WO2006076507A2 - Detecteur auto-active - Google Patents

Detecteur auto-active Download PDF

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Publication number
WO2006076507A2
WO2006076507A2 PCT/US2006/001113 US2006001113W WO2006076507A2 WO 2006076507 A2 WO2006076507 A2 WO 2006076507A2 US 2006001113 W US2006001113 W US 2006001113W WO 2006076507 A2 WO2006076507 A2 WO 2006076507A2
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WO
WIPO (PCT)
Prior art keywords
analyte
electrode
piezoelectric material
cantilever
article
Prior art date
Application number
PCT/US2006/001113
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English (en)
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WO2006076507A3 (fr
Inventor
Harry L. Tuller
Min Yongki
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Massachusetts Institute Of Technology
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Publication of WO2006076507A2 publication Critical patent/WO2006076507A2/fr
Publication of WO2006076507A3 publication Critical patent/WO2006076507A3/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/036—Analysing fluids by measuring frequency or resonance of acoustic waves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10J—PRODUCTION OF PRODUCER GAS, WATER-GAS, SYNTHESIS GAS FROM SOLID CARBONACEOUS MATERIAL, OR MIXTURES CONTAINING THESE GASES; CARBURETTING AIR OR OTHER GASES
    • C10J3/00—Production of combustible gases containing carbon monoxide from solid carbonaceous fuels
    • C10J3/72—Other features
    • C10J3/723—Controlling or regulating the gasification process
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/10—Apparatus specially adapted for use in combinatorial chemistry or with libraries for identifying library members
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00731—Saccharides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00734—Lipids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/0074—Biological products
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/025—Change of phase or condition
    • G01N2291/0256—Adsorption, desorption, surface mass change, e.g. on biosensors

Definitions

  • the present invention was sponsored by the National Science Foundation, Grant No. DMR9701699, OSP Project No. 6543200. The Government may have certain rights to the present invention.
  • the present invention generally relates to self-activated sensors.
  • Sensors, processors, and actuators are typically used to control physical features or characteristics in a system, and in some cases can be constructed to automatically do so without the need of human intervention.
  • Sensors are generally used to transform information from thermal, mechanical, chemical, optical, magnetic, or electrical sources into electrical signals compatible with microprocessors.
  • a microprocessor in turn, can processes the information and calculate an appropriate response.
  • the microprocessor can then direct an actuator to perform the specified response. For example, if the "actuator is a valve, and the microprocessor may direct the actuator to open or close the valve, or adjust its position.
  • the microscale i.e., on scales generally less than about 1 ml
  • producing separate sensor, microprocessor, and actuator elements for a given system is not trivial.
  • the present invention generally relates to self-activated sensors, including various systems and methods involving such sensors.
  • the subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles.
  • the invention provides apparatus which can be a sensor in certain arrangements.
  • apparatus includes an article comprising a piezoelectric material able to bind an analyte.
  • apparatus of the invention comprises an article including at least one portion having a thickness of less than about 500 micrometers, the article comprising a piezoelectric material in electrical communication with a material able to bind an analyte.
  • apparatus of the invention comprises a cantilever having a plane of attachment, the cantilever comprising a piezoelectric material and a material able to bind an analyte.
  • the average distance between the piezoelectric material and the plane of attachment is different from an average distance between the material able to bind the analyte and the plane of attachment, in this apparatus.
  • apparatus of the invention comprises an electrical circuit comprising, in series, a first electrode, a piezoelectric material including at least one portion having a thickness of less than about 500 micrometers, an analyte-binding material, and a second electrode.
  • the electrical circuit further comprises a voltage source in electronic communication with the first electrode and the second electrode.
  • the invention provides a series of methods.
  • One method of the invention comprises applying a sample suspected of containing an analyte to a plurality of articles and, thereafter, determining an amount of displacement of at least a portion of at least one article.
