WO2006076507A2

WO2006076507A2 - Self-activated sensor

Info

Publication number: WO2006076507A2
Application number: PCT/US2006/001113
Authority: WO
Inventors: Harry L. Tuller; Min Yongki
Original assignee: Massachusetts Institute of Technology
Current assignee: Massachusetts Institute of Technology
Priority date: 2005-01-14
Filing date: 2006-01-13
Publication date: 2006-07-20
Anticipated expiration: 2007-07-14
Also published as: WO2006076507A3

Abstract

The present invention generally relates to self-activated sensors, including various systems and methods involving such sensors. In one aspect, 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. In another aspect, 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.

Description

SELF-ACTIVATED SENSOR

FEDERALLY SPONSORED RESEARCH

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.

FIELD OF INVENTION The present invention generally relates to self-activated sensors.

BACKGROUND 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. However, on the microscale (i.e., on scales generally less than about 1 ml) or smaller, producing separate sensor, microprocessor, and actuator elements for a given system is not trivial.

SUMMARY OF THE INVENTION

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.

In one aspect, the invention provides apparatus which can be a sensor in certain arrangements. In one embodiment apparatus is provided that includes an article comprising a piezoelectric material able to bind an analyte. In another embodiment 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.

In another embodiment, 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.

In another embodiment 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.

In another aspect 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.

In another set of embodiments, the invention includes an apparatus including a needle valve comprising a needle having a length of less than about 500 micrometers.

In another aspect, 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.

Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control. If two or more applications incorporated by reference include conflicting and/or inconsistent disclosure with respect to each other, then the later-filed application shall control. BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For the purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

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; and

Figs. 5A-5C illustrates an array of articles, according to certain embodiments of the invention.

DETAILED DESCRIPTION

The present invention generally relates to self-activated sensors, including various systems and methods involving such sensors.

In one aspect, 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.

In another aspect, 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.

Certain aspects of the present invention include the use of cantilevers. As used herein, 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. Thus, for example, in Fig. IA, 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). Thus, in reference to Fig. IA, 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. Although a cantilever is used to represent a functional component of the invention in some embodiments, it is to be understood that, wherever "cantilever" is used in the description of the invention, another component that is not a cantilever can be used. The cantilever may have any shape, depending on a particular application, as long as one end of the cantilever is a projecting structure. For example, 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). Similarly, 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) may be greater than the height and/or the width of the cantilever (i.e., the other two dimensions orthogonal to the length of the cantilever), and in some cases, 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. As used herein, 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). For example, 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. In certain instances, 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. In other instances, 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 .

One aspect of the present invention provides an article comprising an analyte- binding material and a piezoelectric material. In some cases, 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

(i.e., a substance to be measured) is able to bind, and typically is able to specifically bind (i.e., the analyte-binding material has a higher binding affinity for the analyte than for other species having similar, but not identical structures, to the 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. As one example, the analyte may be a gas, for example, H₂, CO₂, CO, N₂, O₂ , NO, NO₂, SO₂, a noble gas, O₃, or the like. Other examples of analytes include peptides, proteins, enzymes, nucleic acids, antibodies, viruses, hormones, ligands, a sugars, carbohydrates, etc. In one embodiment, the analyte-binding material and the analyte are binding partners. The term "binding partner, " as used herein, 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. The term "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). Thus, for example, in the case of a receptor/ligand binding pair 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. As used herein, "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. Thus, the analyte-binding material may be used to determine a concentration of an analyte within the detection region. As used herein, the term "determining" generally refers to the detection and/or measurement of a physical property of a species, for example, quantitatively or qualitatively.

According to certain embodiments of the invention, 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. Typically, 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. In certain instances, 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, according to other embodiments, include electronic, magnetic, and/or optical properties, for example, voltage, current, impedance, inductance, charge, emission intensity, emission wavelength, etc.

In certain cases, 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. In one embodiment, the covering material is an electrode, e.g., as further discussed below.

Articles of the invention also may, as noted above, include piezoelectric materials. As used herein, 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. Thus, upon application of an electric field, one or more dimensions of the piezoelectric material may increase or decrease. In certain instances, 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. In some cases, the degree to which the piezoelectric material alters its shape may be proportional to the intensity of the electric potential applied.

Examples of piezoelectric materials that are potentially suitable for use with the invention include certain materials containing oxoanions (i.e., containing salts where the anion comprises, or is, oxygen), for example, zinc oxide, lithium niobate, barium titanate, quartz, etc. In certain cases, the piezoelectric material has a perovskite crystal structure. Other examples of piezoelectric materials that are potentially suitable for use with the invention include berlinite (AlPO₄), gallium orthophosphate (GaPO₄), or certain materials having tungsten-bronze structures (e.g., BaTiO₃, KNbO₃, LiNbO₃, LiTaO₃, BiFeO₃, Na_xWO₃, Ba₂NaNb₅O₅, Pb₂KNb₅O₁₅, etc.).

