Acoustic resonator device with controlled placement of functionalized material

Abstract

A micro-electro-mechanical system (MEMS) resonator device includes at least one functionalized material disposed on at least a central portion of a top side electrode, but less than the entire top side electrode. For an active region exhibiting maximum sensitivity at a center point and having reduced sensitivity along its periphery, omitting a functionalized material on at least one peripheral portion of the resonator active region prevents analytes from binding in the region of lowest sensitivity. A maximum length of the at least one functionalized material extends in a range of about 20% to about 95% of a length of the active region and a maximum width extends in a range of about 50% to 100% of a width of the active region. A method for manufacturing the MEMS resonator device is also provided.

Description

[0001] This application is a divisional application. The national application number of the parent application is: 201680088357.7 (international application number is PCT / US2016 / 058749), and the date of entry into the Chinese national phase is: February 11, 2019 (international application date is October 26, 2016). The name of the invention is: Acoustic resonator device with controlled placement of functionalized materials.

[0002] Statement of Related Application This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 373,668, filed August 11, 2016, the disclosure of which is incorporated herein by reference in its entirety. The subject matter disclosed herein is also related to the following three U.S. patent applications filed or to be filed on October 26, 2016: (1) U.S. Patent Application ___ entitled “Acoustic Resonator Apparatus and Method Providing Patterned Functionalized Regions,” (2) U.S. Patent Application ___ entitled “Acoustic Resonator Apparatus and Method for Functionalized Noble Metal Layers,” and (3) U.S. Patent Application ___ entitled “Acoustic Resonator Apparatus and Method for Fabrication Providing Hermeticity and Surface Functionalization,” the contents of which are hereby incorporated by reference as if fully set forth herein. Technical Field

[0003] The present disclosure relates to acoustic resonator devices, including acoustic wave sensors and fluidic devices suitable for biosensing or biochemical sensing applications. Background Art

[0004] A biosensor (or biological sensor) is an analytical device that includes a biological element and a transducer that converts the biological response into an electrical signal. Some biosensors involve a selective biochemical reaction between a specific binding material (e.g., an antibody, receptor, ligand, etc.) and a target substance (e.g., a molecule, protein, DNA, virus, bacteria, etc.), and the conversion of the product of this highly specific reaction into a measurable quantity by a transducer. Other sensors may utilize nonspecific binding materials that can bind to multiple types or classes of molecules or other moieties that may be present in a sample, such as those used in chemical sensing applications. The term "functionalized material" may be used herein to generally refer to both specific and nonspecific binding materials. The transduction methods used with biosensors can be based on a variety of principles, such as electrochemical, optical, electrical, and acoustic. Acoustic transduction offers many potential advantages, such as real-time, label-free, and low-cost operation, as well as exhibiting high sensitivity.

[0005] Acoustic wave devices utilize acoustic waves propagating through or on the surface of a piezoelectric material, whereby any change in the propagation path characteristics affects the wave's velocity and / or amplitude. The presence of a functionalized material on or above the active area of ​​the acoustic wave device allows analytes to bind to the functionalized material, thereby altering the mass vibrated by the acoustic wave and changing the wave's propagation characteristics (e.g., velocity, thereby changing the resonant frequency). Changes in velocity can be monitored by measuring the frequency, amplitude, or phase characteristics of the acoustic wave device and correlated to the physical quantity being measured.

[0006] In the case of piezoelectric crystal resonators, the acoustic waves can include bulk acoustic waves (BAWs) that propagate through the interior of the substrate, or surface acoustic waves (SAWs) that propagate on the surface of the substrate. SAW devices involve transducing acoustic waves (typically comprising two-dimensional Rayleigh waves) using interdigital transducers along the surface of the piezoelectric material, where the waves are confined to a penetration depth of approximately one wavelength.

[0007] BAW devices typically involve transducing acoustic waves using electrodes arranged on opposing top and bottom surfaces of a piezoelectric material. Three wave modes can propagate in a BAW device: one longitudinal mode (representing longitudinal waves, also known as compression / tension waves) and two shear modes (representing shear waves, also known as transverse waves). The longitudinal and shear modes identify vibrations in which the particle motion is parallel or perpendicular to the wave propagation direction, respectively. Longitudinal modes are characterized by compression and extension in the propagation direction, while shear modes consist of motion perpendicular to the propagation direction without local volume changes. Longitudinal and shear modes propagate at different velocities. In practice, these modes are not necessarily pure, as the particle vibration or polarization is neither purely parallel nor purely perpendicular to the propagation direction. The propagation characteristics of each mode depend on the material properties relative to the crystallographic axis orientation and the propagation direction. The ability to generate shear displacements facilitates the operation of acoustic wave devices with fluids, such as liquids, because shear waves do not transfer significant energy into the fluid.

[0008] Certain piezoelectric films, such as hexagonal piezoelectric materials including (but not limited to) aluminum nitride (AlN) and zinc oxide (ZnO), are capable of exciting both longitudinal and shear mode resonances. To excite waves including shear modes using a piezoelectric material layer positioned between electrodes, the polarization axis in the piezoelectric film must typically be nonperpendicular to the film plane (e.g., tilted relative to the film plane). In biosensing applications involving liquid media, the shear component of the resonator is utilized. In such applications, the piezoelectric material can be grown with a c-axis orientation that is nonperpendicular to the surface of the underlying substrate, enabling the BAW resonator structure to exhibit a primarily shear response when an AC signal is applied across the electrodes. Conversely, a piezoelectric material grown with a c-axis orientation that is perpendicular to the surface of the underlying substrate will exhibit a primarily longitudinal response when an AC signal is applied across its electrodes.

[0009] BAW devices are typically fabricated using microelectromechanical systems (MEMS) fabrication techniques due to the need to provide microscale features suitable for facilitating high-frequency operation. In the context of biosensors, functionalized materials (e.g., specific binding materials, also known as bioactive probes or reagents) can be deposited onto the sensor surface using a microarray spotting needle through microarray spotting (also known as microarray printing). Functionalized materials that provide nonspecific binding benefits (e.g., allowing the binding of multiple types or species of molecules) are also useful in certain contexts, such as chemical sensing. Unfortunately, the dimensional tolerances of microarray spotting are often greater than those allowed by MEMS fabrication techniques. Excessive amounts of specific binding material can reduce sensor response, for example by compromising the lower limit of detection. Separately, excess exposed nonspecific binding material can lead to undesirable analyte attachment during device use.

[0010] When the analyte is present at very low concentrations in a fluid sample, the sensitivity to changes in adsorbed mass is non-uniform across the surface of the active area of ​​a MEMS resonator-based biosensor, making it difficult to reliably achieve high sensitivity to changes in adsorbed mass. Furthermore, it can be difficult to provide large signal changes from small changes in adsorbed mass. This difficulty can be exacerbated when the analyte-containing fluid sample is supplied parallel to the upper surface of the biosensor's top-side electrode.

[0011] Therefore, there is a need for MEMS resonators employing functionalized materials, and fluidic devices and methods utilizing such resonators, that can reliably provide enhanced sensitivity to adsorbed masses and are suitable for operation in the presence of fluid (e.g., liquid) samples containing analytes for use in biosensing or biochemical sensing applications. Summary of the Invention

[0012] The present disclosure provides a microelectromechanical system (MEMS) resonator device disposed on a substrate and including at least one functionalized material disposed on at least a central portion of a top-side electrode, but less than the entire top-side electrode. For an active region exhibiting maximum sensitivity at a central point and decreasing sensitivity along its periphery, omitting the functionalized material from at least a peripheral portion of the resonator's active region prevents analyte binding in the region of lowest sensitivity. Reiterating, providing the functionalized material only on the central portion of the resonator's active region, where the sensitivity is greatest, provides a larger signal change due to a smaller change in the mass adsorbed by the functionalized material. This can be particularly beneficial when a MEMS resonator-based sensing device is used with fluid samples containing very low concentrations of analytes. Adjusting the size and configuration of the region containing the functionalized material relative to the active region can also enhance sensor response. For example, the maximum length of the at least one functionalized material can extend within a range of about 20% to about 95% of the length of the active region (or within a sub-range of about 30% to about 95%, or about 40% to about 90%, or about 50% to about 90%), and the maximum width can extend within a range of about 50% to 100% of the width of the active region (or within a sub-range of about 60% to about 100%, or about 70% to about 95%). When such a MEMS resonator device is incorporated into a fluidic device, the directionality of the region containing the functionalized material relative to the fluid flow containing the analyte can also be selected to enhance sensor response, which can be important when the analyte is present at very low concentrations.

[0013] In one aspect, the present disclosure relates to a microelectromechanical system (MEMS) resonator device comprising a substrate, a bulk acoustic wave resonator structure disposed on at least a portion of the substrate, and at least one functionalized material disposed on at least a central portion of a top-side electrode. The bulk acoustic wave resonator structure comprises a piezoelectric material, a top-side electrode disposed on a portion of the piezoelectric material, and a bottom-side electrode disposed between the piezoelectric material and the substrate, wherein a portion of the piezoelectric material is disposed between the top-side electrode and the bottom-side electrode to form an active area. The top-side electrode comprises an active area portion that overlaps the bottom-side electrode and coincides with the active area, the active area portion comprising an active area width, and the active area portion comprising an active area length that extends perpendicular to the active area width. The at least one functionalized material has a maximum length extending in the range of about 20% to about 95% (or in a sub-range of about 30% to about 95%, or about 40% to about 90%, or about 50% to 90%) of the length of the active area and a maximum width extending in the range of about 50% to 100% (or in a sub-range of about 60% to about 100%, or about 70% to about 95%) of the width of the active area.

[0014] In certain embodiments, the maximum width of at least one functionalized material exceeds its maximum length.

[0015] In some embodiments, the MEMS resonator device further comprises a self-assembled monolayer (SAM) disposed between the topside electrode and the at least one functionalized material. In some embodiments, the MEMS resonator device further comprises an interface layer (e.g., comprising an oxide layer, a nitride, or an oxynitride material) disposed between the topside electrode and the at least one functionalized material.