  • Another method of the invention comprises providing an article including at least one portion having a thickness of less than about 500 micrometers, where the article comprises a sensor and an actuator. An electrical potential is applied across the sensor and the actuator, and a sample suspected of containing an analyte is applied to the sensor, while electrical potential is maintained across the sensor and the actuator at a substantially constant value.
  • Another method of the invention comprises altering electrical resistance of at least a first portion of a piezoelectric material by causing an analyte to bind the first portion, wherein at least one dimension of a second portion of the piezoelectric material is altered upon binding of the analyte to the first portion.
  • the invention includes an apparatus including a needle valve comprising a needle having a length of less than about 500 micrometers.
  • the present invention is directed to a method of making one or more of the embodiments described herein, for example, a sensor comprising a piezoelectric material. In yet another aspect, the present invention is directed to a method of using one or more of the embodiments described herein, for example, a sensor comprising a piezoelectric material. In still another aspect, the present invention is directed to a method of promoting one or more of the embodiments described herein, for example, a sensor comprising a piezoelectric material.
  • Figs. 1 A-IB illustrate certain cantilever structures, according to various embodiments of the invention
  • Fig. 2 illustrates a circuit useful in certain embodiments of the invention
  • Figs. 3A-3C illustrates various embodiments of the invention
  • Fig. 4 illustrates a needle valve controlled by a piezoelectric material, in accordance with another embodiment of the invention.
  • Figs. 5A-5C illustrates an array of articles, according to certain embodiments of the invention.
  • the present invention generally relates to self-activated sensors, including various systems and methods involving such sensors.
  • the invention includes an article, for example, a cantilever, comprising a piezoelectric material that can bind an analyte, and/or is associated with an analyte-binding material.
  • a potential is placed across the piezoelectric material such that, upon binding of the analyte to the piezoelectric material and/or the analyte-binding material, the potential drop across the piezoelectric material is altered (for example, due to a change in resistivity in one of the materials), causing a displacement to occur in at least a portion of the article, which can be determined in some fashion. Electrical circuits involving such materials are also included.
  • the invention includes a control system, lacking a processor, that can determine the concentration of an analyte in some fashion and produce an appropriate response.
  • a “cantilever” is a projecting structure that is "fixed” or immobilized only at one end (although other structures may be used to temporarily support the cantilever elsewhere, for example, post 8 in Fig. IB, to which cantilever 5 has not been fixed).
  • the fixed end of the cantilever is referred to as the "point of attachment” or "region of attachment” although those of ordinary skill in the art will recognize that, at the fixed end of the cantilever, usually a region of the cantilever, rather than a single, 1- dimensional point, is fixed to a supporting structure.
  • cantilever 5 is supported on a support 3 at a region of attachment 4.
  • the "plane of attachment,” as used herein, is that portion of the region of attachment closest to the part of the cantilever that projects away from the support (i.e., that part of the cantilever that is not fixed).
  • the plane of attachment of cantilever 5 is indicated as plane 2.
  • the plane of attachment is not necessarily 2-dimensional. For instance, depending on the shape of the support, the plane of attachment may be curved, as shown in Fig. IB with plane of attachment 2.
  • the cantilever may have any shape, depending on a particular application, as long as one end of the cantilever is a projecting structure.
  • the cantilever may have a generally rectangular shape (e.g., Fig. IA), a square shape, a disc shape, or an irregular shape (e.g., Fig. IB).
  • the support that the cantilever has been fixed to at one end does not necessarily have to be linear (e.g., curved support 3 in Fig. IB).
  • the "length" of the cantilever i.e., the longest dimension of the cantilever
  • the height and/or the width of the cantilever i.e., the other two dimensions orthogonal to the length of the cantilever
  • the length of the cantilever may be at least about three times, at least about five times, at least about seven times, at least about ten times, or at least about fifteen times or more the maximum of the height and/or the width of the cantilever.
  • the cantilever may be a microcantilever in some cases.