The articles of the invention may also include one or more electrodes. As used herein, 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. Typically, the electrode is made out of a conductor, although semiconductor materials may be used in some cases, for example, silicon or GaAs. Examples of 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. Other suitable electrode materials can be determined by those of ordinary skill in the art. In some cases, 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," as used herein, 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.

According to one set of embodiments, 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). If 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. As 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. Thus, 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.

A schematic diagram of this process is shown in Fig. 2 as an illustrative example. In the embodiment shown in this figure, electrical circuit 10 includes a voltage source 15, an analyte-binding material 17 (depicted as a resistor R₁), and a piezoelectric material 18 (depicted as a resistor R₂). Electrical circuit 10 may also contain other electronic elements, such as electrodes, not shown here. R₁ and R₂ are positioned in series across voltage source 15. When an analyte 13 binds analyte-binding material 17, the resistance OfR₁ changes, which leads to a change in the net potential across R₁ and hence R₂, 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.

Specific, non-limiting examples of various embodiments of the invention are shown in Figs. 3A-3C. In the embodiment shown in Fig. 3A, 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. The other end of analyte-binding material 17, in turn, contacts one end of second electrode 32, also positioned on cantilevered portion 21. Second electrode 32 runs to the end of cantilevered portion 21. Positioned on top of second electrode 32, but not in direct contact with analyte-binding material 17, is piezoelectric material 18. 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

33, but is not directly connected to second electrode 32. 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. As used herein, "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.

In the arrangement shown in the example of Fig. 3B, a material having both piezoelectric and analyte-binding properties is used, according to another embodiment of the invention. In this figure, 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.

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 Yet another example of an arrangement is illustrated in Fig. 3C. In this embodiment, 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. 3 A and 3B. Instead, in this arrangement, 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. Positioned on first electrode 31 is piezoelectric material 18, also running along the full length of article 20. On top of piezoelectric material 18 is 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.

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.

As previously mentioned, in some embodiments, 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. For example, in one embodiment, 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. As a specific example, 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. As described above, in some cases, the article may have at least one dimension less than about 1 millimeter. Thus, 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.

One non-limiting example of such an actuation system is shown in Fig. 4. In Fig. 4, 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. Thus, 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.

In certain embodiments where an alteration in the shape of an article, for example, a distortion or displacement in at least a portion of the article, is to be determined, any suitable technique may be used to determine the alteration. For example, in one set of embodiments, an alteration in the shape of an article may be determined by microscopy, e.g., light microscopy, confocal microscopy, electron microscopy, etc.. In another set of embodiments, 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.). In yet another set of embodiments, 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.). Of course, in certain embodiments, no detection of any alteration in the shape of the article is required, for instance, in embodiments where 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. For example, 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. In this way, 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. As an example, referring now to Fig. 5 A, a substrate 50 is provided having a plurality of articles 51 thereon. Articles 51 may include those articles described above. Upon exposure of substrate 50 to a first analyte 53, at least some of articles 51 may experience a deflection or distortion, as is seen in Fig. 5B (for example article 54). Similarly, independently, exposure of substrate 50 to a second analyte 56 may cause at least some of articles 51 to experience a deflection or distortion, as is seen in Fig. 5C. Thus, by determining which articles 53 have been deflected or distorted, and/or to what extent (e.g., using the techniques described above), 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. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, 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. As one example, and as would be recognized by those of ordinary skill in the art, although 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.

AU definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms. The indefinite articles "a" and "an," as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean "at least one.

The phrase "and/or," as used herein in the specification and in the claims, should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the "and/or" clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, 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.

As used herein in the specification and in the claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when separating items in a list, "or" or "and/or" shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of or "exactly one of," or, when used in the claims, "consisting of," will refer to the inclusion of exactly one element of a number or list of elements. In general, the term "or" as used herein shall only be interpreted as indicating exclusive alternatives (i.e. "one or the other but not both") when preceded by terms of exclusivity, such as "either," "one of," "only one of," or "exactly one of." "Consisting essentially of, when used in the claims, shall have its ordinary meaning as used in the field of patent law. As used herein in the specification and in the claims, the phrase "at least one," in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase "at least one" refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B₅" or, equivalently "at least one of A and/or 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.

It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one act, the order of the acts of the method is not necessarily limited to the order in which the acts of the method are recited.

