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Different aspects of microfluidics

Helene Andersson Svahn

The Nanobiotechnology group at the Royal Institute of Technology in Stockholm, Sweden, is focusing on interdisciplinary research combining nanotechnology and microfluidics with various biotechnology and medical applications. The research group consists of approximately 18 people with a wide variety of backgrounds such as electrical engineering, medical, biotechnology, chemistry and physics creating a very dynamic and interdisciplinary environment. We are currently focusing on four different areas, droplet microfluidics, microwell plates, paper-based microfluidics and clinical microfluidics.

The droplet microfluidic system was recently developed and is currently the only setup of its kind in Scandinavia. Thus far, we have developed a number of different assays including an assay for detection and analysis of cell surface protein biomarkers on individual human cells using enzymatic amplification inside microscale droplets. The method provides increased sensitivity with high throughput, and permits analysis of several cell samples concurrently by incorporation of droplet optical labels. This work was recognized in Nature Materials as a research highlight. We have also developed a fluorescence based homogeneous assay for protein analysis, passive separation of droplets by size based on cell-induced droplet shrinkage and improvements in robust and inexpensive microfluidic device fabrication for optical analysis. In March 2011 we had the first dissertation on droplet microfluidics in Scandinavia, addressing high throughput biological analysis.

droplet

Figure 1. Each droplet functions as an individual reaction vessel with volumes in the picoliter range.

 

 

We have also developed a microwell chip (672 wells of 500 nl) consisting of glass and silicon, with a spacing between wells that is compatible with automatic sorting of single cells into individual wells. This chip has been applied in many different biological studies, for example single leukemic non-adherent cancer cells were investigated for their heterogeneity in cell proliferation. The chip has subsequently also shown potential in protein analysis, mutation analysis by PCR, microfluidic integration and also for stem cell research. The combination of 1) the hundreds of experiments that can be run simultaneously in the chip and 2) the small volume per well saving reagent cost in molecule screens, makes the microwell chip a perfect match in cell research where high-throughput analysis is of utmost interest and the cellular effects of expensive molecules often are to be studied.

microwell

Fig 2. The microwell slide holding 672 wells optimized for cell based assays.


To overcome limitations for wide application of clinical microarrays, such as high cost of assays need for skilled technicians, need for advanced equipment and long assay times, our lab has developed two novel assay formats that allow for rapid, inexpensive, portable and easy to use microarray analysis. 1) Affinity-labelled superparamagnetic microparticles are actuated by magnetic fields to provide a detection technology which within seconds allows for a naked-eye or cell-phone camera analysis of microarray results with retained assay performance. 2) A paper-based substrate is used to create a lateral flow microarray assay which, together with affinity labeled gold nanoparticles allows for convenient ten-minute high density microarray assays and naked-eye or cell phone camera analysis. We hope that developments made by our group and others will be useful in translating the impressive advancement in lab-based diagnostic methods into integrated low-cost diagnostic devices amenable for field use, point of care, health care points and emergency medicine situations.

The clinical microfluidics team is focusing on applying engineering principles and technologies, especially micro-technology, to clinical medicine. The group expertise is within Bio-MicroElectroMechanical Systems with emphasis on sample preparation. Ongoing projects include the development of point-of-care blood diagnostics for bloodstream infectious diseases, host response to allergy and rare cell isolation for cancer diagnostics. The group is involved with several EU projects and currently coordinating one FP7 project, (highly integrated optical sensor for point-of-care label-free identification of pathogenic bacteria strains and their antibiotic resistance, www.intopsens.eu) and participates in two more projects, rapid point-of-care test platforms for infectious diseases (http://www.rapp-id.eu) and digital sequencing (www.digitalsequencing.eu).

Please visit the following link to see the full publication list of the Nanobiotechnology group, http://www.biotech.kth.se/nano_biotechnology/publications.html

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