[0016] In some embodiments, the topside electrode comprises a non-noble metal, and the MEMS resonator device further comprises an airtight layer disposed between the interface layer and the topside electrode. If provided, the airtight layer preferably comprises a metal having a low water vapor transmission rate (e.g., not greater than 0.1 g / m 2 In some embodiments, the self-assembled monolayer is disposed between the interface layer and the at least one functionalized material. In some examples, the MEMS resonator device further comprises a blocking layer disposed over a portion of the piezoelectric material that is not aligned with the active region, wherein the blocking layer is configured to prevent binding of one or more substances.

[0017] In certain embodiments, at least one functionalized material comprises a specific binding material. In certain embodiments, at least one functionalized material comprises a non-specific binding material.

[0018] In certain embodiments, the piezoelectric material includes a c-axis having an orientation distribution that is significantly non-parallel to a normal to a face of the substrate.

[0019] In some embodiments, the MEMS resonator device further comprises at least one acoustic reflector element disposed between the substrate and the BAW resonator structure to form a securely mounted resonator structure. In other embodiments, the substrate defines a recess, and the MEMS resonator device further comprises a support layer disposed between the BAW resonator structure and the recess, wherein the active region is disposed over at least a portion of the support layer and over at least a portion of the recess, for example, forming a film bulk acoustic resonator (FBAR) structure.

[0020] In another aspect, the present disclosure relates to a sensor and / or fluidic device comprising a MEMS resonator device as disclosed herein. In one embodiment, the fluidic device comprising the MEMS resonator device comprises a fluidic channel encompassing an active area and arranged to direct a liquid flow to contact at least one functionalized material, wherein the fluidic channel is arranged to direct the liquid flow from an inlet upstream of the active area to the active area in a direction substantially parallel to the length of the active area. In certain embodiments, the at least one functionalized material is arranged in a shape comprising a leading edge (which may be straight, curved, angled, serrated, or other suitable shape), wherein a center point of the leading edge is arranged between the inlet and a center point of the active area.

[0021] In another aspect, the present disclosure relates to a method for biological or chemical sensing comprising a fluidic device as disclosed herein. One method step comprises supplying a fluid containing a target substance into a fluidic channel of the fluidic device, wherein the supplying is configured to cause at least some of the target substance to bind to at least one functionalized material. Another method step comprises inducing bulk acoustic waves in an active region and sensing a change in at least one of a frequency characteristic, an amplitude characteristic, or a phase characteristic of a bulk acoustic wave resonator structure to indicate at least one of the presence or amount of the target substance bound to the at least one functionalized material.

[0022] In another aspect, the present disclosure relates to a method for fabricating a microelectromechanical system (MEMS) resonator device. One method step includes forming a bulk acoustic wave resonator structure including a piezoelectric material, a topside electrode disposed on a portion of the piezoelectric material, and a bottomside electrode disposed between the piezoelectric material and a substrate, wherein a portion of the piezoelectric material is disposed between the topside electrode and the bottomside electrode to form an active area, the topside electrode including an active area portion that overlaps the bottomside electrode and coincides with the active area, the active area portion including an active area width, and the active area portion including an active area length that extends perpendicular to the active area width. Another method step includes depositing at least one functionalized material arranged on at least a central portion of the top-side electrode, wherein the at least one functionalized material has a maximum length extending in the range of about 20% to about 95% (or in a sub-range of about 30% to about 95%, or about 40% to about 90%, or about 50% to about 90%) of the length of the active area and a maximum width extending in the range of about 50% to 100% (or in a sub-range of about 60% to about 100%, or about 70% to about 95%) of the width of the active area.

[0023] In certain embodiments, the aforementioned method further includes forming a self-assembled monolayer on at least a portion of the topside electrode prior to depositing the at least one functionalizing material, wherein the at least one functionalizing material is disposed on at least a portion of the self-assembled monolayer. In certain embodiments, forming the self-assembled monolayer on at least a portion of the topside electrode comprises a plurality of steps, including: (i) applying the self-assembled monolayer on the topside electrode; (ii) disposing a first mechanical mask on the self-assembled monolayer, wherein the first mechanical mask defines at least one first aperture through which at least a first portion of the self-assembled monolayer is exposed; and (iii) transmitting electromagnetic radiation having a peak wavelength in the range of approximately 150 nm to 400 nm through the at least one first aperture to interact with the at least one first portion of the self-assembled monolayer to facilitate removal of the at least one first portion of the self-assembled monolayer. In certain embodiments, a method further includes disposing a second mechanical mask on at least a portion of the BAW resonator structure including the active region, wherein the second mechanical mask defines at least one second aperture through which at least a second portion of the self-assembled monolayer is exposed; and applying a blocking layer to the at least second portion of the self-assembled monolayer through the at least one second aperture. Certain embodiments further comprise the step of forming at least one wall on a portion of the BAW resonator structure and defining a fluid channel overlying the active area, wherein the fluid channel is arranged to direct a flow of liquid from an inlet upstream of the active area toward the active area in a direction substantially parallel to a length of the active area, and the fluid channel is arranged to direct the flow of liquid to contact the at least one functionalized material.

[0024] In another aspect, any of the aforementioned aspects and / or various individual aspects and features described herein can be combined to obtain additional advantages. Unless otherwise indicated herein, any of the various features and elements disclosed herein can be combined with one or more other disclosed features and elements.

[0025] Those skilled in the art will understand the scope of the present disclosure and implement additional aspects thereof after reading the following detailed description of the preferred embodiments in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate several aspects of the disclosure and, together with the description, serve to explain the principles of the disclosure.

[0027] Figure 1A is a schematic side cross-sectional view of a fluid channel including an active area of ​​a BAW MEMS resonator structure covered with a functionalized material, showing a Gaussian sensitivity distribution superimposed on the active area, and showing streamlines of a fluid front advancing in a left-right direction in the fluid channel transverse to a normal to an upper surface of the active area; Figure 1B yes Figure 1Aa schematic side cross-sectional view of the fluid channel, active area, and fluid front, further depicting the distribution of analytes upstream and downstream of the active area, wherein the accumulation of analytes is close to the radial boundary of the active area upstream of the center point of the active area; Figure 1C yes Figure 1B Schematic side cross-section of the fluid channel, active area, fluid front, analyte distribution and analyte accumulation, wherein Figure 1A The Gaussian sensitivity distribution of is superimposed on the active area; Figure 2 is a schematic cross-sectional illustration of a portion of a bulk acoustic wave (BAW) MEMS resonator device that may be used with embodiments disclosed herein, including an active region having a piezoelectric material disposed between overlapping portions of a top-side electrode and a bottom-side electrode; Figure 3 is a schematic cross-sectional illustration of an upper portion of a BAW resonator device including a piezoelectric material and a top-side electrode covered with an airtight layer, an interface layer, a self-assembled monolayer, and a functionalized material (e.g., a specific binding material); Figure 4 is a schematic cross-sectional illustration of a portion of a fluidic device (e.g., a biochemical sensor device) comprising a fluidic channel bounded from below by a BAW resonator structure covered with a functionalizing material, laterally bounded by walls, and bounded from above by a cover layer defining a fluidic port, wherein the functionalizing material extends across and across the entire active area; Figures 5A-5E Provided in performing sequential manufacturing steps and in combination according to Figure 2 Schematic cross-sectional view of a portion of a fluidic device (e.g., a biochemical sensor device) following a BAW resonator structure; Figure 5F It is a combination Figures 5A-5E Schematic cross-sectional view of a portion of a fluidic device of an intermediate structure shown in , wherein less than the entire active area of ​​a BAW resonator structure is covered with a functionalized material according to one embodiment; Figure 5G yes Figure 5F a schematic cross-sectional view of a portion of a fluidic device after use thereof, showing an analyte bound to a functionalized material; Figure 6 is similar to Figure 5F and 5G Schematic cross-sectional view of another fluidic device of a device, wherein according to one embodiment, less than the entire active area of ​​the BAW resonator structure is covered with a functionalized material; Figure 7Ais a schematic top plan view of an active area of ​​a fluidic device incorporating a BAW resonator structure according to one embodiment, wherein a central portion of the active area is covered with functionalized material arranged in a symmetrical circular configuration and an annular peripheral portion of the active area is free of functionalized material; Figure 7B and 7C Provided separately Figure 7A Schematic cross-sectional side and front views of the active area and functionalized materials; Figure 8A is a schematic top plan view of an active area of ​​a fluidic device incorporating a BAW resonator structure, wherein a central portion of the active area is covered with a functionalized material, the functionalized material being arranged in an elliptical configuration having a width greater than a length, wherein a maximum width of the active area is greater than a maximum width of the functionalized material, and a peripheral portion of the active area is free of functionalized material, according to one embodiment; Figure 8B and 8C Provided separately Figure 8A Schematic cross-sectional side and front views of the active area and functionalized materials; Figure 9A is a schematic top plan view of an active area of ​​a fluidic device incorporating a BAW resonator structure, wherein a central portion of the active area is covered with a functionalized material, the functionalized material being arranged in an elongated elliptical configuration having a width greater than a length, wherein a maximum width of the active area is equal to a maximum width of the functionalized material, and crescent-shaped front and rear peripheral portions of the active area are free of functionalized material, according to one embodiment; Figure 9B and 9C Provided separately Figure 9A Schematic cross-sectional side and front views of the active area and functionalized materials; Figure 10 is a schematic side cross-sectional view of an active region of a BAW resonator structure with a window-defining mechanical mask disposed over the active region to allow a precursor material for a self-assembled monolayer to be deposited through the window onto a portion of the active region; Figure 11 is a schematic side cross-sectional view of an active area of ​​a BAW resonator structure covered with a patterned photoresist layer to allow a precursor material for a self-assembled monolayer to be deposited on a portion of the active area through a window in the photoresist layer; Figure 12A is a schematic side cross-sectional view of an active region of a BAW resonator structure, the active region covered with an organosilane-based self-assembled monolayer (SAM), wherein a radiation blocking mechanical mask is disposed over the SAM, and wherein an electromagnetic radiation source is positioned to pass light through openings in the mask for selectively removing portions of the SAM; Figure 12B After removing the SAM along the periphery of the active area Figure 12A Schematic side cross-sectional view of the active region of a BAW resonator structure; Figure 13 is a photograph of a top plan view of a bulk acoustic wave MEMS resonator device suitable for receiving an airtight layer, an interface layer, a self-assembled monolayer, and functionalized (e.g., specific binding) materials as disclosed herein; Figure 14 is a perspective assembly view of a microfluidic device incorporating a substrate having a plurality of bulk acoustic wave MEMS resonator devices as disclosed herein, an intermediate layer defining channels containing active areas of the MEMS resonator devices, and a cover or protective layer; Figure 15 is a schematic cross-sectional view of a film bulk acoustic resonator (FBAR) structure that may be used in devices according to certain embodiments disclosed herein, wherein the FBAR structure includes a tilted c-axis hexagonal crystal structure piezoelectric material, a substrate defining a cavity covered by a support layer, and an active region aligned with the cavity, wherein a portion of the piezoelectric material is disposed between overlapping portions of a top-side electrode and a bottom-side electrode; Figure 16 is based on Figure 15 Schematic cross-sectional view of an FBAR structure after adding an airtight layer, an interface layer, a self-assembled monolayer, and a functionalizing material (eg, a specific binding material) to at least a portion of the FBAR structure. DETAILED DESCRIPTION