In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases "consisting of and "consisting essentially of shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

What is claimed is:

Claims

I. An apparatus, comprising: an article comprising a piezoelectric material able to bind an analyte.

2. An apparatus as in claim 1, further comprising means for determining displacement of a portion of the article upon binding of the analyte.

3. An apparatus as in claim 1, the apparatus further comprising a detector constructed and arranged to determine displacement of a portion of the article upon binding of the analyte.

4. An apparatus as in claim 1, wherein the article includes a cantilever.

5. An apparatus as in claim 4, wherein cantilever includes at least one portion having a thickness of less than about 500 micrometers.

6. An apparatus as in claim 5, wherein cantilever includes at least one portion having a thickness of less than about 300 micrometers.

7. An apparatus as in claim 6, wherein cantilever includes at least one portion having a thickness of less than about 100 micrometers.

8. An apparatus as in claim 7, wherein cantilever includes at least one portion having a thickness of less than about 30 micrometers.

9. An apparatus as in claim 8, wherein cantilever includes at least one portion having a thickness of less than about 10 micrometers.

10. An apparatus as in claim 9, wherein cantilever includes at least one portion having a thickness of less than about 3 micrometers.

I 1. An apparatus as in claim 10, wherein cantilever includes at least one portion having a thickness of less than about 1 micrometer.

12. An apparatus as in claim 4, wherein the cantilever has a maximum length, measured from a plane of attachment, of less than about 500 micrometers.

13. An apparatus as in claim 12, wherein the cantilever has a maximum length, measured from a point of attachment, of less than about 100 micrometers.

14. An apparatus as in claim 13, wherein the cantilever has a maximum length, measured from a point of attachment, of less than about 10 micrometers.

15. An apparatus as in claim 14, wherein the cantilever has a maximum length, measured from a point of attachment, of less than about 1 micrometer.

16. An apparatus as in claim 1, wherein the piezoelectric material comprises an oxoanion.

17. An apparatus as in claim 1, wherein the piezoelectric material comprises zinc oxide.

18. An apparatus as in claim 1 , wherein the piezoelectric material comprises lithium niobate.

19. An apparatus as in claim 1, wherein the piezoelectric material comprises barium titanate.

20. An apparatus as in claim 1, wherein the piezoelectric material comprises a perovskite crystal structure.

21. An apparatus as in claim 1, wherein the analyte is gaseous.

22. An apparatus as in claim 1, wherein the analyte includes water.

23. An apparatus as in claim 1, wherein the analyte includes CO.

24. An apparatus as in claim 1, wherein the analyte includes H₂.

25. An apparatus as in claim 1, wherein a portion of the piezoelectric material is unable to bind the analyte.

26. An apparatus as in claim 25, wherein the portion of the piezoelectric material unable to bind the analyte is positioned adjacent a covering material.

27. An apparatus as in claim 26, wherein at least a portion of the covering material is electrically conductive.

28. An apparatus as in claim 1, the article further comprising a first electrode in electrical communication with the piezoelectric material.

29. An apparatus as in claim 28, wherein the first electrode comprises a metal.

30. An apparatus as in claim 28, wherein the first electrode comprises a noble metal.

31. An apparatus as in claim 28, wherein the first electrode comprises platinum.

32. An apparatus as in claim 28, wherein the first electrode comprises aluminum.

33. An apparatus as in claim 28, the article further comprising a second electrode in electrical communication with the piezoelectric material.

34. An apparatus as in claim 33, wherein the first electrode and the second electrode are separated, at their closest approach, by no more than 500 micrometers.

35. An apparatus as in claim 34, wherein the first electrode and the second electrode are separated, at their closest approach, by no more than 100 micrometers.

36. An apparatus as in claim 33, wherein the article further comprises a third electrode not in physical contact with the first electrode nor the second electrode.

37. An apparatus as in claim 33, further comprising a voltage source in direct electrical communication with the first electrode and the second electrode.

38. An apparatus as in claim 1, further comprising a voltage source in electrical communication with the piezoelectric material.

39. An apparatus, comprising: 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.

40. An apparatus as in claim 39, further comprising means for determining displacement of a portion of the article upon binding of the analyte.

41. An apparatus as in claim 39, the apparatus further comprising a detector constructed and arranged to determine displacement of a portion of the article upon binding of the analyte.

42. An apparatus as in claim 39, wherein the article includes a cantilever.

43. An apparatus as in claim 42, wherein cantilever includes at least one portion having a thickness of less than about 500 micrometers.

