News Column

"Biosensors" in Patent Application Approval Process

July 29, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- A patent application by the inventors Bhattacharyya, Dhiman (Arlington, MA); Gleason, Karen K. (Cambridge, MA), filed on July 13, 2012, was made available online on July 17, 2014, according to news reporting originating from Washington, D.C., by NewsRx correspondents (see also Patents).

This patent application has not been assigned to a company or institution.

The following quote was obtained by the news editors from the background information supplied by the inventors: "Food and waterborne pathogens cause a considerable amount of disease all over the world. The Centers for Disease Control and Prevention estimated that around 76 million cases of foodborne diseases occur in the USA, resulting in 325,000 hospitalizations and 5000 deaths occur each year. Billions of dollars are lost due to bacterial contamination in foods and a similar amount of money is spent for related health care costs. Some foodborne diseases are well recognized, but are considered emerging because they have recently become more common. Among the various pathogens that can cause food borne illness, Campylobacter, Salmonella, Listeria monocytogenes, and Escherichia coli O157:H7 have been generally found to be responsible for majority of food-borne outbreaks.

"Conventional food screening for detecting bio-threat risks and the toxins in the food supply can involve many steps, high labor and reagent costs, and be time consuming (e.g., minimum 2-3 days to obtain reliable information). Current biosensors can also suffer from user non-compliance because of the heavy weight of the sensor modules, and inflexibility of the sensor platforms for routine uses."

In addition to the background information obtained for this patent application, NewsRx journalists also obtained the inventors' summary information for this patent application: "Chemiresistive biosensors based on conductive polymers are described. The conductive polymers can be arranged on a high surface area substrate, such as a high surface area electro-spun polymer fiber mat. Such nanostructured fiber mats can be conformally coated by a conductive polymer, e.g., using oxidative chemical vapor deposition (oCVD). The oCVD polymer process is compatible with low-cost roll-to-roll manufacture. Functional groups in the conductive polymers can be further derivatized to immobilize analyte-specific binding reagents thus providing selectivity in detection of analytes. A wide variety of analytes can be detected by the biosensor, including pathogens.

"In one aspect, a chemiresistive biosensor is configured to detect an analyte, and includes a high specific surface area substrate conformally coated with a conductive polymer, and a binding reagent immobilized on the conductive polymer, wherein the binding reagent has a specific affinity for the analyte.

"The substrate can include an electro-spun polymer fiber mat. The substrate (e.g., the electro-spun polymer fiber mat) can have a BET surface area of at least 5 m.sup.2/g.

"The conductive polymer can be a copolymer including the monomer units -[A]-, -[B]-, and -[B*]-; where A, B, and B* are distinct monomers; a homopolymer of monomer A is a highly conductive polymer; monomer B includes a reactive functional group selected to form a covalent link to a binding reagent; and monomer B* is monomer B covalently linked to the binding reagent.

"The copolymer can have formula (I):

"-[A].sub.x-[B].sub.y-[B*].sub.z- (I)

"where x, y, and z are the mole fractions of monomer A, B, and B* in the copolymer, respectively; and 0y+z.

"Monomer A and monomer B, independently, each can be an optionally substituted aniline monomer, an optionally substituted pyrrole monomer, or an optionally substituted thiophene monomer. Monomer A can be an EDOT monomer. Monomer B can be a 3-TE monomer or a TAA monomer. The binding reagent can be a protein.

"In another aspect, a chemiresistive biosensor is configured to detect an analyte, and includes a high specific surface area substrate conformally coated with a conductive polymer; and a binding reagent immobilized on the conductive polymer, where the binding reagent has a specific affinity for the analyte; where the conductive polymer is a copolymer including the monomer units -[A]-, -[B]-, and -[B*]-; where A, B, and B* are distinct monomers; a homopolymer of monomer A is a highly conductive polymer; monomer B includes a reactive functional group selected to form a covalent link to a binding reagent; and monomer B* is monomer B covalently linked to the binding reagent.

"In another aspect, a sensor array includes a plurality of sensor elements, where each sensor element includes a chemiresistive biosensor, and where each sensor element is configured to detect a different analyte.

"In another aspect, a method of detecting an analyte includes contacting a sample suspected of containing the analyte with a chemiresistive biosensor which includes a high specific surface area substrate conformally coated with a conductive polymer; and a binding reagent immobilized on the conductive polymer; where the binding reagent has a specific affinity for the analyte.

