AlphaSniffer says it has combined common path interferometry (CPI) and surface plasmon resonance (SPR) to create an instrument that can detect any specific molecular interaction in minutes. The company will be looking for beta test sites for the instruments at the US Department of Defense's SPIE Defense and Security Symposium in Atlanta, later this year. The new technology will initially be aimed at applications in research and academia laboratories, a market estimated to be worth in the region of $100m, as well as in homeland security and military markets ($350m). According to Dr Chad Greef, AlphaSniffer's senior scientist, the technology will also find application in drug discovery laboratories, such as in screening the binding of drug candidates to both desired and undesired targets. Meanwhile, the company is exploring the applicability of the system to study personalised genomic profiling of patient's drug responses. This could aid pharmaceutical companies resurrect drugs that have failed Phase III clinical trials due to efficacy only being observed in a limited genetic population. Another emerging problem the instrument may address is the problem of infectious influenza, where devices that can rapidly identify and track the bird flu epidemic will be needed to determine whether outbreaks are related or not. The instrument could also be used to test blood prior to transfusion for any contaminants such as HIV or hepatitis C and detecting pathogens such as the MRSA (methicillin-resistant Staphylococcus aureus) bacterium in operating rooms. According to Dr Misha Plam, AlphaSniffer CEO: "the technique works for label-free detection of any biomolecular interaction with a higher sensitivity than any other competing technology out there." He explained that the AlphaSniffer technology was developed by the unification of common path interferometry (CPI) and surface plasmon resonance (SPR) to yield the surface plasmon resonance-enhanced common path interferometer (SPR-CPI). SPR uses the excitation of surface plasmons, surface electromagnetic waves, by light to detect the adsorption of DNA or proteins on a silver or gold surface. Fast multiplex analysis of molecular interactions using the highly sensitive label-free SPR approach has previously been impossible, but has been enabled by AlphaSniffer's technology. Common path interferometry eliminates many sources of environmental drift and noise, which often detract from the utility of other interferometric approaches, since the reference beam and sample beam are the same. The instrument utilizes phase changes in a bipolarized laser beam as opposed to the more commonly used angle shift and intensity, which are limited by resolution issues and complex signal processing algorithms. Dr John Hall, AlphaSniffer's chief scientific advisor and the 2005 Physics Nobel Laureate, developed the concept of SPR-CPI in response to the demand for a fast, accurate and sensitive technique. This technique can be used to measure the binding constant between two species, one of which is coated to the surface of a biochip using standard contact or non-contact microarray deposition technology. Because the instrument interrogates the two-dimensional surface of the biochip in a spatially resolved way, it is possible to look at over 100 features per chip, with some redundancy needed for data validation. Each feature on the array will be about 150 microns in diameter The instrument currently has a sensitivity of 5x10-7 refractive index units (RIU), which roughly translates to 0.5 picograms of substance bound to each square millimeter. The instrument is about the size of a shoebox and is very robust. While the technique is not yet as sensitive as the enzyme-linked immunosorbent assays (ELISA) used in immunology to detect the presence of antibodies or antigens in a sample, it does offer considerable savings in time and efficiency. An ELISA may take several hours to identify Escherichia coli whereas the SPR-CPI measurement would be complete within 10 minutes.
