Shulman Matthew, Mathew Thomas, Trivedi Aria, Gholizadeh Azam, Colcord Charlotte, Wiley Ryan, Allen Kiron S, Thangam Lakshmi, Voss Kelsey, Abbyad Paul
Department of Chemistry and Biochemistry, Santa Clara University, Santa Clara, CA, 95053, USA.
Department of Pharmacology, University of Virginia, Charlottesville, VA, 22903, USA.
Lab Chip. 2025 Jan 28;25(3):383-392. doi: 10.1039/d4lc00792a.
We present here a passive and label-free droplet microfluidic platform to sort cells stepwise by lactate and proton secretion from glycolysis. A technology developed in our lab, Sorting by Interfacial Tension (SIFT), sorts droplets containing single cells into two populations based on pH by using interfacial tension. Cellular glycolysis lowers the pH of droplets through proton secretion, enabling passive selection based on interfacial tension and hence single-cell glycolysis. The SIFT technique is expanded here by exploiting the dynamic droplet acidification from surfactant adsorption that leads to a concurrent increase in interfacial tension. This allows multiple microfabricated rails at different downstream positions to isolate cells with distinct glycolytic levels. The device is used to correlate sorted cells with three levels of glycolysis with a conventional surface marker for T-cell activation. As glycolysis is associated with both disease and cell state, this technology facilitates the sorting and analysis of crucial cell subpopulations for applications in oncology, immunology and immunotherapy.
我们在此展示了一种被动且无标记的液滴微流控平台，用于通过糖酵解产生的乳酸和质子分泌对细胞进行逐步分选。我们实验室开发的一种技术，即界面张力分选法（SIFT），通过利用界面张力将含有单细胞的液滴按pH值分为两个群体。细胞糖酵解通过质子分泌降低液滴的pH值，从而实现基于界面张力的被动分选，进而实现单细胞糖酵解分析。在此，通过利用表面活性剂吸附导致的动态液滴酸化，进而引起界面张力同时增加，对SIFT技术进行了扩展。这使得在不同下游位置的多个微加工轨道能够分离具有不同糖酵解水平的细胞。该装置用于将分选后的细胞与三种糖酵解水平与T细胞激活的传统表面标志物进行关联。由于糖酵解与疾病和细胞状态都有关联，这项技术有助于对关键细胞亚群进行分选和分析，以应用于肿瘤学、免疫学和免疫治疗领域。
