Patent Issued for Sensor and Method for Detection of a Target Substance

By a News Reporter-Staff News Editor at Life Science Weekly — The Regents of the University of California (Oakland, CA) has been issued patent number 8765373, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also The Regents of the University of California).
The patent’s inventor is Majda, Marcin (Berkeley, CA).
This patent was filed on May 23, 2011 and was published online on July 1, 2014.
From the background information supplied by the inventors, news correspondents obtained the following quote: “The modern concept of biological sensors evolved considerably over the forty years since it was first demonstrated that enzymes could be immobilized at a surface of an electrochemical detector. Demands to reduce the sample volume, the cost and the time of analysis, and to increase sensitivity and selectivity have been most pressing in biological and biomedical sciences. This has fueled development of micro-analytical devices and bio-sensors with a wide range of applications in the clinical and defense settings, in gene and forensic analysis, in environmental monitoring, food safety and many other settings. While selectivity of biological sensors always derives from the unique molecular recognition interactions, such as antibody-antigen binding or complimentary deoxyribonucleic acid (DNA) hybridization, transduction and amplification of these events into analytically useful signal is often a major challenge.
“Interest in detecting DNA in a sequence-specific manner has grown steadily in recent years. The ability to rapidly and inexpensively detect DNA of specific sequences may allow more efficient pathogen, point mutation and gene detection. Multiple approaches of detecting DNA in a sequence-specific fashion have been explored, including optical (for example, chemiluminescence fluorescence, Raman spectroscopic and surface plasmon resonance), electronic as well as numerous electrochemical methods. Historically, fluorescence methods have been the most sensitive. However, advances in the electrochemical detection of DNA are becoming competitive in terms of sensitivity.
“Detection of pathogenic species in water is also an important and challenging problem. Several examples reporting direct response sensor devices sensitive to bacteria, viruses and bacterial toxins exist. These include, for example, colorimetric sensors designed to detect influenza virus and E. Coli and an electrochemical sensor responding to E. Coli enterotoxin.
“These technologies, however, have certain disadvantages. It is therefore desirable to provide improved methods and apparatus for electrochemical sensing of a target substance. In one example, it is desirable to provide sensors having microfabrication efficiencies that are highly accurate and yet inexpensive enough so that they are disposable.”
Supplementing the background information on this patent, NewsRx reporters also obtained the inventor’s summary information for this patent: “In one aspect, the invention features a sensor. The sensor comprises molecular tethers attached to a sensor surface such that at least some of a plurality of beads, as a result of a biological interaction between a target substance and the tethers, can at least one of be attached to the sensor surface by the tethers or released from the sensor surface by cleaving the tethers. The sensor further includes a measurement system configured and arranged to determine the population of beads at the sensor surface after the introduction of the analyte into the sensor.
“Various implementations of the invention may include one or more of the following features. A tether includes a hybrid double-stranded DNA molecule, an antibody, a modified antibody, a modified antigen or a peptide.
“In yet another aspect, the invention is directed to a sensor to determine if a target substance is present in an analyte. The sensor comprises a plurality of beads located in a channel and attached to a surface of the channel by a molecular tether. The tether can be selectively cleaved in the presence of a target substance to release at least some of the beads from the surface of the channel. The sensor further includes a measurement system configured and arranged to determine the population of beads in the channel after the introduction of the analyte into the channel.
“Various implementations of the invention may include one or more of the following features. The target substance is a target antigen and a molecular tether includes a modified antigen and an antibody with the modified antigen having a lower binding constant than the target antigen. The modified antigen has an approximately 2 orders of magnitude lower binding constant than the target antigen. The target substance is a target DNA and a molecular tether is a hybridized double-stranded DNA tether with one of the single-stranded DNA fragments of the double-stranded DNA tether being complementary to the target DNA. The hybridized double-stranded DNA tether includes first and second single-strand DNA fragments. The first single-strand DNA fragment is attached to a surface of the channel, and the sequence of the first single-strand DNA fragment is complementary to the target DNA. The second single-strand DNA fragment is attached to a surface of a bead. The measurement system may be a signal transduction system, a conductivity measurement system, a coulometric measurement system, a spectrometric measurement system, an optical measurement system, or an electrochemical counting system.
“In another aspect, the invention is directed to a sensor to detect a target antigen. The sensor comprises a plurality of beads attached to a sensor surface by a modified antigen and an antibody wherein the modified antigen has a lower binding constant than the target antigen.
“In still another aspect, the invention is directed to a sensor to detect a target antibody. The sensor comprises a plurality of beads attached to a sensor surface by a modified antibody and an antigen wherein the modified antibody has a lower binding constant than the target antibody.
“In another aspect, the invention is directed to a sensor to detect a target substance in an analyte. The sensor comprises a channel and a plurality of beads are located in the channel and attached to a surface of the channel by a molecular tether. The tether can be selectively cleaved in the presence of a target substance to release at least some of the beads from the surface of the channel. Measurement means are provided for determining the population of beads in the channel after the introduction of the analyte into the channel.
“In yet another aspect, the invention features a method of detecting a target substance. The method includes providing a number of molecular tethers at a channel surface of a sensor such that at least some of a plurality of beads, as a result of a biological interaction between a target substance and the tethers, can at least one of be attached to the channel surface by the tethers or released from the channel surface by cleaving the tethers. An analyte is introduced into the channel. Thereafter, the population of beads at the channel surface is determined to indicate a presence of the target substance in the analyte.
“Various implementations of the invention may include one or more of the following features. The tethers include a hybrid double-stranded DNA molecule, an antibody, a modified antibody, a modified antigen or a peptide. The target substance is a target DNA and a molecular tether is a hybridized double-stranded DNA tether with one of the single-stranded DNA fragments of the double-stranded tether being complementary to the target DNA. The hybridized double-stranded DNA tether includes first and second single-strand DNA fragments. The first single-strand DNA fragment is attached to a surface of the channel, and the sequence of the first single-strand DNA fragment is complementary to the target DNA. The second single-strand DNA fragment is attached to a surface of a bead.
“Other implementations of the invention may include one or more of the following features. The target substance is a target antigen and a molecular tether includes a modified antigen and an antibody with the modified antigen having a lower binding constant than the target antigen. The target substance is a target antibody and a molecular tether includes a modified antibody and an antigen with the modified antibody having a lower binding constant than the target antibody.
“The invention can include one or more of the following advantages. The sensor can detect a target substance such as DNA and a range of immunogens (antigens), a large group of macromolecules including cancer-specific proteins, toxins and numerous other pathogens. The sensor may be microfabricated and made small enough to be hand-held. The sensor may be disposable. The sensor functions without the use of reagents. The sensor may be part of an array. Each sensor of the array may respond to a specific DNA sequence. The sensor can simultaneously detect different target substances in sub-micron liter (uL) volumes of a solution at nano-Molar (nM) concentration levels.
“These and other features and advantages of the present invention will be presented in more detail in the following specification of the invention and the accompanying figures, which illustrate, by way of example, the principles of the invention.”
For the URL and additional information on this patent, see: Majda, Marcin. Sensor and Method for Detection of a Target Substance. U.S. Patent Number 8765373, filed May 23, 2011, and published online on July 1, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=\%2Fnetahtml\%2FPTO\%2Fsrchnum.htm&r=1&f=G&l=50&s1=8765373.PN.&OS=PN/8765373RS=PN/8765373
Keywords for this news article include: Antibodies, Chemistry, Viral DNA, Immunology, DNA Research, Blood Proteins, Electrochemical, Immunoglobulins, The Regents of the University of California.
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