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Electronic detection of ligand-receptor interactions

 

OHSU # 0574

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Summary:

Technology Overview: This biosensor technology enables the direct electrical detection of molecules in solution. Detection is accomplished by the simultaneous monitoring of several dielectric parameters – including capacitance, dissipation factor, conductance, impedance, and phase – over a selected alternating current frequency range. The resulting dielectric parameter/frequency patterns combine to form a unique “fingerprint” for the tested molecule. These patterns are sufficiently unique to identify unknown molecules in experimental samples from a database of known patterns.

Electrode composition can be altered to promote binding of various classes of biomolecules. For example, the inventors made the discovery that chromium electrodes tightly bind proteins without the necessity of specialized coatings. The chromium-based detector can be used to analyze single bound proteins or protein-ligand interactions.

In vitro diagnostics are a natural use for the technology. Detection of antigens such as viruses and bacteria is critical for medical diagnoses. Direct electrical sensing is rapid, with start-to-finish assay times of 10-20 minutes. The current enzyme-linked immunosorbent assays (EIA-based assays) and immunoradiometric assays used commonly in in vitro diagnostics take several hours and tend to be tedious and expensive. Direct electrical detection allows testing for antigens early in the infection cycle. Furthermore, multiplexing is straightforward with this technology. Many independent diagnostic tests can be performed simultaneously, each detecting multiple antigens for greater sensitivity and accuracy.

Direct electrical detection has advantages in the research laboratory as well. Current protein-ligand detection technologies – such as surface plasmon resonance spectrometry, optical interferometry, and quartz crystal microbalancing – do not provide the ability to identify the particular ligand being bound. They also depend on special coatings to promote protein binding, which can contribute significant batch-to-batch error. And finally, they rely on specialized detection equipment, making them expensive choices for academic and start-up labs. Direct electrical detection identifies unknowns, has uniform protein binding characteristics, and can be analyzed on inexpensive personal computers.

This biosensor technology provides a novel bioelectrical analyzer system that consists of: i) a silicon substrate, ii) an electrode having an exposed chromium surface, iii) a biomolecular probe, iv) a stimulator electrically coupled to the electrode, v) a detector, and vi) a means for comparing the sample signal profile with a reference signal profile.

Market Summary: In vitro diagnostic testing is a burgeoning segment of the healthcare industry. The segment had $38b in global sales in 2007, with approximately 6.8% year-over-year growth. North America, Europe and Japan represent over 90% of these sales.

Future Research: Further testing of electrical parameter monitoring combinations will optimize ligand binding pattern recognition for desired targets. This testing will guide further chip design and software refinements on the path to commercialization.

Patent Status: Issued US patent 7,214,528 covers the biosensor apparatus. Issued US patent 7,732,140 covers the methods for using the biosensor.

The biosensor and methods for using the biosensor are also covered by Canadian patent 2,512,378 and Australian patent 2003303600.

Patent applications are pending in Europe and Israel.

Licensing Opportunity: Technology #574 is available for licensing or collaborative development.

Patents:

IssuedUnited States7,214,528
IssuedIsrael
IssuedUnited States7,732,140

For more information, contact:

Arvin Paranjpe
Technology Development Manager
503-494-3210