  • a "microcantilever” is a cantilever having at least one dimension that is less than about 1 millimeter (i.e., having a dimension that is on the order of nanometers or less).
  • the cantilever (or other component of the invention) may have at least one portion having a thickness of less than about 1 millimeter, less than about 750 micrometers, less than about 500 micrometers, less than about 300 micrometers, less than about 100 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 3 micrometers, or less than about 1 micrometer or less.
  • two of the dimensions of the component may be less than about 1 millimeter, less than about 750 micrometers, less than about 500 micrometers, less than about 300 micrometers, less than about 100 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 3 micrometers, or less than about 1 micrometer or less. That is, in this embodiment, at least one cross-section of the component, two perpendicular lines can be drawn through the cross-section terminating at the boundary of the component, each of which does not exceed 1 millimeter or other dimensions noted above.
  • all of the dimensions of the component are less than about 1 millimeter or other dimensions noted above (that is, three perpendicular lines can be drawn through the component at some point, each terminating at the boundary of the component, each of which does not exeed 1 millimeter or other dimensions noted above .
  • an article comprising an analyte- binding material and a piezoelectric material.
  • the article may be a cantilever or a microcantilever, as discussed above.
  • the analyte-binding material itself may also be the piezoelectric material, in certain instances.
  • a potential is placed across the analyte-binding material and the piezoelectric material such that, when an analyte binds the analyte-binding material, the piezoelectric material causes a displacement to occur in at least a portion of the article.
  • An "analyte-binding material,” is used herein, is a material to which an analyte
  • the analyte-binding material may intrinsically be a material able to bind specific analytes, or the analyte-binding material may be a material treated or coated in a fashion that allows the material to specifically bind certain analytes, for example, through the use of the certain chemical reactions, self-assembled monolayers, various proteins or enzymes, or the like.
  • the analyte may be a gas, for example, H 2 , CO 2 , CO, N 2 , O 2 , NO, NO 2 , SO 2 , a noble gas, O 3 , or the like.
  • Other examples of analytes include peptides, proteins, enzymes, nucleic acids, antibodies, viruses, hormones, ligands, a sugars, carbohydrates, etc.
  • the analyte-binding material and the analyte are binding partners.
  • binding partner refers to a molecule that can undergo binding with a particular analyte, or “binding partner” thereof, and includes specific, semi-specific, and non-specific binding partners as known to those of ordinary skill in the art.
  • binding partner e.g., protein, nucleic acid, antibody, etc.
  • specifically binds when referring to a binding partner (e.g., protein, nucleic acid, antibody, etc.), refers to a reaction that is determinative of the presence and/or identity of one or other member of the binding pair in a mixture of heterogeneous molecules (e.g., proteins and other biologies).
  • the ligand would specifically and/or preferentially select its receptor from a complex mixture of molecules, or vice versa.
  • An enzyme would specifically bind to its substrate, a nucleic acid would specifically bind to its complement, an antibody would specifically bind to its antigen.
  • Other examples include, nucleic acids that specifically bind (hybridize) to their complement, antibodies specifically bind to their antigen, and the like.
  • the analyte-binding material may be able to bind an analyte present in a detection region surrounding the analyte-binding material.
  • a detection region is a spatial region surrounding the analyte-binding material such that the amount of binding of the analyte to the analyte-binding material is proportional (in some instances, directly proportional) to the concentration of analyte within the detection region.
  • the analyte-binding material may be used to determine a concentration of an analyte within the detection region.
  • the term “determining” generally refers to the detection and/or measurement of a physical property of a species, for example, quantitatively or qualitatively.
  • the analyte-binding material may be at least partially electrically conductive, i.e., the analyte-binding material allows an electrical current to pass through the material, such that the resistivity of the analyte- binding material can be determined.
  • the analyte-binding material has a resistivity that changes upon binding of an analyte to the analyte-binding material, and in some cases, the resistivity of the analyte-binding material may be proportional to the amount or degree of binding of analytes to the analyte-binding material.