"In another aspect, a method of detecting a plurality of analytes includes contacting a sample suspected of containing at least one of the plurality of analytes with a sensor array including a plurality of sensor elements, where each sensor element includes a chemiresistive biosensor, and where each sensor element is configured to detect a different analyte.

"In another aspect, a method of making a sensor configured to detect an analyte includes providing a high specific surface area substrate; coating a conductive polymer conformally on the high specific surface area substrate; and covalently linking a binding reagent to the conductive polymer, where the binding reagent has a specific affinity for the analyte.

"Coating can include contacting the substrate with a vapor including an oxidant, a first monomer A, and a distinct second monomer B; where a homopolymer of monomer A is a highly conductive polymer; and monomer B includes a reactive functional group selected to form a covalent link to a binding reagent.

"Covalently linking can include contacting the conductive polymer with the binding reagent and, optionally, a crosslinking reagent, thereby forming one or more covalent bonds covalently linking a binding reagent to the reactive functional group.

"Other aspects, embodiments, and features will become apparent from the following description, the drawings, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

"FIGS. 1A-1B are a schematic illustrations of chemiresistive biosensor devices.

"FIG. 1C schematically illustrates a chemiresistive biosensor array configured to detect more than one type of pathogens in a single device.

"FIG. 2 schematically illustrates a hand-held food pathogen detecting sensor. It has a sensor ribbon including a high surface area electro-spun fiber mat, a sensor clip (stick) to attach the ribbons with the working electrodes, and a sensor reader to monitor the output.

"FIG. 3 is a schematic presentation of the fabrication steps of a chemiresistive biosensor which includes an electro-spun polymer fiber mat.

"FIG. 4 illustrates the copolymerization of EDOT and 3TE using ferric chloride in an oCVD process. Chloride ions are present as dopant in the repeating units, but the number of dopants shown in FIG. 4 does not necessarily represent the actual dopant concentration.

"FIG. 5 shows FT-IR spectra of oCVD grown PEDOT, P3TE and P(EDOT-co-3TE) using iron (III) chloride as oxidant.

"FIGS. 6A-6C show scanning electron microscopic images of the (FIG. 6A) as prepared electro-spun nylon mat, (FIG. 6B) conductive copolymer coated mat, and (FIG. 6C) avidin immobilized to the conductive copolymer coated mat. Scale bar, 100 .mu.m.

"FIG. 7 illustrates covalent immobilization of protein molecules to the functional groups of the copolymer. R represents the rest of the copolymer chain.

"FIG. 8A shows X-ray photoelectron survey spectra of P(EDOT-co-3TE) copolymer, PMPI attached copolymer and avidin immobilized copolymer showing presence of O1s, C1s, S2s, S2p and C12p peaks. A step-wise increment in the atomic percent of nitrogen (N1s) was observed as highlighted in the box. FIGS. 8B-8C are laser scanning confocal microscope images of the fibers after covalent attachment of FITC-avidin (green fluorescence) to the fibers, and reaction of biotinylated red quantum dots to the FITC-avidin on the fibers, respectively. Scale bar, 50 .mu.m.

"FIG. 9 is a graph showing the response [Rp(%)] of a biosensor device to varying concentrations of biotin: 5 nM (rhombus), 50 nM (square), 500 nM (triangle) and 5 .mu.M (circles). The closed shapes represent experimental data; open shapes are the best fit data plotted with a solid line to show the trend. Error bars show the standard deviation of the experimental data.

"FIG. 10A is a comparison of the responses of devices made on an electro-spun mat (closed triangles) and a flat substrate (closed circles). The closed shapes represent experimental data; open shapes are the best fit data plotted with a solid line to show the trend. FIG. 10B is a comparative chart of maximum response [Rp(%) (max.)] and the response time for devices made on an electro-spun mat or on a flat substrate.

"FIG. 11 shows resistance of the as-deposited copolymer and avidin-linked copolymer."

URL and more information on this patent application, see: Bhattacharyya, Dhiman; Gleason, Karen K. Biosensors. Filed July 13, 2012 and posted July 17, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=2261&p=46&f=G&l=50&d=PG01&S1=20140710.PD.&OS=PD/20140710&RS=PD/20140710

Keywords for this news article include: Avidin, Bioengineering, Bionanotechnology, Biosensing, Biotechnology, Dietary Proteins, Glycoproteins, Nanobiotechnology, Nanotechnology, Ovalbumin, Patents.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Life Science Weekly


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