[0028] The embodiments set forth below represent the necessary information to enable those skilled in the art to practice the embodiments and illustrate the best mode for practicing the embodiments. Upon reading the following description in light of the accompanying drawings, those skilled in the art will understand the concepts of the present disclosure and will recognize the applications of these concepts not specifically set forth herein. It should be understood that these concepts and applications all fall within the scope of the present disclosure and the appended claims.

[0029] It should be understood that although the terms first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first element may be referred to as a second element, and similarly, a second element may be referred to as a first element without departing from the scope of this disclosure. As used herein, the term "and / or" includes any and all combinations of one or more of the related listed items.

[0030] It should also be understood that when an element is referred to as being “connected” or “coupled” to another element, it can be directly connected or coupled to the other element, or intervening elements may be present. In contrast, when an element is referred to as being “directly connected” or “directly coupled” to another element, there are no intervening elements.

[0031] It should be understood that although the terms "upper," "lower," "bottom," "middle," "center," "top," etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first element may be referred to as an "upper" element, and similarly, depending on the relative orientation of these elements, a second element may be referred to as an "upper" element without departing from the scope of this disclosure.

[0032] The terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the present disclosure. As used herein, the singular forms "a," "an," and "the" are also intended to include the plural forms, unless the context clearly indicates otherwise. It will be further understood that the terms "comprise," "comprising," and "include" when used herein specify the presence of the features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0033] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be further understood that the terms used herein should be interpreted as having a meaning consistent with their meaning in the context of this specification and the relevant art, and will not be interpreted in an idealized or overly formal sense unless explicitly defined as such herein.

[0034] The present disclosure provides a microelectromechanical system (MEMS) resonator device disposed on a substrate and including at least one functionalized material disposed on at least a central portion of a top-side electrode, but less than the entire top-side electrode. For an active region exhibiting maximum sensitivity at the center and decreasing sensitivity along its periphery, omitting the functionalized material from at least a peripheral portion of the resonator's active region prevents analyte binding in the region of lowest sensitivity. Adjusting the size and configuration of the region containing the functionalized material relative to the active region can also enhance sensor response. For example, the at least one functionalized material can have a maximum length within a range of about 20% to about 95% (or within a subrange of about 30% to about 95%, or about 40% to about 90%, or about 50% to about 90%) of the length of the active region and a maximum width within a range of about 50% to 100% (or within a subrange of about 60% to about 100%, or about 70% to about 95%) of the width of the active region.

[0035] Quartz microbalances are known to exhibit a frequency response that varies as a Gaussian function of distance from the center (i.e., the center exhibits the highest sensitivity to changes in mass, and sensitivity decreases away from the center). See, for example, S. Zhang et al., Applied Physics A 64, 545-552 (1997). Applicants have hypothesized that similar phenomena may apply to sensors based on bulk acoustic wave MEMS resonators and fluidic devices incorporating sensors for biosensing or biochemical sensing applications as disclosed herein. When the concentration of analyte in a sample is extremely low (e.g., in certain medical diagnostic applications), it may be highly advantageous to allow analyte binding only in the most sensitive regions of a resonator-based biochemical sensor device. Again, it may be highly advantageous to prevent analyte binding in insensitive or relatively insensitive regions (e.g., regions outside the sensor active area) and regions within the sensor active area that exhibit low sensitivity to changes in adsorbed mass.

[0036] Figures 1A-1C A schematic side cross-sectional view of a fluid channel 10 containing an active region 20 of a BAW MEMS resonator device is provided, wherein the active region 20 includes functionalized materials disposed thereon. The fluid channel 10 may be characterized as microfluidics. Figure 1A In FIG. 1 , a Gaussian sensitivity profile 22 is superimposed on an active area 20, illustrating a maximum sensitivity at a center point 18 of the active area 20 and a curvilinear decrease in sensitivity away from the center point 18 (e.g., exhibiting a minimum sensitivity at the peripheral edges (e.g., leading edge 16). Fluid channel 10 includes lower and upper boundaries 12A, 12B, which contain a leading edge of a fluid 14 under laminar flow conditions, such as those experienced in a microfluidic channel (also referred to as a microchannel). The leading edge of the fluid 14 can be represented as the fluid following parallel streamline paths 14A-14N, having a relatively low velocity near lower and upper boundaries 12A, 12B, and a relatively high velocity in the middle portion of the fluid channel 10 between boundaries 12A, 12B. As the leading edge of the fluid 14 flows through the active area 20, the portion of the fluid proximate lower streamline path 14A experiences interaction with the active area 20.

[0037] Although not in Figure 1A , but the fluid within the fluid channel 10 may include at least one analyte that undergoes interaction with the active region 20 . Figure 1B The fluid channel 10, the active area 20 and Figure 1A16. The front of the fluid 14 is shown, and the distribution of analytes 24 upstream and downstream of the leading edge 16 of the active area 20 is also shown. As the front of the fluid 14 flows through the active area 20, analytes 24 contained in the fluid near the lower boundary 12A may bind to the functionalized material of the active area 20. If the functionalized material is distributed throughout the active area 20, analytes 24 contained in the fluid near the lower streamline path 14A may bind to the first functionalized material it contacts, thereby forming an analyte accumulation 24A near the leading edge 16 of the active area 20. Unfortunately, the portion of the active area 20 near the leading edge 16 is significantly less sensitive to changes in adsorbed mass than the center point 18 of the active area, as shown in FIG. Figure 1C shown (which provides Figure 1B Same content, but Figure 1A The Gaussian sensitivity distribution 22 is superimposed on the active area 20).

[0038] Fluids in laminar flow tend to follow parallel streamline paths, so that the chaotic fluctuations in velocity that tend to homogenize fluids in turbulent flow are absent. Multiple fluids introduced into a standard microchannel do not typically mix with one another except by diffusion at common interfaces between the fluids, and this diffusion process is typically slow compared to fluid flow along the main axis of the microfluidic channel. The same principles that inhibit rapid mixing of fluids flowing under laminar flow conditions in a microfluidic channel also affect the distribution of analytes contained in one or more fluids flowing within a microfluidic channel. Fick's first law of diffusion states that flux moves from areas of high concentration to areas of low concentration. Second, the flux rate is proportional to the difference in concentration gradient.

[0039] refer to Figure 1B and 1C , the front of the fluid 14 containing the analyte 24 can be modeled as a moving "stack" of horizontal fluid layers (e.g., corresponding to streamline paths 14A-14N). Even assuming a constant analyte concentration in each layer of the stack forming the fluid volume upstream of the active area 20, after the fluid volume passes through the functionalized material covering the active area 20, the analyte 24 may bind to the functionalized material (e.g., Figure 1B and 1C24A in the fluid channel 10). However, due to slow diffusion in a direction perpendicular to the direction of fluid flow through the fluidic channel 10, and the need for analyte 24 to diffuse to the functionalized material overlying the active area 20 in order to bind, analyte 24 present in fluidic layers other than the lowest fluidic layer may not be available to bind to the functionalized material of the active area 20 within a reasonable period of time. Consequently, the concentration of analyte 24 may remain stratified within the fluidic channel 10 until diffusion occurs. Consequently, when analyte 24 present in the lowest fluidic layer of the leading edge of the fluid 14 binds to the functionalized material disposed along the leading edge 16 of the active area 20, an analyte accumulation 24A may form near the leading edge 16, but very little analyte binding may occur near the center point 18 of the active area 20. Given a Gaussian sensitivity profile 22 , the presence of analyte accumulation 24A at the leading edge 16 of the active area 20 and the absence of analyte binding to the functionalized material near the center 18 of the active area 20 , the combination of these two will result in a limited (low) aggregate response for the sensor comprising the active area 20 .

[0040] As previously discussed, adjusting the size and configuration of the region containing the functionalized material relative to the active region can enhance sensor response. For example, the at least one functionalized material can have a maximum length in the range of about 20% to about 95% of the length of the active region (or within a sub-range of about 30% to about 95%, or about 40% to about 90%, or about 50% to about 90%), and a maximum width in the range of about 50% to 100% of the width of the active region (or within a sub-range of about 60% to about 100%, or about 70% to about 95%). Methods for applying the at least one functionalized material over less than the entire active region can include, but are not limited to, one or more of the following: patterning the functionalized material over one or more regions of the active region using one or more mechanical masks or patterned photoresist layers; patterning an interfacial layer (disposed to underlie and receive the functionalized material) over one or more regions of the active region; or patterning a blocking material (disposed to prevent binding of the functionalized material and / or analyte) over one or more regions of the active region. By using these methods, functionalized materials can be applied and / or made available for analyte binding with higher dimensional tolerances than can be achieved by microarray spotting alone.

[0041] Before describing methods for applying at least one functionalizing material over less than the entire active area of ​​a resonator device, exemplary bulk acoustic wave MEMS resonator devices, associated layers for providing biochemical sensing benefits, and fluidic devices incorporating MEMS resonator devices will be introduced.

