We are designing and fabricating a stable, fully-enclosed biosensor that uses ion channel proteins as the signal transfuction mechanisms.  The device consists of 4 or 8 individually-adressable wells in which ion channels are assembled and which yield DC current measurements to an attached amplifier.

 

The goals are two-fold: first, to perform basic molecular biology and mutagenesis to create ion channels that are useful in sensors for life detection and health monitoring.   Second, to develop these engineered channels into stable biosensors, using MEMS technology and biomimetic lipid membranes. The advantages of the current design over existing ion channel biosensors are (1) increased stability due to the agarose layer; (2) reduced electrical noise due to the thick dielectric, which is constructed from a particular photoresist; (3) ability to incorporate any type of channel, not only gramicidin; and (4) the use of a large reservoir, which allows for DC current measurements.


Ion channels yield very sensitive and specific signals to a wide array of ligands.  They thus would be ideal bases for biosensors if they could be stably expressed and addressed.   However, ion channels only function within biological or "biomimetic" membranes, whose lifespan is usually several hours or less.   Additionally, their small signals (1-10 picoamps) make a low-noise, highly amplified detection platform necessary.   Because of these complications, ion channels have not yet been made into widespread commercial devices.

 

device image device image




Our collaborators are:

Design and testing: Dennis Dougherty , Joshua Maurer, Caltech
                               Ion Channel Mutagenesis: Hagan Bayley , Texas AMU
                               Astrobiology life signature definition: Alexandra MacDermott, University of Clear Lake
                               Gift of GlyR: Michael Cascio, University of Pittsburgh Pittsburgh

Here are some single-channel recordings from human glycine receptor expressed in the device:

GlyRTraces