By Salvatore Salamone
September 9, 2002 | Vialogy Corp. and Genicon Sciences, two relatively young California companies, have taken very different approaches to address the same problem: how to extract biologically significant information on a microarray when relatively few molecules or genes are involved.
The two companies recently announced promising technologies to get more usable information from microarrays.
The problem their technologies address stems from the way microarrays are scanned and read. Typically, genes of interest [i.e. active genes in a cancer cell] are first isolated and copied. Then nucleotides with fluorescent dye are added to the relevant genes.
The genes are spread on the microarray’s surface and stick to probes with complementary DNA sequences. The microarray is washed to remove genes that did not bind to the probes and then the array is illuminated with a laser causing the fluorescent dye in the remaining genes to glow and emit a signal.
Today, tens of thousands to millions of genes are placed on microarray spots containing 20 million to 30 million probes each. If a gene and probe are the right match, it is likely there will be many interactions where genes bind to probes in a single location. The more bindings within a particular spot, the greater the signal coming from that location.
A scanner is used to detect the signal, and therein lies the problem: All electrical and optical systems produce background noise.
“Systems that read the information off of microarrays look at either an optical or electrical signal coming from the microarray,” says Douglas Lane, Vialogy CEO and president. “If relatively few genes bind [in a single spot on the array], the signal may be too weak to be detected. The challenge with microarrays is to find a very weak signal within (the) background noise.”
To detect weak signals in the background noise, Vialogy has developed signal processing techniques based on quantum resonance interferometry that helps extract information that might otherwise go undetected from microarrays. Vialogy claims its techniques will enable instruments to detect signals that are up to 10,000 times weaker than the level of background noise.
The calculations that must be performed before this information can be extracted requires a lot of computational horsepower. “We crashed a number of 32-bit systems,” says Lane. To address this issue, Intel Corp. and Vialogy recently announced a collaboration that makes Vialogy an early Itanium Processor family developer collaborator. As part of this collaboration, Vialogy recieved early Itanium 2 production computers from Intel.
Vialogy has several patents on its quantum resonance interferometry signal processing technologies and is developing an enterprise version of its technology for drug discovery.
Genicon Sciences is taking a different approach to getting more usable data from microarrays. Rather than trying to find a weak signal coming from a microarray’s surface, Genicon’s approach is to amplify the emitted signal.
The company recently announced the One-Color Microarray Toolkit, a detection system based on non-flourescent technology. The heart of Genicon Sciences’ product is a signal generation and detection technology called Resonance Light Scattering (RLS). Rather than using fluorescent dyes, nano-sized particles called RLS particles are used as labels within genes to detect biological interactions on an array.
To read an array, white light is shined on the surface. The RLS particles within the gene absorb the light and emit light of their own. According to the company, the light signal generated by an RLS particle is 10,000 to a million times greater than with the fluorescent dye approach, making the signal is much easier to detect.
Both companies’ approaches might be useful over the next few years as arrays become more miniaturized.
New nanotechnologies hold the promise of being able to create arrays that pack orders of magnitude of more finely shaped probes within the same surface area used today (see The Incredible Shrinking Microarray, page 30). For nanotechnologies to be exploited, highly sensitive detection will be critical.