Folding based Biosensors

For a while I have been planning to write about biosensors that have been called names like genetically encoded biosensors, protein complementation biosensors, folding based biosensors etc. The biological elements in these biosensors can be proteins, DNA, or aptamers. Binding of specific ligand induces a change in structure of the biological molecule resulting in a signal that can be optical or electrical. What finally triggered me to write about these types of biosensor is an excellent overview on folding based biosensor by Kevin W. Plaxco of UCSB.

In this post I will only talk about folding based biosensors and will touch on other biosensors in later posts. To best understand folding based biosensors take a look at the schematic that I got from Prof. Plaxco website.

Credit: Prof. Kevin W. Plaxco; University of California. Santa Barbara

The DNA/aptamer probe is modified with the redoxable methylene blue (MB) moiety at one end (other tags can be used too!), and is attached to the gold working electrode at the other end via gold-thiol linkage. Upon target binding, the probe can either fold so that MB comes close to the electrode, increasing the efficiency of electrons transfer from the MB tag to the electrode, thereby producing proportional increase in current. It can also happen other ways where probe is already folded and will unfold on binding of target hence decreasing the current. These sensors are essentially label free sensors.

Want to know more about these sensors? I have put links to publications that I found on Google Scholar

  1. Reagentless transduction of DNA hybridization into a readily detectable electrochemical signal

2003 paper in PNAS describing the concept of folding based biosensors for picomolar level detection of DNA

  1. Monitoring of Cocaine using Electrochemical Aptamer-Based Sensor

2009 paper in JACS on detecting low micromolar level cocaine detection using folding based biosensors integrated with microfluidics.

  1. Optical Sensors Based on the Binding-Induced Folding of Proteins and Polypeptides

2009 paper in Chemistry describing folding based biosensors inducing change in optical properties rather than electrical properties

  1. Better Living Through Biosensors

A really nice powerpoint presentation by Prof. Plaxco

As I was writing about this post I thought of my previous post on multiplexed CombiMatrix platform. Hey! can this biosensor be put on Combimatrix platform-will be a cool technology!


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