[0042] Preferred microelectromechanical system (MEMS) resonator devices according to certain embodiments include a substrate, a BAW resonator structure disposed on at least a portion of the substrate, and a functionalized material disposed on at least a portion of an active area of ​​the BAW resonator structure. Various layers may be disposed between the functionalized material and a topside electrode (which coincides with the active area of ​​the BAW resonator structure), such as a hermetic layer (e.g., to protect the topside electrode from corrosion in a liquid environment), an interface layer, and / or a self-assembled monolayer (SAM), wherein the interface layer and / or the SAM may be used to facilitate adhesion of at least one overlying material layer, ultimately including the functionalized material. In certain embodiments, the interface layer facilitates adhesion of the overlying SAM, and the SAM facilitates adhesion of the overlying functionalized material.

[0043] Figure 2 FIG2 is a schematic cross-sectional view of a portion of a bulk acoustic wave MEMS resonator device 30 that can be used with embodiments disclosed herein. The resonator device 30 includes a substrate 32 (typically silicon or another semiconductor material, for example), an acoustic reflector 34 disposed on the substrate 32, a piezoelectric material 42, and bottom and top electrodes 40 and 48. The bottom electrode 40 is disposed along a portion of a lower surface 44 of the piezoelectric material 42 (between the acoustic reflector 34 and the piezoelectric material 42), and the top electrode 48 is disposed along a portion of an upper surface 46 of the piezoelectric material 42. The region of the piezoelectric material 42 disposed between the overlapping portions of the top and bottom electrodes 48 and 40 is considered the active region 50 of the resonator device 30. The acoustic reflector 34 serves to reflect acoustic waves and thereby reduce or prevent their dissipation in the substrate 32. In some embodiments, the acoustic reflector 34 includes alternating thin layers 36, 38 of materials having different acoustic impedance values ​​(e.g., silicon oxycarbide [SiOC], silicon nitride [Si3N4], silicon dioxide [SiO2], aluminum nitride [AlN], tungsten [W], and molybdenum [Mo]) deposited on the substrate 32, optionally implemented as a quarter-wave Bragg reflector. In some embodiments, other types of acoustic reflectors may be used. The steps of forming the resonator device 30 may include depositing the acoustic reflector 34 on the substrate 32, followed by depositing the bottom-side electrode 40, then growing (e.g., by sputtering or other suitable methods) the piezoelectric material 42, followed by depositing the top-side electrode 48.

[0044] In certain embodiments, the piezoelectric material 42 comprises a hexagonal crystal structure piezoelectric material (e.g., aluminum nitride or zinc oxide) that includes a c-axis having an orientation distribution that is primarily non-parallel (and optionally non-perpendicular) to a plane normal to the substrate 32. Under appropriate conditions, the presence of a c-axis having an orientation distribution that is primarily non-parallel to the plane normal to the substrate enables the BAW resonator structure to be configured to exhibit a primarily shear response when an AC signal is applied across a distal electrode and its proximal electrode (e.g., as may be desired in the context of a BAW resonator structure providing sensing utility). Methods for forming a hexagonal crystal structure piezoelectric material that includes a c-axis having an orientation distribution that is primarily non-parallel to a plane normal to the substrate are disclosed in U.S. Patent Application No. 15 / 293,063, filed on October 13, 2016, which is incorporated herein by reference. Additional methods of forming piezoelectric materials having a tilted c-axis orientation are disclosed in US Pat. No. 4,640,756, issued Feb. 3, 1987, which is incorporated herein by reference.

[0045] Figure 2 The bulk acoustic wave MEMS resonator device 30 shown in FIG is free of any layers (eg, including functionalized materials) covering the active region 50, which would allow the resonator device 30 to be used as a biochemical sensor. Figure 2 At least a portion of the resonator device 30 shown in FIG, including the active region 50 , for example, can be covered with various layers, such as one or more of: an airtight layer, an interface layer, a self-assembled monolayer (SAM), and / or a layer of functionalized material (which may include a specific binding material or a non-specific binding material).

[0046] Figure 3 is a schematic cross-sectional view of an upper portion of a BAW resonator device including a piezoelectric material 42 and a top-side electrode 48 covered with a hermetic layer 52, an interface layer 54, a self-assembled monolayer (SAM) 56, and a layer of functionalized material (e.g., a specific binding material) 58. In certain embodiments, one or more blocking materials (not shown) may be applied during fabrication, for example, over portions of the interface layer to prevent localized attachment of one or more subsequently deposited layers, or (if applied over selected areas of the SAM or functionalized material) to prevent analyte capture in areas not covering the active area of ​​the BAW resonator device.

[0047] In some embodiments, photolithography can be used to facilitate patterning of interface materials or blocking materials on portions of the MEMS resonator device. Photolithography involves the use of light to transfer a geometric pattern from a photomask to a light-sensitive chemical photoresist on a substrate and is a process well known to those skilled in the art of semiconductor manufacturing. Typical steps employed in photolithography include wafer cleaning, photoresist coating (involving either positive or negative photoresists), mask alignment, and exposure and development. After defining features in the photoresist on the desired surface, the interface layer can be patterned by etching into one or more gaps in the photoresist layer, and the photoresist layer can then be removed (e.g., using a liquid photoresist stripper, ashing by applying an oxygen-containing plasma, or other removal process).

[0048] In certain embodiments, an interfacial layer (e.g., which may be disposed between a topside electrode and a SAM) comprises a hydroxylated oxide surface suitable for forming an organosilane SAM. A preferred interfacial layer material comprising a hydroxylated oxide surface is silicon dioxide (SiO2). Alternative materials that incorporate a hydroxylated oxide surface to form the interfacial layer include silicon dioxide [SiO2], titanium dioxide [TiO2], tantalum pentoxide [Ta2O5], hafnium oxide [HfO2], or aluminum oxide [Al2O3]. Other alternative materials comprising a hydroxylated oxide surface are known to those skilled in the art, and such alternatives are considered within the scope of the present disclosure.

[0049] In other embodiments, the interface layer (e.g., which may be disposed between the topside electrode and the SAM), or at least one electrode without an overlying interface layer, comprises gold or another noble metal (e.g., ruthenium, rhodium, palladium, osmium, iridium, platinum, or silver) that is suitable for receiving a thiol-based SAM that may be capped with a functionalizing material.

[0050] In certain embodiments incorporating electrode materials subject to corrosion, a gas barrier layer may be applied between the top-side electrode and the interface layer. When noble metals (e.g., gold, platinum, etc.) are used for the top-side electrode, a gas barrier layer may not be required. If provided, the gas barrier layer preferably comprises a metal having a low water vapor transmission rate (e.g., no greater than 0.1 g / m 2 After depositing the airtight layer and the interface layer, a SAM can be formed on the interface layer. In some embodiments, the SAM comprises an organosilane material. The airtight layer protects the reactive electrode material (e.g., aluminum or aluminum alloy) from corrosion in the corrosive liquid environment, and the interface layer promotes proper chemical bonding of the SAM.

[0051] In certain embodiments, the airtight layer and / or the interfacial layer may be applied by one or more deposition processes such as atomic layer deposition (ALD), chemical vapor deposition (CVD), or physical vapor deposition (PVD). Of these processes, ALD is preferred for depositing at least the airtight layer (and may also be preferred for depositing the interfacial layer) because it can provide an excellent conformal coating with good step coverage of device features, thereby providing a layer structure free of pinholes. Furthermore, ALD can form a uniform, thin layer that provides relatively little attenuation of acoustic vibrations, which would otherwise degrade device performance. Adequate coverage is important for the airtight layer (if present) to avoid corrosion of the underlying electrodes. If ALD is used to deposit the airtight layer, in certain embodiments, the airtight layer may comprise a thickness ranging from about 5 nm to about 100 nm, or from about 5 nm to about 50 nm, or from about 10 nm to about 25 nm. In certain embodiments, the airtight layer has a thickness of about 15 nm, or from about 12 nm to about 18 nm. In contrast, if another process such as chemical vapor deposition is used, the airtight layer may include a thickness in the range of about 80 nm to about 150 nm or greater, or in the range of about 80 nm to about 120 nm. Considering the two aforementioned processes, the airtight layer thickness may be in the range of about 5 nm to about 150 nm. If ALD is used for the deposition of the interfacial layer, the interfacial layer may include a thickness in the range of about 5 nm to about 15 nm. In certain embodiments, the interfacial layer may include a thickness of about 10 nm, or in the range of about 2 nm to about 20 nm, or about 5 nm to about 15 nm, or about 8 nm to about 12 nm. Other interfacial layer thickness ranges and / or deposition techniques besides ALD may be used in certain embodiments. In certain embodiments, the airtight layer and the interfacial layer may be applied sequentially in a vacuum environment to promote a high quality interface between the two layers.

[0052] If provided, the airtight layer may comprise an oxide, nitride, or oxynitride material that serves as a dielectric material and has a low water vapor transmission rate (e.g., no greater than 0.1 g / m2 / day). In certain embodiments, the airtight layer comprises at least one of aluminum oxide (Al2O3) or silicon nitride (SiN). In certain embodiments, the interface layer comprises at least one of SiO2, TiO2, or Ta2O5. In certain embodiments, multiple materials may be combined in a single airtight layer, and / or the airtight layer may comprise multiple sublayers of different materials. Preferably, the airtight layer is further selected to promote compatibility with the underlying reactive metal (e.g., aluminum or aluminum alloy) electrode structure of the acoustic resonator structure. Although aluminum or aluminum alloys are often used as electrode materials in BAW resonator structures, a variety of transition and post-transition metals may be used for such electrodes.

