The challenge:

As the genetic origins and the molecular basis of disease become clearer with the conclusion of the Human Genome Project and the accompanying explosion in molecular biology insights, it becomes obvious that devices based on DNA chips will be used for all kinds of applications. The biggest challenges in positioning oneself in the forefront of this exploding area of activity consist in encountering methods for arraying (selectively depositing distinct oligonucleotide probes at high density) and detecting the hybridisation event. The BBG is developing exclusive competitive technologies to do both.

The applications:

An annual market of more than $500 million already exists although the tools are not yet perfected. This market is distributed among:

Gene discovery: sequencing, proteomics, genomics.
Disease diagnosis
Drug discovery: to find correlations between therapeutic responses to drugs and the genetic profiles of patients. Toxicological research: to evaluate toxicological index with simple in vitro expression vectors.
Diagnostics: the biggest yet untappered market is the diagnostics market. No system is of low enough cost today to combine a microsystems approach with the power of hybridisation specificity. Yet, it is certain that human, plant, animal, and industrial diagnostics will be more reliable in a few years if they are based on DNA. Can it be done so cheaply as to even be disposable?

Our technology:
We offer an integrated approach to arraying and detection. We have proven and are optimising an electrochemical method for the deposition of the distinct probes that are prefabricated (and quality controlled) with photolithographic resolution. Our system is similar to the Hyseq concept (left) but much more generic, selective and easy to use. The method can be used not only for DNA chip arraying but also for the production of any multisensor array be it based on oligonucleotide hybridisation, catalysis, or affinity interactions.

The very same set up that is used for the arraying, is also used for the electrochemical detection. The goal is to use the system for the one-step hybridisation and detection of the event without need for labeling and with unprecendented sensitivities. The electrochemical detection is used in combination with hybridisation on solid state or in solution to increase  specificity  and  lower  the  detection limits. When incorporated in microsystems, the labels do not need to exist on the target, making therefore the device applicable directly after a DNA extraction procedure (NO PCR AMPLIFICATION). Some ideas for the detection schemes are shown below.


Schematic of direct transduction using HRP label