Publications

Short non-coding RNAs as bacteria species identifiers detected by surface plasmon resonance enhanced common path interferometry
Charles Greef, Viatcheslav Petrapavlovskikh, Oyvind Nilsen, Boris Khattatov, Mikhail Plam (BiOptix, LLC); John Hall, (Hall Stable Lasers, LLC)
Proceedings of SPIE, Defense and Security Conference, Orlando, Florida, March 17-20 2008
Abstract:
Small non-coding RNA sequences have recently been discovered as unique identifiers of certain bacterial species, raising the possibility that they can be used as highly specific Biowarfare Agent detection markers in automated field deployable integrated detection systems. Because they are present in high abundance they could allow genomic based bacterial species identification without the need for pre-assay amplification. Further, a direct detection method would obviate the need for chemical labeling, enabling a rapid, efficient, high sensitivity mechanism for bacterial detection. Surface Plasmon Resonance enhanced Common Path Interferometry (SPR-CPI) is a potentially market disruptive, high sensitivity dual technology that allows real-time direct multiplex measurement of biomolecule interactions, including small molecules, nucleic acids, proteins, and microbes. SPR-CPI measures differences in phase shift of reflected S and P polarized light under Total Internal Reflection (TIR) conditions at a surface, caused by changes in refractive index induced by biomolecular interactions within the evanescent field at the TIR interface. The measurement is performed on a microarray of discrete 2-dimensional areas functionalized with biomolecule capture reagents, allowing simultaneous measurement of up to 100 separate analytes. The optical beam encompasses the entire microarray, allowing a solid state detector system with no scanning requirement. Output consists of simultaneous voltage measurements proportional to the phase differences resulting from the refractive index changes from each microarray feature, and is automatically processed and displayed graphically or delivered to a decision making algorithm, enabling a fully automatic detection system capable of rapid detection and quantification of small nucleic acids at extremely sensitive levels. Proof-of-concept experiments on model systems and cell culture samples have demonstrated utility of the system, and efforts are in progress for full development and deployment of the device. The technology has broad applicability as a universal detection platform for BWA detection, medical diagnostics, and drug discovery research, and represents a new class of instrumentation as a rapid, high sensitivity, label-free methodology. Keywords: Biowarfare agent, bacteria, microarray; microRNA, small RNA, SPR, common path interferometry    

Polarization-based Interferometric Detector
Hall, J.L.; Petropavlovskikh, S.; Nilsen, O.
US Patent 7,233,396 filed by Wilson Sonsini Goodrich & Rosati on April 17, 2006; issued on June 19, 2007.

Rapid, multiplexed, high-sensitivity detection of biowarfare agents by surface plasmon resonance enhanced common path interferometry
Charles Greef, Viatcheslav Petrapavlovskikh, Oyvind Nilsen, Bilge Hacioglu, Boris Khattatov, BiOptix, LLC; John Hall, Hall Stable Lasers, LLC
Chemical and Biological Sensing VIII, Proc. of SPIE, Vol. 6554, 2007
Abstract:
Real time monitoring of biowarfare agents for military and civilian protection remains a high priority for homeland security and battlefield readiness. Available devices have sensitivity adequate for BWA detection, but the detection modules have limited periods of deployment, require frequent maintenance, employ single-use disposable components, and have limited multiplexing capability. Surface Plasmon Resonance(SPR) Common Path Interferometry (CPI) is a label-free, high sensitivity biomolecule interaction measurement technology that allows multiplexed real-time measurement of biowarfare agents, including small molecules, proteins, and microbes. The technology permits continuous operation in a field deployable detection module of an integrated BWA monitoring system. SPR-CPI measures differences in phase shift of reflected S and P polarized light (under TIR conditions) at a surface, caused by changes in refractive index induced by biomolecular interactions within the evanescent field at the TIR interface. Download a copy of the presentation in PDF format.   

Detection and discrimination of low concentration gas contaminants by means of interferometrically-sensed polymers
Hall, J.L.; Petropavlovskikh, S.; Nilsen, O.; Hacioglu, B.
Sensors, 2005 IEEE Volume , Issue 30 Oct.-3 Nov. 2005 Page(s): 4 pp. -
Digital Object Identifier 10.1109/ICSENS.2005.1597962
Summary: Two optical techniques for bio- and chemical sensing were investigated. The methods are based on deviation of the optical properties of polymer transducers due to change in either index of refraction or dimension of the sensing element under molecular impact. The holographic interferometer technology developed at the University of Colorado observes interactions between an analyte and a transducer's surface and bulk. The second approach, a common path interferometer proposed by Dr. John Hall, focuses on surface interactions only. The two techniques complement each other, enabling the separation of surface and bulk interactions. This is critical for accurate description of chemical uptake and release dynamics, and therefore for obtaining parameters necessary for the analyte identification process. Preliminary sensitivity level of the systems is on the order of 10/sup -5/ RTU (refractive index units) with possible improvement down to 10/sup -7/ RTU. Read more... »