[0053] After deposition of the interfacial layer (optionally disposed on an underlying airtight layer), a SAM is preferably formed on the interfacial layer. SAMs are typically formed by exposing a solid surface to amphiphilic molecules possessing chemical groups that exhibit a strong affinity for the solid surface. When using an interfacial layer comprising a hydroxylated oxide surface, organosilane SAMs are particularly preferred for attachment to the hydroxylated oxide surface. Organosilane SAMs facilitate surface bonding via silicon-oxygen (Si-O) bonds. More specifically, organosilane molecules contain hydrolysis-sensitive groups and organic groups and are therefore useful for coupling inorganic materials to organic polymers. Organosilane SAMs can be formed by exposing the hydroxylated oxide surface to an organosilane material in the presence of trace amounts of water to form intermediate silanol groups. These groups then react with free hydroxyl groups on the hydroxylated surface to covalently anchor the organosilane. Examples of possible organosilane-based SAMs compatible with interfacial layers comprising hydroxylated oxide surfaces include 3-glycidyl ether propyl trimethoxy silane (GPTMS), 3-mercaptopropyl trimethoxy silane (MPTMS), 3-aminopropyl trimethoxy silane (APTMS), and octadecyl trimethoxy silane (OTMS), including their ethoxy and chloro variants. Other silanes that can be used for SAMs include poly(ethylene glycol) (PEG)-conjugated variants. Those skilled in the art will recognize that other alternatives exist, and these are considered within the scope of the present disclosure. Exemplary SAMs can comprise a thickness of at least 0.5 nm or greater. Preferably, the SAM readily bonds to the locally patterned interfacial layer, but does not readily bond to other adjacent material layers (e.g., hermetic layer, piezoelectric material, and / or blocking material layer).

[0054] When using electrodes and / or interfacial layers containing gold or another noble metal, thiol-based (e.g., alkanethiols) SAMs can be used. Alkanethiols are molecules with an alkyl chain as the backbone, a tail group, and an SH head group. Due to sulfur's strong affinity for these metals, thiols are useful in noble metal interfacial layers. Examples of useful thiol-based SAMs include, but are not limited to, 1-dodecanethiol (DDT), 11-mercaptoundecanoic acid (MUA), and hydroxyl-terminated (hexaethylene glycol)undecanethiol (1-UDT). These thiols contain the same backbone but different end groups—methyl (CH3), carboxyl (COOH), and hydroxyl-terminated hexaethylene glycol (HO-(CH2CH2O)6) for DDT, MUA, and 1-UDT, respectively. In certain embodiments, a SAM can be formed by incubating a gold surface in a thiol solution using a suitable solvent (e.g., anhydrous ethanol).

[0055] After forming the SAM, the SAM can be biologically functionalized, for example, by receiving at least one specific binding material. In certain embodiments, the specific binding material can be applied to or above the SAM using a microarray spotting needle or other suitable method. In certain embodiments, the interface layer can have a high-dimensional-tolerance pattern (e.g., using photolithography to define the interface layer) on only a portion of the resonator structure (including the substrate). The SAM can be applied to the interface layer, and the subsequently applied specific binding material can adhere only to the SAM. In certain embodiments, the patterning of the interface layer can provide higher dimensional tolerance for positioning the specific binding material than can be achieved through microarray spotting alone. Examples of specific binding materials include, but are not limited to, antibodies, receptors, and ligands. The specific binding material is preferably configured to receive a predetermined target substance (e.g., a molecule, protein, DNA, virus, bacteria, etc.). The functionalized material including the specific binding material can have a thickness ranging from about 5 nm to about 1000 nm, or from about 5 nm to about 500 nm. In certain embodiments, an array of different specific binding materials can be provided on different active regions of a multi-resonator structure (i.e., one or more resonator structures comprising multiple active regions), optionally in combination with one or more active regions lacking specific binding material to serve as comparison (or "reference") regions. In certain embodiments, a functionalized material (e.g., a chemically functionalized material) can provide nonspecific binding utility.

[0056] Certain embodiments relate to a fluidic device comprising a plurality of BAW MEMS resonator structures as disclosed herein, and comprising a fluidic channel (e.g., a channel, a chamber, etc.) arranged to direct a liquid into contact with at least one functionalized (e.g., specifically binding) material disposed on at least one active region of the resonator structure. Such a device can be microfluidic in scale and include at least one microfluidic channel (e.g., having at least one dimension (e.g., height and / or width) no greater than approximately 500 microns, or approximately 250 microns, or approximately 100 microns). For example, after fabricating the BAW MEMS resonator structures and depositing a SAM on portions thereof (optionally before depositing an airtight layer and an interface layer), the microfluidic device can be fabricated by forming one or more walls defining lateral boundaries of a microfluidic channel on the first BAW MEMS resonator structure, wherein the active region is disposed along the bottom surface of the microfluidic channel, and then enclosing the microfluidic channel using a protective layer or cover layer. The protective layer or cover layer can define a fluid port (e.g., an opening) that enables fluid communication with the microfluidic channel. In some embodiments, a functionalizing (e.g., specific binding) material may be pre-applied to the active region of the BAW MEMS resonator structure before forming the microfluidic channel; in other embodiments, the functionalizing material may be applied to the active region of the BAW resonator structure after forming the microfluidic channel.

[0057] The walls of the microfluidic channels can be formed from any suitable material (e.g., a thin polymer material and / or a laser-cut "stencil" layer of a laminate), optionally including one or more self-adhesive surfaces (e.g., tape). Optionally, such walls can be formed using SU-8 negative epoxy resist or other photoresist materials prior to deposition of the SAM layer, functionalizing material, and / or blocking layer. In certain embodiments, a cover or protective layer can be integrally formed with one or more walls (e.g., by molding or other suitable processes) to define a portion of the upper boundary and lateral boundaries of at least one fluidic channel, and an integrally formed partial cover / wall structure can be applied (e.g., adhered or otherwise bonded) over at least a portion of the BAW resonator structure to enclose the at least one fluidic channel.

[0058] In certain embodiments, a chemical or biological blocking material can be applied to a portion of the SAM to prevent the functionalized (e.g., specific binding) material from attaching to one or more selected regions of the BAW resonator structure (e.g., one or more regions other than the active region). The appropriate choice of chemical or biological blocking material (e.g., blocking buffer) for a given analysis depends on the type of target substance or analyte present in the sample. Various types of blocking buffers (e.g., highly purified proteins, serum, or milk) can be used to block free sites on the SAM. Other blocking agents include ethanolamine or polyethylene oxide (PEO)-containing materials. An ideal blocking buffer will bind to all potential sites of nonspecific interaction away from the active region. To optimize the blocking buffer for a specific analysis, empirical testing can be used to determine the signal-to-noise ratio. Because each antibody-antigen pair has unique properties, no single chemical blocking material is suitable for all situations.

[0059] Figure 4The present invention is a schematic cross-sectional view of a portion of a fluidic device 70 (e.g., a biochemical sensor device) including a microfluidic channel 72 bounded from below by a bulk acoustic wave (BAW) MEMS resonator structure including an active region 50, laterally bounded by walls 64, and bounded from above by a cover or protective layer 66 defining fluid ports 68A, 68B. The device serves as a comparative device and is intended to provide context for the embodiments of the present disclosure described later. The fluidic device 70 includes a substrate 32 covering an acoustic reflector 34 and a bottom-side electrode 40 generally disposed below a piezoelectric material 42. A top-side electrode 48 extends over a portion of the piezoelectric material 42, wherein a portion of the piezoelectric material 42 disposed between the top-side electrode 48 and the bottom-side electrode 40 represents the active region 50 of the BAW MEMS resonator structure. The top-side electrode 48 and the piezoelectric material 42 are covered with an airtight layer 52, an interface layer 54, and a self-assembled monolayer (SAM) 56. The portion of SAM 56 between active area 50 and wall 64 is covered with a chemical or biological blocking material 60 to prevent localized attachment of functionalized material and / or analytes. A portion of SAM 56 aligned with active area 50 is covered with a layer 58 of functionalized (e.g., specific binding) material arranged to bind at least one analyte. Wall 64, laterally displaced from active area 50, extends upward from chemical or biological blocking material 60 to define the lateral boundaries of microfluidic channel 72 containing active area 50. If wall 64 is formed on SAM 56, SAM 56 can facilitate adhesion of wall 64. Wall 64 can be formed from any suitable material, such as a thin polymer material and / or a laser-cut "template" layer of a laminate, optionally including one or more self-adhesive surfaces (e.g., tape). Alternatively, such wall 64 can be formed prior to deposition of SAM 56, layer 58 of functionalized material, and chemical or biological blocking material 60 with SU-8 negative epoxy resist or other photoresist material. A covering or protective layer 66 defining upper surface fluid ports 68A, 68B is also provided to provide an upper boundary for the microfluidic channel 72. The covering or protective layer 66 can be formed by defining the ports in a layer of a suitable material (e.g., a substantially inert polymer, glass, silicon, ceramic, etc.) (e.g., by laser cutting or water jet cutting) and adhering the covering or protective layer 66 to the top surface of the wall 64.

[0060] As mentioned previously, it can be difficult to achieve a high degree of alignment between the functionalized material and the active area of ​​the MEMS resonator device by relying solely on microarray spotting. Figure 4As shown, the laterally extending portions 58' of the functionalized material layer 58 extend laterally beyond the active area 50 of the BAW MEMS resonator device and can be used to bind analytes contained in the fluid within the microfluidic channel 72. The laterally extending portions 58' of the functionalized material layer 58 constitute excess functionalized (e.g., specific binding) material that can reduce sensor response, for example by compromising the lower limit of detection by binding analytes supplied to the active area 50 before they are delivered to the active area 50. Even if there is no excess functionalized material outside the lateral extent of the active area 50, the presence of the functionalized material layer 58 over the entire active area 50 may tend to compromise the lower limit of detection due to the reduced sensitivity of the active area 50 away from its center point or center region. As previously discussed in conjunction with Figures 1A-1C As described above, when functionalized material is provided along the entire active area and a fluid containing analyte is arranged to flow parallel to the upper surface of the active area, the analyte may tend to accumulate along the leading edge of the functionalized material near the radial boundaries of the active area. Binding of analyte to functionalized material disposed near the radial boundaries of the active area can reduce or eliminate the presence of analyte available for binding to functionalized material disposed at the center point or region of the active area, particularly if the analyte concentration is very low. Given a Gaussian (or similar) sensitivity profile, the presence of analyte accumulation at the leading edge of the active area, combined with the absence of analyte binding to functionalized material near the center point of the active area, will result in a limited (low) aggregation response for sensors containing an active area.