  • the analyte-binding material may be electrically insulating (i.e., does not allow a current to pass through) when free of analyte, but becomes at least partially electrically conductive upon binding of an analyte to the material, or vice versa.
  • Other examples of properties that may be altered upon binding of an analyte to the analyte-binding material include electronic, magnetic, and/or optical properties, for example, voltage, current, impedance, inductance, charge, emission intensity, emission wavelength, etc.
  • a portion of the analyte-binding material may be covered with a covering material, i.e., a material that does not allow the analyte to pass through. Thus, regions of the analyte-binding material that are covered by the covering material cannot bind the analyte.
  • the covering material is an electrode, e.g., as further discussed below.
  • Articles of the invention also may, as noted above, include piezoelectric materials.
  • a piezoelectric material is given its ordinary definition as used in the art, i.e., a material that alters its configuration or shape, isotropically (equally in all dimensions) or aniostropcially (where some dimensions are preferred over others), upon the application of an electric potential.
  • one or more dimensions of the piezoelectric material may increase or decrease.
  • the changes in the shape of the piezoelectric material are reversible, i.e., the piezoelectric material returns to its original shape once the potential is removed; in other instances, however, changes to the shape of the piezoelectric material are irreversible.
  • the degree to which the piezoelectric material alters its shape may be proportional to the intensity of the electric potential applied.
  • AlPO 4 berlinite
  • GaPO 4 gallium orthophosphate
  • tungsten-bronze structures e.g., BaTiO 3 , KNbO 3 , LiNbO 3 , LiTaO 3 , BiFeO 3 , Na x WO 3 , Ba 2 NaNb 5 O 5 , Pb 2 KNb 5 O 15 , etc.
  • the articles of the invention may also include one or more electrodes.
  • an "electrode” is a material that has a lower resistivity than the analyte-binding material and is configured, relative to the analyte-binding material and other components of an overall device, to provide an electrical potential across the analyte-binding material which can lead to current flow across the material, and/or can otherwise define locations where electrical current and/or potential across the analyte-binding material can be determined and/or affected.
  • the electrode is made out of a conductor, although semiconductor materials may be used in some cases, for example, silicon or GaAs.
  • conductors include, but are not limited to, metals, for example, iron, aluminum, or noble metals such as silver, gold, copper, platinum, palladium, or the like.
  • suitable electrode materials can be determined by those of ordinary skill in the art.
  • the electrodes may be positioned on the article such that two or more of the electrodes are separated, at their closest approach, by no more than 500 micrometers, and in some cases, the electrodes are separated, at their closest approach, by less than about 300 micrometers, less than about 100 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 3 micrometers, or less than about 1 micrometer or less. Certain embodiments of the invention involve arrangements that doe not include a processor.
  • processor means an electronic or mechanical device that is configured to receive a signal from a sensor and to produce a signal to an actuator, and defines more than simply an electrical or mechanical connection between the sensor and the actuator.
  • Typical processors are electrical devices including transistors, capacitors, and/or other electrical components which, together, can receive a first signal and, on the basis of some distince popertty of the first signal (e.g. its existence, strength, duration, or the like) can generate a second, different signal.
  • a substantially constant or otherwise known electric potential is applied across a piezoelectric material and across an analyte- binding material in series with the piezoelectric material (other materials, e.g., electrodes, may also be in series as well).
  • the potential that forms across each material is proportional to the resistivities of the materials, and can be predicted and/or calculated based on known characteristics of the electric potential (e.g., if the potential is constant, or at least substantially constant).
  • the resistivity of the analyte-binding material changes (e.g., upon binding of an analyte to the analyte-binding material), then the relative ratios of the resistivities of the materials changes; thus, the potentials formed across each of the materials would also change.
  • the spatial dimensions of the piezoelectric material are a function of the potential experienced by the piezoelectric material, a change in the potential would thus lead to a change in the shape of the piezoelectric material.
