Two of the three molecular architectures used in the Berkeley Lab colorometric biosensors are (a) polydiacetylene thin films on solid supports and (b) polydiacetylene liposomes. Please click on the image for a larger view.

APPLICATION OF TECHNOLOGY:

• Rapid test kits for influenza and other diseases
  
• Simple detection of E. coli and other bacteria in foods or on surfaces
• Drug development and improvement
• Detection of DNA hybridization
  
• Detecting pollutants

DEMONSTRATED DETECTION:

Influenza, E. coli, cholera toxin, biocatalysts, antibodies

POTENTIAL DETECTION:

Sexually transmitted diseases, polio and small pox, cholesterol, lipid and triglyceride levels, insulin blood levels, malaria, and others

ADVANTAGES:

• Detection can be carried out by a lay person under ambient conditions
  
• Yields rapid results and should be inexpensive to produce
  
• Can be miniaturized
• Enables identification of practically all strains of a virus or bacteria
  
• Enables sensitivity and specificity control
  
• Allows quantification of an analyte

ABSTRACT:

Researchers at Berkeley Lab have developed colorimetric biosensors that can be used by a lay person for simple detection of viruses, bacteria, parasites and other pathogens. These biopolymeric materials can also be used for drug development, detecting pollutants, DNA hybridization detection, screening reaction inhibitors, and a wide range of other applications.

The assays and biosensors devised by Deborah Charych, Quan Cheng, Jon Nagy, and Raymond Stevens are engineered membranes that mimic cell surfaces. They consist of biologically or chemically specific receptor ligands attached to a polydiacetylene backbone. Ligands may include nucleic acids, proteins, antibodies, carbohydrates, gangliosides, peptides, enzymes, or small molecules. The membranes change color when they undergo events that disrupt them. Such events are caused by molecular recognition between ligands and target analytes. The intensity of the color change allows quantification of the analyte’s concentration.

The Berkeley Lab biosensors allow direct detection with reasonably small amounts of analyte. Like conventional immunoassays, they are able to detect biological molecules, but unlike immunoassays they can provide specific detection with ligands other than antibodies.

Architectures
The Berkeley Lab technology can be used to create films on solid supports or to form liposomes. Collaborative research between Berkeley Lab scientists and Sandia National Laboratory produced materials that can be encapsulated in sol-gel. Sol-gel encapsulation immobilizes the biopolymeric material and the resulting composite can be easily applied to surfaces and cast in any shape. The robust nature of the sol-gel converts the assays into a liquid-less sensor material that is portable, durable, and flexible, with a longer storage life than films and liposomes. It also allows for recovery and reuse.

Other Conjugated Polymer Systems
The Berkeley Lab team has demonstrated direct and rapid detection of analytes using conjugated polymer systems based on materials other than polydiacetylene. These systems have different optical properties than those described above and are soluble polymers instead of membranes. These materials are highly adaptable and sensitive.

PUBLICATIONS:

Charych, D.H., Nagy, J.O., Spevak, W., Bednarski, M.D., "Direct Colorimetric Detection of a Receptor-Ligand Interaction by a Polymerized Bilayer Assembly," Science, 1993, 261, 585-588.

Charych et al., "A 'Litmus Test' for Molecular Recognition Using Artificial Membranes," Chemistry and Biology, 1996, 3, 113-120.

PATENTS:

Polymeric Assay Film for Direct Colorimetric Detection. U.S. Patent #6,001,556 (IB-965B)
Polymeric Assay Film for Direct Colorimetric Detection. U.S. Patent #6,395,561 (IB-965C)
Polymeric Assemblies for Sensitive Colorimetric Assays. U.S. Patent #6,103,217 (IB-1062D)
Three-dimensional Colorimetric Assay Assemblies. U.S. Patent #6,080,423 (IB-1062F)
Doped Colorimetric Assay Liposomes. U.S. Patent #6,183,772 (IB-1131)
Sol-gel Matrices for Direct Colorimetric Detection of Analytes. U.S. Patent #6,022,748 (JIB-1160)
Sol-gel Matrices for Direct Colorimetric Detection of Analytes. U.S. Patent #6,485,987 (JIB-1160A)
Direct Colorimetric Detection of Biocatalysts. U.S. Patent #6,468,759 (IB-1236)
Methods for Using Redox Liposome Biosensors. U.S. Patent #6,387,614 (IB-1526)
Colorimetric Glycopolythiophene Biosensors. U.S. Patent #6,660,484 (IB-1578)

REFERENCE NUMBER: IB-965

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