Witters Daan, Sun Bing, Begolo Stefano, Rodriguez-Manzano Jesus, Robles Whitney, Ismagilov Rustem F
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Lab Chip. 2014 Sep 7;14(17):3225-32. doi: 10.1039/c4lc00248b.
This account examines developments in "digital" biology and chemistry within the context of microfluidics, from a personal perspective. Using microfluidics as a frame of reference, we identify two areas of research within digital biology and chemistry that are of special interest: (i) the study of systems that switch between discrete states in response to changes in chemical concentration of signals, and (ii) the study of single biological entities such as molecules or cells. In particular, microfluidics accelerates analysis of switching systems (i.e., those that exhibit a sharp change in output over a narrow range of input) by enabling monitoring of multiple reactions in parallel over a range of concentrations of signals. Conversely, such switching systems can be used to create new kinds of microfluidic detection systems that provide "analog-to-digital" signal conversion and logic. Microfluidic compartmentalization technologies for studying and isolating single entities can be used to reconstruct and understand cellular processes, study interactions between single biological entities, and examine the intrinsic heterogeneity of populations of molecules, cells, or organisms. Furthermore, compartmentalization of single cells or molecules in "digital" microfluidic experiments can induce switching in a range of reaction systems to enable sensitive detection of cells or biomolecules, such as with digital ELISA or digital PCR. This "digitizing" offers advantages in terms of robustness, assay design, and simplicity because quantitative information can be obtained with qualitative measurements. While digital formats have been shown to improve the robustness of existing chemistries, we anticipate that in the future they will enable new chemistries to be used for quantitative measurements, and that digital biology and chemistry will continue to provide further opportunities for measuring biomolecules, understanding natural systems more deeply, and advancing molecular and cellular analysis. Microfluidics will impact digital biology and chemistry and will also benefit from them if it becomes massively distributed.
本文从个人视角审视了微流控背景下“数字”生物学和化学的发展。以微流控作为参照框架，我们确定了数字生物学和化学中两个特别有趣的研究领域：（i）研究因信号化学浓度变化而在离散状态之间切换的系统；（ii）研究诸如分子或细胞等单个生物实体。特别地，微流控通过在一系列信号浓度下并行监测多个反应，加速了对切换系统（即在狭窄输入范围内输出呈现急剧变化的系统）的分析。相反，此类切换系统可用于创建新型微流控检测系统，实现“模拟 - 数字”信号转换和逻辑功能。用于研究和分离单个实体的微流控分隔技术可用于重建和理解细胞过程、研究单个生物实体之间的相互作用，以及考察分子、细胞或生物体群体的内在异质性。此外，在“数字”微流控实验中对单个细胞或分子进行分隔，可在一系列反应系统中诱导切换，从而实现对细胞或生物分子的灵敏检测，如数字酶联免疫吸附测定法（digital ELISA）或数字聚合酶链反应（digital PCR）。这种“数字化”在稳健性、检测设计和简便性方面具有优势，因为可通过定性测量获得定量信息。虽然数字形式已被证明可提高现有化学方法的稳健性，但我们预计未来它们将使新的化学方法可用于定量测量，并且数字生物学和化学将继续为测量生物分子、更深入地理解自然系统以及推进分子和细胞分析提供更多机会。微流控将对数字生物学和化学产生影响，并且如果其能够大规模普及，也将从中受益。
