The bulk cell population response to a stimulus, be it a growth factor or a cytotoxic agent, neglects the cell-to-cell variability that can serve as a friend or as a foe in human biology. Biochemical variations among closely related cells furnish the basis for the adaptability of the immune system but also act as the root cause of resistance to chemotherapy by tumors. Consequently, the ability to probe for the presence of key biochemical variables at the single-cell level is now recognized to be of significant biological and biomedical impact. Chemical cytometry has emerged as an ultrasensitive single-cell platform with the flexibility to measure an array of cellular components, ranging from metabolite concentrations to enzyme activities. We briefly review the various chemical cytometry strategies, including recent advances in reporter design, probe and metabolite separation, and detection instrumentation. We also describe strategies for improving intracellular delivery, biochemical specificity, metabolic stability, and detection sensitivity of probes. Recent applications of these strategies to small molecules, lipids, proteins, and other analytes are discussed. Finally, we assess the current scope and limitations of chemical cytometry and discuss areas for future development to meet the needs of single-cell research.

中文翻译：

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化学细胞计数传感器的设计与应用

大细胞群体对刺激的反应，无论是生长因子还是细胞毒性剂，都忽略了细胞间的可变性，而可变性可以作为人类生物学的朋友或敌人。密切相关的细胞之间的生化变化为免疫系统的适应性奠定了基础，但也成为肿瘤对化学疗法产生抗性的根本原因。因此，现在已经认识到在单细胞水平上探测关键生化变量的存在的能力具有重大的生物学和生物医学影响。化学细胞计数法已经成为一种超灵敏的单细胞平台，可以灵活地测量一系列细胞组分，范围从代谢物浓度到酶活性。我们简要回顾了各种化学细胞计数策略，包括报告基因设计的最新进展，探针和代谢物分离，以及检测仪器。我们还描述了改善细胞内递送，生化特异性，代谢稳定性和探针检测灵敏度的策略。讨论了这些策略在小分子，脂质，蛋白质和其他分析物中的最新应用。最后，我们评估化学细胞计数法的当前范围和局限性，并讨论未来的发展领域，以满足单细胞研究的需求。