  • binding of an analyte to the analyte-binding material causes the piezoelectric material to alter its shape, for example, in at least one spatial dimension. This alteration in shape may be used to produce a useful result, and/or determined in some fashion, e.g., as further described below.
  • electrical circuit 10 includes a voltage source 15, an analyte-binding material 17 (depicted as a resistor R 1 ), and a piezoelectric material 18 (depicted as a resistor R 2 ). Electrical circuit 10 may also contain other electronic elements, such as electrodes, not shown here. R 1 and R 2 are positioned in series across voltage source 15. When an analyte 13 binds analyte-binding material 17, the resistance OfR 1 changes, which leads to a change in the net potential across R 1 and hence R 2 , as the potential produced by voltage source 15 remains substantially constant or otherwise known during this process. Thus, piezoelectric material 18 experiences a change in potential, which causes piezoelectric material 18 to change its configuration or shape in some fashion. This alteration in shape can then be used to produce a useful result, and/or determined by detector 14.
  • article 20 includes base 29, including a cantilevered (unsupported) portion 21, and a fixed portion 26 that is attached to support 28.
  • Article 20 may be, but is not necessarily, a cantilever or a microcantilever.
  • Jointing fixed portion 26 and cantilevered portion 21 is a plane of attachment 22.
  • Article 20 also includes a first electrode 31, a second electrode 32, and a third electrode 33.
  • First electrode 31, positioned on fixed portion 26, is in electrical communication with (direct contact, as shown) with one end of analyte-binding material 17, positioned on cantilevered portion 21.
  • analyte-binding material 17 contacts one end of second electrode 32, also positioned on cantilevered portion 21.
  • Second electrode 32 runs to the end of cantilevered portion 21.
  • piezoelectric material 18 Positioned on top of second electrode 32, but not in direct contact with analyte-binding material 17, is piezoelectric material 18.
  • third electrode 33 Positioned on top of piezoelectric material 18 is third electrode 33, i.e., piezoelectric material 18 is "sandwiched" in between second electrode 32 and third electrode 33.
  • a voltage source 15 is directly connected to first electrode 31 and third electrode
  • Voltage source 15 in this example, is not part of article 20, but is connected to first electrode 31 and third electrode 33 through wires 11. In other embodiments, however, voltage source 15 may be part of article 20 and/or cantilevered portion 21. It should be noted that voltage source 15 is in electrical communication with electrode 32, as well as analyte-binding material 17 and piezoelectric material 18 (even though there is no direct connection) through first electrode 31 and third electrode 33. Thus, as can be seen in Fig. 3 A, first electrode 31, analyte-binding material 17, second electrode 32, piezoelectric material 18, and third electrode 33 are connected in series across voltage source 15.
  • electrical communication generally refers to communications which provides for the systematic transport of electric current from one location to another, directly, or through one or more intermediates (e.g., through wires, other electrical components, electrodes, etc.).
  • Binding of an analyte 13, present in a detection region surrounding analyte- binding material 17, to the material causes the material to experience a change in resistivity. Since analyte-binding material 17 and piezoelectric material 18 are in series across voltage source 15, which is substantially constant or otherwise known, there is a change in the potential across piezoelectric material 18, which causes piezoelectric material 18 to alter at least one spatial dimension. The change in at least one spatial dimension of piezoelectric material 18 may cause the cantilevered portion 21 of article 20 to experience a distortion or displacement at the cantilevered end.
  • This distortion or displacement, initially caused by the binding of analyte 13, can be detected and/or measured, as further described herein, and/or used to produce a useful result, for example, altering the concentration of analyte 13 surrounding article 20, for instance, by introducing a fluid to the region surrounding article 20, removing a fluid from the region surrounding article 20, altering the fiowrate of a fluid that passes through the region surrounding article 20, etc.