44. An apparatus as in claim 39, wherein the piezoelectric material comprises an oxoanion.

45. An apparatus as in claim 39, wherein the piezoelectric material comprises zinc oxide.

46. An apparatus as in claim 39, wherein the analyte is gaseous.

47. An apparatus as in claim 39, the article further comprising a first electrode in electrical communication with the piezoelectric material.

48. An apparatus as in claim 47, the article further comprising a second electrode in electrical communication with the piezoelectric material.

49. An apparatus as in claim 48, wherein the first electrode and the second electrode are separated, at their closest approach, by no more than 500 micrometers.

50. An apparatus as in claim 48, wherein the article further comprises a third electrode not in physical contact with the first electrode nor the second electrode.

51. An apparatus as in claim 48, further comprising a voltage source in direct electrical communication with the first electrode and the second electrode.

52. An apparatus as in claim 39, further comprising a voltage source in electrical communication with the piezoelectric material.

53. A method, comprising : 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.

54. A method as in claim 53, wherein at least one article includes a cantilever.

55. A method as in claim 53, wherein the analyte is gaseous.

56. A method, comprising: providing an article including at least one portion having a thickness of less than about 500 micrometers, the article comprising a sensor and an actuator; applying an electrical potential across the sensor and the actuator; and applying a sample suspected of containing an analyte to the sensor, while maintaining the electrical potential across the sensor and the actuator at a substantially constant value.

57. A method as in claim 56, wherein the article includes a cantilever.

58. A method as in claim 56, wherein the piezoelectric material comprises an oxoanion.

59. A method as in claim 56, wherein the piezoelectric material comprises zinc oxide.

60. A method as in claim 56, wherein the analyte is gaseous.

61. An apparatus, comprising: a cantilever having a plane of attachment, the cantilever comprising a piezoelectric material and a material able to bind an analyte, wherein an 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.

62. An apparatus as in claim 61, further comprising means for determining displacement of a portion of the cantilever upon binding of the analyte.

63. An apparatus as in claim 61, the apparatus further comprising a detector constructed and arranged to determine displacement of a portion of the cantilever upon binding of the analyte.

64. An apparatus as in claim 61, wherein cantilever includes at least one portion having a thickness of less than about 500 micrometers.

65. An apparatus as in claim 61, wherein the piezoelectric material comprises an oxoanion.

66. An apparatus as in claim 61, wherein the piezoelectric material comprises zinc oxide.

67. An apparatus as in claim 61, wherein the analyte is gaseous.

68. An apparatus as in claim 61, the cantilever further comprising a first electrode in electrical communication with the piezoelectric material.

69. An apparatus as in claim 68, the cantilever further comprising a second electrode in electrical communication with the piezoelectric material.

70. An apparatus as in claim 69, wherein the first electrode and the second electrode are separated, at their closest approach, by no more than 500 micrometers.

71. An apparatus as in claim 69, wherein the cantilever further comprises a third electrode not in physical contact with the first electrode nor the second electrode.

72. An apparatus as in claim 69, further comprising a voltage source in direct electrical communication with the first electrode and the second electrode.

73. An apparatus as in claim 61, further comprising a voltage source in electrical communication with the piezoelectric material.

74. A method, comprising an act of: 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.

75. The method of claim 74, further comprising determining displacement of at least a portion of the piezoelectric material upon binding of the analyte.

76. A method as in claim 74, wherein the piezoelectric material comprises an oxoanion.

77. A method as in claim 74, wherein the piezoelectric material comprises zinc oxide.

78. A method as in claim 74, wherein the analyte is gaseous.

79. An apparatus, comprising: 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 comprising a voltage source in electronic communication with the first electrode and the second electrode.

80. An apparatus as in claim 79, wherein the first electrode comprises a metal.

81. An apparatus as in claim 79, wherein the second electrode comprises a metal.

82. An apparatus as in claim 79, wherein the piezoelectric material comprises an oxoanion.

83. An apparatus as in claim 79, wherein the piezoelectric material comprises zinc oxide.

84. An apparatus as in claim 79, wherein the piezoelectric material is directly coupled to the analyte-binding material.

85. An apparatus as in claim 79, further comprising an electrode coupled between the piezoelectric material and the analyte-binding material.

86. An apparatus, comprising: a sensor able to determine an analyte concentration in a detection region adjacent the sensor; and means for controlling the analyte concentration in the detection region, wherein the sensor is operatively linked, without a processor, to the means for controlling the analyte concentration.

87. An apparatus as in claim 86, wherein the sensor includes a cantilever.

88. An apparatus as in claim 87, wherein cantilever includes at least one portion having a thickness of less than about 500 micrometers.

89. An apparatus as in claim 86, wherein the analyte is gaseous.