene), a positively charged polymer, produced the least hydrophilic surface and was found to provide the best recovery with most of the analytes having >50% recovery and up to 92% recovery; however, recovery varied by analyte highlighting the importance of analyte diversity rather than targeting a single analyte in evaluating treatments. A polybrene-treated device was applied to investigate secretion from pancreatic islets, which are micro-organs involved in glucose homeostasis and diabetes. Islets secrete small molecules that have been shown to modulate the secretion of islets' main functional products, glucose-regulating hormones. The polybrene treatment enabled the detection of 20 target analytes from islets-on-chip during isosmotic and hypo-osmotic glucose perfusions and resulted in detection of more significant secretion changes compared to untreated PDMS.
微流控设备正成为生物分析的重要工具,其应用包括研究细胞分泌、细胞生长和药物递送。药物、细胞产物或营养物质等小分子可能会分配到聚二甲基硅氧烷(PDMS)中,PDMS是微流控设备常用的材料,这可能导致此类化学物质的回收率低或递送不准确。为了减少小分子的分配,已经开发了表面和本体PDMS处理方法;然而,这些方法仅在少数分析物上进行了测试,或者其生物相容性未知。研究通常只关注一种分析物,而实际上有多种化学物质令人感兴趣且可能受到影响。在本研究中,测试了11种设备处理方法,并将其应用于21种具有各种化学结构的生物相关小分子。通过测量水接触角来表征设备处理方法,并使用液相色谱 - 质谱法测量21种目标分析物的回收率来评估这些方法。1,5 - 二甲基 - 1,5 - 二氮杂十一亚甲基多溴化铵(聚凝胺),一种带正电荷的聚合物,产生的表面亲水性最低,并且发现它能为大多数分析物提供最佳回收率,大多数分析物的回收率>50%,最高可达92%;然而,不同分析物的回收率有所不同,这突出了在评估处理方法时分析物多样性的重要性,而不是只针对单一分析物。将经过聚凝胺处理的设备用于研究胰岛的分泌,胰岛是参与葡萄糖稳态和糖尿病的微器官。胰岛分泌的小分子已被证明可调节胰岛主要功能产物(调节血糖的激素)的分泌。聚凝胺处理使得在等渗和低渗葡萄糖灌注过程中能够从芯片上的胰岛中检测到20种目标分析物,并且与未处理的PDMS相比,检测到了更显著的分泌变化。