Harnessing the ability to precisely and reproducibly actuate fluids and manipulate bioparticles such as DNA, cells, and molecules at the microscale, microfluidics is a powerful tool that is currently revolutionizing chemical and biological analysis by replicating laboratory bench-top technology on a miniature chip-scale device, thus allowing assays to be carried out at a fraction of the time and cost while affording portability and field-use capability. Emerging from a decade of research and development in microfluidic technology are a wide range of promising laboratory and consumer biotechnological applications from microscale genetic and proteomic analysis kits, cell culture and manipulation platforms, biosensors, and pathogen detection systems to point-of-care diagnostic devices, high-throughput combinatorial drug screening platforms, schemes for targeted drug delivery and advanced therapeutics, and novel biomaterials synthesis for tissue engineering. The developments associated with these technological advances along with their respective applications to date are reviewed from a broad perspective and possible future directions that could arise from the current state of the art are discussed.

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Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.

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The confined internal space of a liquid marble, as well as its porous and non-adhesive shell, offers an attractive application possibility - accommodating living cells inside liquid marbles. Cancer cells in suspension may aggregate to form three dimensional structures, also known as cancer cell spheroids (CCS). In this study, CCS formation inside liquid marble is investigated. This liquid marble application opens significant and novel avenues for biomedical applications and cancer research.

A liquid marble micro-bioreactor is prepared by placing a drop of murine embryonic stem cell (ESC) (Oct4B2-ESC) suspension onto a polytetrafluoroethylene (PTFE) particle bed. The Oct4B2-ESC aggregates to form embryoid bodies (EBs) with relatively uniform size and shape in a liquid marble within 3 d. For the first time, the feasibility of differentiating ESC into cardiac lineages within liquid marbles is being investigated. Without the addition of growth factors, suspended EBs from liquid marbles express various precardiac mesoderm markers including Flk-1, Gata4, and Nkx2.5. Some of the suspended EBs exhibit spontaneous contraction. These results indicate that the liquid marble provides a suitable microenvironment to induce EB formation and spontaneous cardiac mesoderm differentiation. Some of the EBs are subsequently plated onto gelatin-coated tissue culture dishes. Plated EBs express mature cardiac markers atrial myosin light chain 2a (MLC2a) and ventricular myosin light chain (MLC2v), and the cardiac structural marker α-actinin. More than 60% of the plated EBs exhibit spontaneous contraction and express mature cardiomyocyte marker cardiac troponin T (cTnT), indicating that these EBs have differentiated into functional cardiomyocytes. Together, these results demonstrate that the liquid-marble technique is an easily employed, cost effective, and efficient approach to generate EBs and facilitating their cardiogenesis.