Interfacing microfluidics with information-rich detection systems for cells, bioparticles, and molecules

The development of elegant and numerous microfluidic manipulations has enabled significant advances in the processing of small volume samples and the detection of minute amounts of biomaterials. Effective isolation of single cells in a defined volume as well as manipulations of complex bioparticle or biomolecule mixtures allows for the utilization of information-rich detection methods including mass spectrometry, electron microscopy imaging, and amplification/sequencing. The art and science of translating biosamples from microfluidic platforms to highly advanced, information-rich detection system is the focus of this review, where we term the translation between the microfluidics elements to the external world “off-chipping.” When presented with the challenge of presenting sub-nanoliter volumes of manipulated sample to a detection scheme, several delivery techniques have been developed for effective analysis. These techniques include spraying (electrospray, nano-electrospray, pneumatic), meniscus-defined volumes (droplets, plugs), constrained volumes (narrow channels, containers), and phase changes (deposition, freezing). Each technique has been proven effective in delivering highly defined samples from microfluidic systems to the detection elements. This review organizes and presents selective publications that illustrate the advancements of these delivery techniques with respect to the type of sample analyzed, while introducing each strategy and providing historical perspective. The publications highlighted in this review were chosen due to their significance and relevance in the development of their respective off-chip technique. GRAPHICAL ABSTRACT: This review highlights advancements of delivery methods off a microfluidic chip for additional information rich detection schemes [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00216-022-04043-1.