[0061] When using the fluidic device 70, a fluid sample can be supplied into the microfluidic channel 72 above the active area 50 via the first fluid port 68A and exit the microfluidic channel 72 via the second fluid port 68B. Due to the laminar nature of fluid flow within the microfluidic channel 72, the fluid volume can be modeled and represented as a "stack" of horizontal fluid layers, including a lowermost fluid layer 74A and an uppermost fluid layer 74N. Analytes contained in the lowermost fluid layer 74A of the fluid sample will tend to bind to and accumulate at the lateral extension 58' of the functionalized material layer 58 disposed upstream of the active area 50. If the analyte concentration in the sample is low, the lowermost fluid layer 74A may be depleted of analytes after the analytes bind and accumulate at the leading edge of the functionalized material along the periphery of the active area 50. Analytes contained in fluid layers above the lowermost fluid layer 74A (including the uppermost fluid layer 74N) may be unable to bind to the functionalized material layer 58 because diffusion of the analytes between the fluid layers 74A-74N (e.g., in the vertical direction) may occur slowly. As a result, the analyte concentration in the sample may need to be relatively high so that any analyte can bind to the functionalized material layer 58 disposed at the center point of the active area 50. Assuming there is sufficient analyte bound to the functionalized material layer 58 disposed above the active area 50, when bulk acoustic waves are induced in the active area 50 by providing an electrical (e.g., AC) signal to the bottom and top electrodes 40, 48, a change in at least one of the frequency, amplitude, or phase characteristics of the BAW resonator structure can be detected to indicate the presence and / or amount of analyte bound to the functionalized material layer 58. If no analyte binds to the functionalized material layer 58 near the center point of the active area 50, the sensor response may be low or difficult to detect.

[0062] To overcome limitations associated with the presence of functionalized material disposed on peripheral portions of the resonator's active area (and excess functionalized material extending laterally beyond the active area), embodiments disclosed herein limit the presence of functionalized material to less than the entire active area by omitting the functionalized material from at least one peripheral portion of the resonator's active area. Methods for limiting the location of the functionalized material to less than the entire active area may include, for example, patterning an interface layer over less than the entire active area (e.g., providing the interface layer along a central portion of the active area, but not along one or more peripheral portions of the active area); patterning a blocking layer on one or more peripheral portions of the active area, either on the interface layer or the SAM; patterning a SAM over less than the entire active area; or a combination of one or more of the foregoing. As techniques for depositing functionalized material with higher resolution than conventional microarray spotting have been developed, such techniques may also be used to limit the location of the functionalized material to less than the entire active area.

[0063] Figures 5A-5F Shows the combination according to Figure 2 Fabrication of a fluidic device (e.g., a biochemical sensor device) with a bulk acoustic wave MEMS resonator structure, each figure shows the structure after completion of a fabrication step, and the fluidic device including functionalized material is arranged over a central portion of the active area of ​​the BAW resonator structure, but less than the entire active area.

[0064] Figure 5A After the airtight layer 52 is deposited on the surface of the top side electrode 48 and the piezoelectric material 42, Figure 2 Schematic cross-sectional view of a portion of a BAW resonator device of FIG. 3 , including substrate 32 , acoustic reflector 34 , piezoelectric material 42 , and bottom and top electrodes 40 , 48 . An airtight layer 52 extends over the active region 50 and the remainder of the piezoelectric material 42 . Figure 5B The following diagram shows the interface layer 54 after deposition on the airtight layer 52. Figure 5A The BAW resonator device portion of the embodiment of the present invention. In certain embodiments, the hermetic layer 52 and / or the interface layer 54 can be applied by one or more deposition processes, such as atomic layer deposition (ALD), chemical vapor deposition (CVD), or physical vapor deposition (PVD), wherein these layers 52, 54 are applied sequentially, optionally in a vacuum environment. The hermetic layer 52 preferably comprises an oxide, nitride, or oxynitride material that serves as a dielectric material and has a low water vapor transmission rate. The interface layer 54 preferably comprises a hydroxylated oxide surface suitable for receiving a SAM, or gold or other precious metal. Figure 5C After forming the wall 64 on the interface layer 54 Figure 5B A BAW resonator device portion is shown in which walls 64 are laterally displaced relative to the active region 50 to define the lateral boundaries of the microfluidic channel containing the active region 50. Such walls 64 can be formed from any suitable material (e.g., a thin laser-cut "template" layer of polymer material and / or laminate material), optionally including one or more self-adhesive surfaces (e.g., tape), or using SU-8 negative epoxy resist or other photoresist material.

[0065] Figure 5D Shown after forming a self-assembled monolayer (SAM) 56 over the interface layer 54 between the walls 64 and after applying a layer of functionalized material 58 only on the central portion 76 of the active area 50 Figure 5C The BAW resonator device part. Figures 10 to 12A Methods of applying the functionalized material only on the central portion of the active area and on the SAM layer extending beyond the functionalized material are discussed. Figure 6 Methods of applying a functionalized material only on a central portion of an active area are discussed, wherein one or more underlying layers (eg, a SAM layer and an interface layer) are also disposed on the central portion of the active area.

[0066] Figure 5E The SAM 56 is shown after applying a chemical or biological blocking material 60 to the portion of the SAM 56 that was not previously covered with the functionalized material layer 58. Figure 5D The chemical or biological blocking material 60 extends over a peripheral portion of the active region 50 , not coincident with the central portion 76 , and further extends over an inactive region between the active region 50 and the wall 64 . Figure 5F Shown after adding a cover or protective layer 66 disposed on the top surface of the wall 64 to form the fluidic device 78. Figure 5E The cover or protective layer 66 defines fluid ports 68A, 68B adapted to allow a fluid (e.g., a liquid) containing a target substance to be introduced into the microfluidic channel 72 containing the active area 50, wherein the functionalized material layer 58 is disposed on a central portion 76 of the active area 50.

[0067] Figure 5G Shown Figure 5F A fluidic device 78 is provided in which an analyte 62 binds to the functionalized material layer 58, such as may occur after a fluid containing the analyte 62 (or target substance) flows into the microfluidic channel 72 (via one of the fluid ports 68A, 68B) to contact the functionalized material layer 58. When bulk acoustic waves are induced in the active region 50 by providing an electrical (e.g., alternating current) signal to the bottom and top electrodes 40, 48, a change in at least one of the frequency, amplitude, or phase characteristics of the BAW resonator structure can be detected to indicate the presence and / or amount of the analyte 62 bound to the functionalized material layer 58. Because the functionalized material layer 58 is disposed only on the central portion 76 of the active region 50 and is highly sensitive to changes in adsorbed mass, and the peripheral portions of the active region 50 are free of adsorbed analyte, the fluidic device 78 is configured to provide a relatively large signal change in response to binding of the analyte 62 to the functionalized material layer 58.

[0068] Figure 6 Shown with Figure 5F and 5GAnother fluidic device 80 is similar to the fluidic device 78 shown in FIG, in which not only the functionalized material layer 58 but also the interface layer 54 and the SAM 56 are disposed only on the central portion 76 of the active area 50. The fluidic device 80 includes a substrate 32, an acoustic reflector 34, a piezoelectric material 42, bottom and top electrodes 40, 48, and a gas barrier layer 52 on the surface of the top electrode 48 and the piezoelectric material. A wall 64 laterally displaced relative to the active area 50 extends upward from the gas barrier layer 52, and a capping or protective layer 66 defining fluid ports 68A, 68B is disposed (e.g., adhered) to the top surface of the wall 64 to surround the microfluidic channel 72 containing the active area 50 covered with the functionalized material layer 58. The interface layer 54 can be deposited by any suitable deposition technique disclosed herein (e.g., ALD, CVD, or PVD), preferably in combination with one or more masks (e.g., photolithographic and / or mechanical masks) to precisely control its placement only on the central portion 76 of the active area 50. Interfacial layer 54 preferably comprises a hydroxylated oxide surface or comprises gold or other noble metal suitable for attaching thiol-based SAMs. Hydroxated oxide surfaces are suitable for attaching organosilane-based SAMs. After forming interfacial layer 54, self-assembled monolayer (SAM) 56 may be deposited thereon, optionally in conjunction with one or more masks to control the placement of interfacial layer 54 only on SAM 56 aligned with central portion 76 of active area 50. Optionally, one or more blocking materials (not shown) may be patterned on areas of hermetic layer 52 not covering interfacial layer 54 and SAM 56. After forming SAM 56, functionalizing material 58 may be deposited on SAM 56. Because functionalizing material 58 tends to require SAM 56 for adhesion, functionalizing material 58 will tend to deposit only on SAM 56 above central portion 76 of active area 50. If desired, one or more photolithographic or mechanical masks may optionally be used during application of functionalizing material 58.

[0069] 7A to 9C The active area of ​​a fluidic device containing a BAW resonator structure is shown, where the central portion of the active area is covered with functionalized materials in three different configurations, and Figures 8A to 9C Also included are hollow arrows indicating the direction of fluid flow relative to the corresponding active area. Although three specific configurations are shown (i.e., Figures 7A-7C 、 Figures 8A-8C and Figures 9A-9C ), it will be appreciated that the functionalized material may be provided on the central portion of the active region in any suitable shape or configuration within the scope of the appended claims. Furthermore, while the active region is shown as having a circular shape for ease of disclosure, it will be appreciated that the active region of the resonator structure is not limited thereto and may include any suitable rectangular, trapezoidal, elliptical, curved, or other geometric shape.