  • article 20 includes a base 29, including a cantilevered portion 21, and a fixed portion 26 that is attached to support 28, separated from cantilevered portion 21 by a plane of attachment 22.
  • a first electrode 31 is positioned on fixed portion 26, connected to a voltage source 15 by wires 11.
  • One end of first electrode 31 is in direct contact with material 34, which is both piezoelectric and able to bind to an analyte.
  • Material 34 covers second electrode 32, which is positioned on base 29 on the cantilevered portion 21, although second electrode 32 and first electrode 31 do not directly contact.
  • Third electrode 33 also positioned in the cantilevered portion 21, is positioned on top of material 34 such that material 34 is "sandwiched" in between second electrode 32 and third electrode 33. Third electrode 33 is also connected to voltage source 15 by wires 11. With this arrangement, shown in Fig. 3B, not all of material 34 is exposed to the environment surrounding article 20. Portions of material 34 are covered by third electrode 33, and thus those portions cannot bind analyte 13. Exposed portions of material 34, in this embodiment, include both ends of material 34, i.e., on fixed portion 26 and cantilevered portion 21, and those exposed portions of material 34 are able to bind to analyte 13.
  • article 20 Upon binding of analyte 13 to material 34, at least those portions of material 34 will experience a change in resistivity, leading to a change in the potential that occurs across other parts of material 34 due to voltage source 15.
  • the changes in potential that occur across material 34 causes changes in at least one spatial dimension of material 34, which may cause the cantilevered portion 21 of article 20 to experience a distortion or displacement at the cantilevered end.
  • This distortion or displacement, initially caused by the binding of analyte 13, can be detected and/or measured, and/or used to produce a useful result
  • Fig. 3C Yet another example of an arrangement is illustrated in Fig. 3C.
  • article 20 includes a cantilevered portion 21, and a fixed portion 26 attached to support 28, although there is no base material, unlike in Figs.
  • first electrode 31 which runs the full length of article 20 (including both cantilevered portion 21 and a fixed portion 26), is used as a base layer, on which other materials are positioned on.
  • piezoelectric material 18 Positioned on first electrode 31 is piezoelectric material 18, also running along the full length of article 20.
  • second electrode 32 which also runs along the full length of article 20, and on top of second electrode 32 is an insulating material 35. Insulating material 35 covers second electrode 32, except at the cantilevered end of the article, where a portion of second electrode 32 extends upwardly to connect with one end of analyte-binding material 17, which is positioned on top of insulating material 35, and runs along the full length of article 20.
  • Second electrode 32 also covers a portion of the far end of analyte-binding material 17, such that only the central portion of the analyte- binding material 17 is able to bind analyte 13.
  • the fixed end of analyte-binding material 17 is covered with third electrode 33, and is thus also unable to bind analyte 13.
  • Voltage source 15 connects to first electrode 31 and third electrode 33 through wires 11.
  • analyte-binding material 17 Upon binding of analyte 13 to analyte-binding material 17, analyte-binding material 17 experiences a change in resistivity which, in turn, causes a change in the potential across piezoelectric material 18.
  • the change in the potential across piezoelectric material 18 causes a change in at least one spatial dimension of piezoelectric material 18, which may thus cause distortion or displacement at the cantilevered end of article 20.
  • This distortion or displacement, initially caused by the binding of analyte 13, can be detected and/or measured, and/or used to produce a useful result.
  • the piezoelectric material itself may be part of an actuator or other device able to respond (e.g., to produce a useful result) in response to an analyte binding the analyte-binding material.
  • This response can be produced without the need for a processor, i.e., the article is a "self-activated sensor," or a sensor/actuator that can produce a response to an analyte without the need for a processor.
  • the article, including the piezoelectric material may be part of a valve, a trigger, a switch, a gate, or the like.
  • Binding of the analyte to the analyte-binding material causes the article to respond, for example, by opening (or changing the position of) the valve, switch, gate, etc., for example, introducing or removing a fluid, altering the flowrate of a fluid, etc.
