Instrumentation and Measurement Physics(DIMP)
Physique des instruments et mesures (DPIM)
Ulrich KRULL
University of Toronto at Missisauga
Genomic target identification using imaging of distributed gradients of oligonucleotide probes in conjunction with microfluidics
The detection of nucleic acids using biosensors and microarray chips is now used in many applications such as forensic identification, screening of genomes for mutations, and detection and identification of bacteria and viruses. One important finding is that the control of the density of immobilized single stranded probe molecules can be used to tune selectivity to facilitate detection of even single base pair mismatches. The results are now being implemented to develop new device technologies. One approach provides for a multi-dimensional distribution of selective chemistry at a surface, but in such a way that the coatings of probe molecules are continuous, and operate to provide gradients of selectivity in one or more directions. Such a Gradient Resolved Information Platform (GRIP), is based on a surface that is coated with a continuous gradient of density and/or sequence and/or orientation and structure of ssDNA. The location, extent of hybridization, and speed of hybridization on such a surface by a target sequence can be used to identify and quantitatively measure the target. The goal of this research is to combine quantitative microfluidics using electrokinetic flow with this novel form of biochip to create a quantitative sensing system that is suitable for concurrent rapid analysis of multiple nucleic acid targets. We are developing a microfluidics package that quantitatively delivers target oligonucleotide to a GRIP chip, with detection of hybridization being done in pseudo-real-time using epi-fluorescence, confocal fluorescence and time-resolved fluorescence methods.