Microfluidics: smaller, faster, better
Making waves with microfluidics
One of the key developments in biotechnology within the past decade is clearly the miniaturiation of many laboratory techniques, especially bioassays and methods for molecular synthesis and separation. In addition to advantages provided by the plethora of microwell- and bead-based technologies, the rise of microfluidic platforms in particular has ushered in an exciting era of microscale biology. In this new world of the ultra-small, an important challenge will be for biologists and technologists to closely collaborate in the design and optimisation of microfluidic lab-on-chip systems that represent robust, biomedically relevant assays.
Writing recently in Nature Reviews in Drug Discovery, Petra Dittrich and Andreas Manz, both of the ISAS Institute for Analytical Sciences in Dortmund, Germany, summarise the latest developments in the field of microfluidics, with a particular focus on the impact of lab-on-a-chip systems for drug discovery. Of particular interest, novel applications using microfluidics have recently been developed that have no conventional equivalent at the macroscopic level, highlighting the potential of microfluidic platforms to achieve important technological breakthroughs that can impact both basic biology and drug discovery.
In one such elegant application, a team led by Sunney Xie, of the Department of Chemistry and Chemical Biology at Harvard University, recently described in Nature their observations of low-level protein expression in individual cells. Using a microfluidic chip-based approach, they were able to analyse stochastic expression of various proteins at the level of single molecules. Previous approaches to study stochastic protein expression have largely been limited to indirect observations, primarily because of the need to work with larger numbers of cells and the lack of synchronisation between these cells. Also, prior analyses of single cells were unable to achieve the sensitivity required for the detection of individual events of protein production.
In their report, the authors show that their microfluidic system-based assay is capable of real-time measurement of β-galactosidase expression in living bacteria at the level of single molecules. The method was also applied to yeast cells and murine embryonic stem cells with comparable results. Given the large number of low copy number proteins, many of which are therefore currently not accessible through standard genomic and proteomic methods, this novel technique for the analysis of single cell gene expression is an important new development that will facilitate the systematic, genome-wide characterisation of these types of molecules.
A related area of innovation is in the actual fabrication of microfluidic chips. To enable the generation of data that can reliably be compared between laboratories, standardisation in the manufacturing process of such devices will be an increasingly important area of activity in the coming years. Towards this end, Faisal Shaikh and Victor Ugaz, both of the Department of Chemical Engineering of Texas A&M University, recently describe in PNAS their approach for the sequential concentration of DNA using microfluidic chips incorporating individually addressable microelectrodes. This technique may be useful for the manufacture of several types of microfluidic chips, as methods more efficient than currently available sample-injection technologies are urgently needed for the precise handling of very small amounts of biomolecules such as DNA, proteins, or peptides.
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