  • the article may be part of a needle valve or a gate that proportionally opens or closes relative to the amount of analyte bound to the analyte-binding material.
  • the article may have at least one dimension less than about 1 millimeter.
  • an embodiment of the invention provides a needle valve having a needle having a length of less than 1 millimeter, and in some cases, the needle may have a length of less than about 750 micrometers, less than about 500 micrometers, less than about 300 micrometers, less than about 100 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 3 micrometers, or less than about 1 micrometer or less.
  • article 30 contains a piezoelectric material 18, positioned at a cantilevered end of the article. Directly contacting piezoelectric material 18 is analyte-binding material 17. Voltage source 15, which is part of article 30, is positioned using wires 11 such that piezoelectric material 18 and analyte-binding material 17 are in series across voltage source 15. Voltage source 15 produces a substantially constant or otherwise known electric potential. Attached to the cantilevered end of article 30 is a needle 42 that partially blocks opening 45 in substrate 47, as shown in Fig. 4.
  • Needle 42 partially (or totally) blocks opening 45 in substrate 47, inhibiting or preventing a fluid in channel 48 from exiting through opening 45.
  • the degree to which needle 42 allows a fluid to exit opening 45 is generally proportional to the degree at which needle 42 enters opening 45. This, in turn, is controlled by the amount of deflection or displacement produced by piezoelectric material 18 in response to binding of analyte 13 to analyte-binding material 17.
  • An increase in binding of analyte 13 to analyte-binding material 17 may cause more (or less, in some embodiments) movement of needle 42 into opening 45, and in some cases, may completely close off opening 45 such that a fluid is no longer able to pass through the opening.
  • control of fluid flow through opening 45 depends on the concentration of analyte 13 in the detection region surrounding analyte-binding material 17, and the fluid can be directly controlled, without the use of a processor.
  • an alteration in the shape of an article for example, a distortion or displacement in at least a portion of the article
  • any suitable technique may be used to determine the alteration.
  • an alteration in the shape of an article may be determined by microscopy, e.g., light microscopy, confocal microscopy, electron microscopy, etc..
  • alteration in the shape of the article may be determined by determining a change in an electrical property of the article, for example, by determining a change in electric field, a change in resistivity of at least a portion of the article (e.g., in the piezoelectric material and/or the analyte-binding material, etc.).
  • alteration in the shape of the article may be determined by determining a change in the physical properties of a fluid surrounding the articles (e.g., a change in fluid flow, concentration of a species, etc.).
  • the article is used as part of a self- activated sensor, as previously discussed.
  • Another aspect of the present invention provides a plurality of articles (for example, arranged in an array), where some or all of the articles are each able to independently determine one or more species, for example, using techniques such as those previously described.
  • the array may contain any number of articles, for example, 2, 3, 4, 5, 10, 15, 20, 25, 30, 50, 75, 100, 125, 150, 200, 250, 300, 400, 500, 750, 1,000, 2,000, 3,000, 4,000, 5,000, 7,500, 10,000, 100,000, or more articles may be present within the array.
  • the articles may be able to detect the same species and/or different species. For example, one or more articles may be able to determine a first species, while one or more other articles may be able to determine a second species, etc.
  • the specific species to be determined depends on the particular application, and includes those described above.
  • Species may be determined by measuring displacement of some or all of the articles in response to exposure to a sample suspected of containing the species.
  • a chemical, biological or biochemical sample suspected of containing one or more species may cause one set of articles (which may be able to bind the same or different analytes, and/or different portions of the analytes) to be deflected and/or displaced, while a second set of articles is not deflected or displaced, and/or is deflected and/or displaced to a different extent than the first set of articles.
  • complex analytes, and/or mixtures of analytes may be determined by an array of articles, each of which is able to detect a different characteristic of the one or more species.
  • a substrate 50 having a plurality of articles 51 thereon.
  • Articles 51 may include those articles described above.
