Microcantilevers for Label-Free Biosensing

Cantilever as defined by Encyclopedia Britannica is a beam supported at one end and carrying a load at the other end or distributed along the unsupported portion. Place a load along the unsupported portion and cantilever will bend. Measure the bending or displacement and some information about the load can be determined. 

cantilever_stone

Cantilever rock formation

Shrink everything to really small sizes – a) replace hanging beam with micron sized silicon cantilevers, b) for load, imagine biomolecules  binding and interacting and c) for detecting minute displacement of beam, use lasers – and there is a label free  biosensors. Microcantilever based biosensors can detect biomolecular binding because of change in load and hence the displacement of the cantilever.  It is possible to design small devices with several of these microcantilevers in parallel using standard photolithography. This design flexibility allows several biomolecular binding events to be measured in parallel for high-throughput analysis. 

IBM researchers first presented this elegant approach in 2000(Science 288, 316-318, 2000) measuring specific binding of complementary DNA sequences and binary protein interaction. In 2001, sensitivity and specificity of microcantilever biosensor for detection of clinically relevant prostrate specific antigen (PSA) was demonstrated(Figure below from Nature Biotech, 19, 856-860, 2001).

 microcantilever_mazumdar Figure from Arun Mazumdar (Univ. California, Berkley)

Add to all this excitement, IBM’s  (www.zurich.ibm.com) further research on  based memory system that uses large arrays of microcantilevers to create holes in special polymers as binary code for memory. This raises the possibility of using same cantilevers for design of  multiplexed biosensing device capable of measuring 1000’s of  biomolecular interactions in parallel. No labels are required that makes this technology very attractive

Fast forward nine years, and the original IBM reasearch has been cited by 570 articles showing continued interest in this area. Two recent papers in Nature Nanotechnology takes this technology farther and explore the possibility of using dynamic mode (Nat. Nano. v-4, 179, 2009) and describe the percolative theory of binding(v-3, 691, 2008 ). Dynamic mode of measurement shall allow measurement under physiological conditions. Percolative mechanism on the other hand will lead to more sensitive bioassay.

Although very encouraging, it remains to be seen how these recent advances will help turn this elegant technology into usable biosensor ready to be used to answer relevant biological questions. To be a serious contender as a biosensor platform, this technology will have to be able to compete head-on with Biacore (www.biacore.com) now part of GE. Biacore is gold standard for bio-molecular interaction studies and to unseat this well established biosensing platform will take some serious efforts. Microcantilever based technologies will have to be cost effective, provide higher sensitivity or higher throughput.

Unfortunately at current state of art-microcantilever based biosensing technology is far from becoming a commercially attractive technology.

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One response to “Microcantilevers for Label-Free Biosensing

  1. Pingback: Self Assembled Monolayers (SAMs) on Gold: Celebrating 25 (or so) years! « All About Biosensors

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