[0070] Figure 7A FIG. 5 is a schematic top plan view of an active region 50A of a fluidic device incorporating a BAW resonator structure, wherein a central portion 76A (circular) of the active region 50A is covered with functionalized material 58A arranged in a symmetrical circular configuration, and an annular peripheral portion 84A of the active region 50A is free of functionalized material, according to one embodiment. The active region 50A includes a maximum width W a and the maximum length L a , and the functionalized material includes a maximum width W f and the maximum length L f . The active area 50A includes a center point 82A having maximum sensitivity, which coincides with the center of the central portion 76A covered with the functionalized material 58A. The functionalized material 58A is arranged in a shape including a curved leading edge, wherein the center point 76A' of the curved leading edge is arranged between the center point 82A of the active area 50A and the inlet (not shown) of the fluidic device containing the active area 50A. Although the central portion 76A is symmetrical and concentric with the active area 50A, in alternative embodiments, the central portion covered with the functionalized material can be asymmetrical and / or non-concentric relative to the associated active area. In addition, although the leading edge of the functionalized material 58A is arranged in a curved shape, it should be understood that the leading edge can be made into any suitable shape, such as straight, angled, serrated, or other geometric configurations. Figure 7B and 7C Provided separately Figure 7A Schematic cross-sectional side and front views of a functionalized material 58A and an active area 50A, wherein the functionalized material 58A is disposed over a central portion 76A of the active area 50A, and the central portion 76A is surrounded by a peripheral portion 84A that is free of functionalized material.

[0071] Figure 8A FIG. 5 is a schematic top plan view of an active region 50B of a fluidic device incorporating a BAW resonator structure, according to one embodiment, wherein a central portion 76B (circular) of the active region 50B is covered with a functionalized material 58B, the functionalized material 58B being arranged in an elliptical configuration with a width greater than a length, a maximum width of the active region greater than the maximum width of the functionalized material 58B, and a peripheral portion of the active region being free of functionalized material. The active region 50B includes a maximum width W a and the maximum length L a , and the functionalized material 58B includes a maximum width W f and the maximum length L f As shown in the figure, W f >L f , W a >Wf , L a >L f Active region 50B includes a center point 82B having maximum sensitivity, with center point 82B coinciding with the center of central portion 76B covered by functionalized material 58B. Figure 8B and 8C Provided separately Figure 8A Schematic cross-sectional side and front views of an active area 50B and functionalized material 58B, wherein the functionalized material 58B is disposed over a central portion 76B of the active area 50B, and the central portion 76B is surrounded by a peripheral portion 84B that is free of functionalized material. The functionalized material 58B is disposed in a shape including a curved leading edge, wherein a center point 76B′ of the curved leading edge is disposed between a center point 82B of the active area 50B and an inlet (not shown) of a fluidic device containing the active area 50B.

[0072] Figure 9A is a schematic top plan view of an active region 50C of a fluidic device incorporating a BAW resonator structure, according to one embodiment, wherein a central portion 76C of the active region 50C is covered with a functionalized material 58C, the functionalized material 58C being arranged in an elongated elliptical configuration having a width greater than its length, the maximum width of the active region 50C being equal to the maximum width of the functionalized material 58C, and the crescent-shaped front and rear peripheral portions 84C of the active region 50C being free of functionalized material. The active region 50C comprises a maximum width W a and the maximum length L a , and the functionalized material 58C includes a maximum width W f and the maximum length L f As shown in the figure, W f >L f , W a =W f , L a >L f Active region 50C includes a center point 82C having maximum sensitivity, wherein center point 82C coincides with the center of central portion 76C covered with functionalized material 58C. Figure 9B and Figure 9C Provided separately Figure 9A Schematic cross-sectional side and front views of an active area 50C and functionalized material 58C, wherein the functionalized material 58C is disposed on a central portion 76C of the active area 50C, and the central portion 76C is bounded front and back by crescent-shaped front and rear peripheral portions 84C that are free of functionalized material. The functionalized material 58C is disposed in a shape including a curved leading edge, wherein a center point 76C′ of the curved leading edge is disposed between a center point 82C of the active area 50C and an inlet (not shown) of a fluidic device containing the active area 50C.

[0073] Compare Figure 7A 、 8A and the configuration shown in 9A, Figure 7A A circular configuration with central portion 76A of functionalized material 58A may exhibit higher sensitivity than if the entire active area 50A were covered with functionalized material 58A, but sensitivity may not be optimal for very low analyte concentrations because the leading edge of functionalized material 58A (at the boundary between peripheral portion 84A and central portion 76A) is significantly closer to the side edge of active area 50A than central point 82A. Additionally, the absence of functionalized material along a subset of peripheral portion 84A means that some analytes may travel directly over peripheral portion 84A without interacting with any functionalized material 58A. Figure 8A The oval configuration of the central portion 76B with the functionalized material 58B may require more Figure 7A The configuration shown in FIG5 provides enhanced sensitivity because the leading edge of the functionalized material 58B (at the boundary between the peripheral portion 84B and the central portion 76B) is closer to the center point 82B than the side edges of the active area 50B, which causes any initial analyte accumulation on the leading edge of the functionalized material 58B to be greater than that on the central point 82B. Figure 7A However, the absence of functionalized material along a subset of the peripheral portion 84B means that some analytes may travel immediately over the peripheral portion 84B (i.e., at its narrowest portion) without interacting with (i.e., binding to) any functionalized material 58B. Figure 9A The elongated oval configuration of the central portion 76C with the functionalized material 58C may be more Figure 8A The configuration has an even higher sensitivity. Because the entire width W of the active area a The presence of functionalized material 58C thereon means that any analyte traveling directly over active area 50C is likely to interact with (ie, bind to) some of functionalized material 58C.

[0074] Figure 10 -12 shows a method for controlling the localized deposition of a self-assembled monolayer (SAM) to enable the SAM to be placed over less than the entire active area of ​​a resonator, thereby enabling a functionalized material covering the SAM to be similarly placed over less than the entire active area.

[0075] Figure 10is a schematic side cross-sectional view of the active region 50 of the BAW resonator structure, with a mechanical mask 86 defining windows 88 disposed thereon to allow a precursor material 90 for the self-assembled monolayer 56 to be deposited through the windows 88 on the central portion 76 of the active region 50 without forming a SAM on the peripheral portion 84 of the active region 50. After forming the SAM 56, the mechanical mask 86 may be removed. The one or more windows 88 may be formed in the mechanical mask 86 by any suitable means, such as etching, laser cutting, water jet cutting, etc.

[0076] Figure 11 FIG. 1 is a schematic side cross-sectional view of the active region 50 of the BAW resonator structure, which is covered with a patterned photoresist layer 92 to allow the precursor material 90 of the SAM 56 to be deposited on the central portion 76 of the active region 50 through windows 94 in the photoresist, without forming a SAM on the peripheral portion 84 of the active region 50. The windows 94 in the photoresist layer 92 can be formed by photolithographic etching or other conventional means. After forming the SAM 56, the photoresist layer 92 can be removed, preferably by a chemical method that does not tend to degrade the SAM 56. In some embodiments, during the removal of the photoresist layer 92, one or more removable protective layers (e.g., a reverse mechanical mask or a chemical coating) can be disposed over the SAM 56 to prevent degradation of the SAM 56, and then the protective layers can be removed.

[0077] Figure 12A is a schematic side cross-sectional view of active region 50 of a BAW resonator structure covered with organosilane-based SAM 56, wherein a radiation blocking mechanical mask 96 is disposed over SAM 56 and an electromagnetic radiation source 98 is positioned to transmit a beam 98A through apertures (openings) or boundaries of mechanical mask 96 to selectively remove portions of SAM 56. In certain embodiments, electromagnetic radiation source 98 is configured to emit electromagnetic radiation in the ultraviolet range including a peak wavelength in the range of approximately 150 nm to 400 nm. Figure 12B is after the SAM 56 is removed along the peripheral portion 84 of the active area 50 to cause only the central portion 76 of the active area 50 to be covered with the SAM 56 Figure 12A Schematic side cross-sectional view of active region 50 of a BAW resonator structure. In some embodiments, a second mechanical mask (not shown) may be applied over SAM 56 covering central portion 76 of active region 50, with holes arranged over peripheral portion 84, and a blocking layer material (not shown) may be applied through at least one hole defined in the second mechanical mask to cover portions of the BAW resonator structure not covered by SAM 56 (e.g., including but not limited to peripheral portion 84 of active region 50).

[0078] Figure 13 is a bulk acoustic wave MEMS resonator device 30 (with Figure 2 FIG2 is a top plan view of a portion of a resonator device 30 (not shown in FIG2 ). The MEMS resonator device 30 includes a piezoelectric material (not shown) disposed above a substrate 32, a bottom-side electrode 40 disposed below a portion of the piezoelectric material, and a top-side electrode 48 disposed above a portion of the piezoelectric material, including an active region 50 in which the piezoelectric material is disposed between overlapping portions of the top-side electrode 48 and the bottom-side electrode 40. Externally accessible contacts 40A and 48A are in electrical communication with the bottom-side electrode 40 and the top-side electrode 48, respectively. After portions of the MEMS resonator device 30 are covered with an interfacial layer, self-assembled monolayer, and functionalized (e.g., specific binding) material as disclosed herein, the resonator device 30 can be used as a sensor and / or incorporated into a microfluidic device. If desired, multiple MEMS resonator devices 30 can be provided in an array on a single substrate 32.

[0079] Figure 14 1 is a perspective assembly diagram of a microfluidic device 100 incorporating a substrate 102 having a plurality of bulk acoustic wave MEMS resonator devices, an intermediate layer 120 defining a central microfluidic channel 122 aligned with active regions 108A-108N of the MEMS resonator devices, and a protective layer or cover layer 130 disposed over the intermediate layer 120. The top center portion of the substrate 102, which includes an acoustic reflector (not shown) and a piezoelectric material (not shown), includes a top-side electrode 106 and bottom-side electrodes 104A-104N. The region where the aforementioned electrodes overlap one another and the piezoelectric material is disposed therebetween comprises the active regions 108A-108N. Any suitable number of active regions 108A-108N may be provided and arranged in series or parallel fluidics, although Figure 14Five active regions are shown in FIG. The top peripheral (or top) portion of substrate 102 also includes a reference topside electrode 116 and a reference bottomside electrode 114 in communication with a reference overlap region 110. Such reference overlap region 110 is not exposed to fluid and exists to provide a basis for comparing signals obtained from active regions 108A-108N exposed to fluid within a central microfluidic channel 122. Substrate 102 is covered with an intermediate (e.g., wall-defining) layer 120, wherein central microfluidic channel 122 is configured to receive fluid and defines a peripheral chamber 124, which is arranged to cover reference overlap region 110 in a sealing manner. Intermediate layer 120 can be formed from any suitable material, such as SU-8 negative epoxy resist, other photoresist materials, or a laser-cut "stencil" layer of a thin polymer material, optionally including one or more self-adhesive surfaces (e.g., tape). The intermediate layer 120 also includes a lateral insertion region 126 that allows access to lateral portions of the topside electrode 106 and the bottomside electrodes 104A-104N when the microfluidic device 100 is assembled. The protective or cover layer 130 includes a lateral insertion region 136 aligned with the lateral insertion region 126 of the intermediate layer 120 and includes microfluidic ports 132, 134 that are accessible along the top surface 138 and aligned with the ends of the central microfluidic channel 122 defined in the intermediate layer 120 to allow fluid (e.g., liquid) to be supplied to the central microfluidic channel 122 above the active areas 108A-108N. Preferably, at least the electrodes 104A-104N, 106 are covered with a gas barrier layer, an interface layer, a self-assembled monolayer, and a functionalized (e.g., specific binding) material as disclosed herein. Microfluidic devices according to other configurations can be provided, as will be appreciated by those skilled in the art upon reading this disclosure.