  • Fig. 5B for example article 54
  • a second analyte 56 may cause at least some of articles 51 to experience a deflection or distortion, as is seen in Fig. 5C.
  • the analytes present in a given sample can be determined, using the plurality of articles. While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention.
  • any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present invention.
  • many components described herein are described and/or shown in various figures as being in direct connection to other components, many or all of these direct connections can be substituted by other connections, placing those components in electrical communication with each other via one or more intermediary components or connectors.
  • Those or ordinary skill can easily arrange various components relative to each other in a manner different than the manner shown in various figures and described herein, while achieving the benefit of and practicing within the scope of the claims of the present invention.
  • a reference to "A and/or B", when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.
  • At least one of A and B can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

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Abstract

La présente invention concerne des détecteurs auto-activés, y compris, divers systèmes et procédés impliquant de tels détecteurs. Dans un aspect, l'invention a pour objet un article, par exemple, un cantilever comprenant une matière piézo-électrique qui peut se lier à un analyte et/ou qui est associée à une matière se liant à un analyte. Un potentiel est placé à travers la matière piézo-électrique, de telle façon que, suite à la liaison de l'analyte à la matière piézo-électrique et/ou à la matière se liant à l'analyte, une baisse de potentiel à travers la matière piézo-électrique est altérée (par exemple, en raison d'un changement de résistivité dans une des matières), ce qui provoque un déplacement dans au moins une partie de l'article qui peut être déterminé d'une certaine façon. Ladite invention a aussi trait à des circuits électriques impliquant de telles matières. Dans un autre aspect, cette invention concerne un système de contrôle, exempt de processeur, qui peut déterminer la concentration d'un analyte d'une certaine manière et produire une réponse appropriée.
PCT/US2006/001113 2005-01-14 2006-01-13 Detecteur auto-active WO2006076507A2 (fr)

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US60/643,852 2005-01-14

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9823209B2 (en) 2010-10-05 2017-11-21 Anpac Bio-Medical Science Co., Ltd. Micro-devices for disease detection
US11085923B2 (en) 2011-03-24 2021-08-10 Anpac Bio-Medical Science Co., Ltd Micro-devices for disease detection

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US5445008A (en) * 1994-03-24 1995-08-29 Martin Marietta Energy Systems, Inc. Microbar sensor
US5658732A (en) * 1989-10-04 1997-08-19 E. I. Du Pont De Nemours And Company Assay method for biological target complexes on the surface of a biosensor
WO1998050773A2 (fr) * 1997-05-08 1998-11-12 University Of Minnesota Biocapteur en porte-a-faux
US6016686A (en) * 1998-03-16 2000-01-25 Lockheed Martin Energy Research Corporation Micromechanical potentiometric sensors

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US5658732A (en) * 1989-10-04 1997-08-19 E. I. Du Pont De Nemours And Company Assay method for biological target complexes on the surface of a biosensor
US5445008A (en) * 1994-03-24 1995-08-29 Martin Marietta Energy Systems, Inc. Microbar sensor
WO1998050773A2 (fr) * 1997-05-08 1998-11-12 University Of Minnesota Biocapteur en porte-a-faux
US6016686A (en) * 1998-03-16 2000-01-25 Lockheed Martin Energy Research Corporation Micromechanical potentiometric sensors

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9823209B2 (en) 2010-10-05 2017-11-21 Anpac Bio-Medical Science Co., Ltd. Micro-devices for disease detection
US10690613B2 (en) 2010-10-05 2020-06-23 Anpac Bio-Medical Science Co., Ltd. Micro-devices for disease detection
US11275048B2 (en) 2010-10-05 2022-03-15 Anpac Bio-Medical Science Co., Ltd. Micro-devices for disease detection
US11085923B2 (en) 2011-03-24 2021-08-10 Anpac Bio-Medical Science Co., Ltd Micro-devices for disease detection

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