Abstract
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.
Highlights
Various modes of inquiry in biology and chemistry can be characterized as “digital.” Within the context of microfluidics, two broad areas of research are especially relevant and have shaped how the authors view the emerging disciplines of digital biology and chemistry: (i) the study of switching in natural systems (Fig. 1A) and (ii) the study of single biological entities (Fig. 1B)
We focus on digital biology and chemistry in the context of the two areas of research mentioned above and describe these digital approaches primarily in terms of how we have experienced and approached them through our own research
“digital” can refer to the tendency of many natural systems to switch between discrete states in response to specific signals such as proteins, carbohydrates, nucleic acids, autoinducers, or redox potential gradients
Summary
Various modes of inquiry in biology and chemistry can be characterized as “digital.” Within the context of microfluidics, two broad areas of research are especially relevant and have shaped how the authors view the emerging disciplines of digital biology and chemistry: (i) the study of switching in natural systems (Fig. 1A) and (ii) the study of single biological entities (Fig. 1B). An analog chemical signal can be translated into a series of digital yes-or-no bits to indicate whether biomarkers in a sample exceed known threshold concentrations, enabling microfluidic devices to perform measurements of clinically relevant changes in concentration of biomarkers.[2] time control provided by microfluidics can enable “digitizing” reactions in time, instead of space: in one example, this approach was used to construct a chemical amplification network.[16] microfluidic technology has a number of limitations as well.
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