[0080] Figure 15The figure is a schematic cross-sectional view of a film bulk acoustic resonator (FBAR) structure 140 including an active region 50, at least a portion of which is covered by an interfacial layer and a self-assembled monolayer (SAM) adapted to receive a functionalized material (e.g., a specific or nonspecific binding material), according to one embodiment. FBAR structure 140 includes a substrate 142 (e.g., silicon or another semiconductor material) defining a cavity 144, which is covered by a support layer 146 (e.g., silicon dioxide). A bottom electrode 40 is disposed on a portion of support layer 146. A piezoelectric material 42, preferably embodying a piezoelectric material with a tilted c-axis hexagonal crystal structure (e.g., AlN or ZnO), is disposed above bottom electrode 40 and support layer 146. A top electrode 48 is disposed on at least a portion of the top surface of piezoelectric material 42. The portion of piezoelectric material 42 disposed between top electrode 48 and bottom electrode 40 represents the active region 50 of FBAR structure 140. The active region 50 is disposed on and aligned with a cavity 144 disposed below a support layer 146. The cavity 144 serves to confine acoustic waves induced in the active region 50 by preventing acoustic energy from dissipating into the substrate 142 because the acoustic waves cannot effectively propagate through the cavity 144. In this regard, the cavity 144 provides Figure 2 and 4 -6 is an alternative to the acoustic reflector 34. Although Figure 15 The cavity 144 is shown as being defined from below by a thinned portion of the substrate 142, but in alternative embodiments, at least a portion of the cavity 144 may extend through the entire thickness of the substrate 142. The steps for forming the FBAR structure 140 may include defining the cavity 144 in the substrate 142, filling the cavity 144 with a sacrificial material (not shown), optionally followed by planarizing the sacrificial material, depositing a support layer 146 over the substrate 142 and the sacrificial material, removing the sacrificial material (e.g., by flowing an etchant through vertical openings defined in the substrate 142 or the support layer 146 or side edges of the substrate 142), depositing the bottom-side electrode 40 on the support layer 146, growing (e.g., by sputtering or other suitable methods) the piezoelectric material 42, and depositing the top-side electrode 48.

[0081] Figure 16 The FBAR structure 140 is formed after adding the airtight layer 52, the interface layer 54, the self-assembled monolayer 56 and the functionalized material layer 58 (eg, specific binding material) to at least a portion thereof. Figure 15 Schematic cross-sectional view of the FBAR structure 140. The functionalized material layer 58 is disposed only on the central portion 76 of the active region 50, and the interface layer 54 and the SAM 56 are similarly disposed only on the central portion 76. Figure 16As shown, binding of the analyte 62 to the functionalized material layer 58 may occur, for example, after exposure of the functionalized material layer 58 to an analyte-containing medium (eg, a liquid or other fluid), optionally as part of a microfluidic device.

[0082] Those skilled in the art will recognize improvements and modifications to the preferred embodiments of the present disclosure. All such improvements and modifications are considered to be within the scope of the concepts disclosed herein and the claims that follow.

Claims

1. A fluid device comprising: A microelectromechanical system (MEMS) resonator device, the MEMS resonator device comprising: substrate; a bulk acoustic wave resonator structure disposed on at least a portion of the substrate, the bulk acoustic wave resonator structure comprising a piezoelectric material, a top-side electrode disposed on a portion of the piezoelectric material, and a bottom-side electrode disposed between the piezoelectric material and the substrate, wherein a portion of the piezoelectric material is disposed between the top-side electrode and the bottom-side electrode to form an active area, the top-side electrode including an active area portion overlapping the bottom-side electrode and coinciding with the active area, the active area portion including an active area width, and the active area portion including an active area length extending perpendicular to the active area width; as well as at least one functionalized material disposed on at least a central portion of the topside electrode, wherein the at least one functionalized material has a maximum length extending in the range of about 40% to about 90% of the length of the active area and a maximum width extending in the range of about 70% to 95% of the width of the active area; as well as a fluid channel comprising the active area and arranged to direct a flow of liquid into contact with the at least one functionalized material, wherein the fluid channel is arranged to direct the flow of liquid from an inlet upstream of the active area to the active area in a direction substantially parallel to the length of the active area, The length of the fluid channel is greater than the length of the active area, and the width of the fluid channel is greater than the width of the active area. 2 . The fluidic device of claim 1 , wherein the maximum width of the at least one functionalized material exceeds the maximum length thereof. 3 . The fluidic device of claim 1 , wherein the MEMS resonator device further comprises a self-assembled monolayer disposed between the topside electrode and the at least one functionalized material. 4 . The fluidic device of claim 1 , wherein the MEMS resonator device further comprises an interface layer disposed between the topside electrode and the at least one functionalized material. 5 . The fluidic device of claim 4 , wherein the topside electrode comprises a non-noble metal, and the MEMS resonator device further comprises a hermetic layer disposed between the interface layer and the topside electrode.

6. The fluidic device of claim 4, wherein the MEMS resonator device further comprises a self-assembled monolayer disposed between the interface layer and the at least one functionalized material.

7. The fluidic device of claim 1, wherein the at least one functionalized material comprises a specific binding material or a non-specific binding material.

8. The fluidic device of claim 1, wherein the piezoelectric material comprises a c-axis having an orientation distribution that is primarily non-parallel to a normal to a face of the substrate.

9. The fluidic device of claim 1, wherein the MEMS resonator device further comprises at least one acoustic reflector element disposed between the substrate and the BAW resonator structure.

10. The fluidic device of claim 1, wherein the substrate defines a recess, and the MEMS resonator device further comprises a support layer disposed between the BAW resonator structure and the recess, wherein the active region is disposed on at least a portion of the support layer and at least a portion of the recess.

11. The fluidic device of claim 1 , wherein the MEMS resonator device further comprises a blocking layer disposed on a portion of the piezoelectric material that does not coincide with the active region.

12. A sensor comprising the MEMS resonator device according to claim 1.

13. The fluidic device of claim 1, wherein the at least one functionalized material is arranged in a shape comprising a leading edge, wherein a center point of the leading edge is arranged between a center point of the inlet and the active area.

14. A method for biological or chemical sensing, the method comprising: supplying a fluid containing a target substance into the fluidic channel of the fluidic device according to claim 1, wherein the supplying is configured to cause at least some of the target substance to bind to the at least one functionalized material; introducing a bulk acoustic wave into the active region; as well as A change in at least one of a frequency characteristic, an amplitude characteristic, or a phase characteristic of the BAW resonator structure is sensed to indicate at least one of a presence or an amount of a target substance bound to the at least one functionalized material.

15. A method of manufacturing a microelectromechanical system (MEMS) resonator device, the method comprising: forming a bulk acoustic wave resonator structure comprising a piezoelectric material, a topside electrode disposed on a portion of the piezoelectric material, and a bottomside electrode disposed between the piezoelectric material and a substrate, wherein the portion of the piezoelectric material is disposed between the topside electrode and the bottomside electrode to form an active area, the topside electrode comprising an active area portion overlapping the bottomside electrode and coinciding with the active area, the active area portion comprising an active area width, and the active area portion comprising an active area length extending perpendicular to the active area width; depositing at least one functionalized material disposed on at least a central portion of the topside electrode, wherein the at least one functionalized material has a maximum length extending in a range of about 40% to about 90% of the length of the active area and a maximum width extending in a range of about 70% to 95% of the width of the active area; as well as At least one wall is formed on a portion of the BAW resonator structure and defines a fluid channel covering the active area, wherein the fluid channel is arranged to direct a flow of liquid from an inlet upstream of the active area toward the active area in a direction substantially parallel to a length of the active area, and the fluid channel is arranged to direct the flow of liquid to contact the at least one functionalized material, and wherein a length of the fluid channel is greater than a length of the active area and a width of the fluid channel is greater than a width of the active area.

16. The method of claim 15, further comprising forming a self-assembled monolayer on at least a portion of the topside electrode before depositing the at least one functionalizing material, wherein the at least one functionalizing material is disposed on at least a portion of the self-assembled monolayer.

17. The method of claim 16, wherein forming a self-assembled monolayer on at least a portion of the top-side electrode comprises: applying the self-assembled monolayer on the top electrode; disposing a first mechanical mask over the self-assembled monolayer, wherein the first mechanical mask defines at least one first aperture through which at least a first portion of the self-assembled monolayer is exposed; as well as Electromagnetic radiation comprising a peak wavelength in the range of about 150 nm to 400 nm is transmitted through the at least one first aperture to interact with the at least one first portion of the self-assembled monolayer to facilitate removal of the at least one first portion of the self-assembled monolayer.

18. The method according to claim 17, further comprising: disposing a second mechanical mask over at least a portion of the BAW resonator structure including the active region, wherein the second mechanical mask defines at least one second aperture through which at least a second portion of the self-assembled monolayer is exposed; as well as A blocking layer is applied to the at least one second portion of the self-assembled monolayer through the at least one second aperture.

Images