WO2002075261A2

WO2002075261A2 - Method for monitoring the oscillatory characteristics of a microfabricated resonant mass sensor

Info

Publication number: WO2002075261A2
Application number: PCT/US2002/007765
Authority: WO
Inventors: Michael I. Nerenberg; Kelvin J. Liu
Original assignee: Molecular Reflection
Priority date: 2001-03-15
Filing date: 2002-03-15
Publication date: 2002-09-26
Also published as: WO2002075261A3; AU2002250325A1

Abstract

The present invention relates, in general, to methods for determining the oscillatory characteristics in a microfabricated, resonant sensor and, in particular, to utilizing interferometry techniques to provide optical, non-contact, non-invasive methods for detecting the frequency of an oscillatory element (4) in a resonant sensor. Methods may include laser Doppler vibrometry (8), Michelson interferometry, stroboscopic interferometry, etc. Using interferometry to characterize the oscillatory response of microfabricated resonant devices permits simplified fabrication of the resonant elements (4) as it eliminates the need for the incorporation of electromechanical transducers to monitor motion of the individual elements.

Description

METHOD FOR MONITORING THE OSCILLATORY CHARACTERISTICS OF A MICROFABRICATED

RESONANT MASS SENSOR

Field Of The Invention

The present invention relates, in general, to methods for determining the oscillatory characteristics of a resonant device. More particularly, it relates to detection of oscillatory characteristics in sensors for use in physical or chemical sensing.

Related Application Information

This application is related to U.S. Application Serial No. 09/812,111, entitled

"Method for Monitoring the Oscillatory Characteristics of a Microfabricated Resonant

Mass Sensor", filed on March 15, 2001. That application is incorporated herein by reference as if full set forth in this application.

Discussion Of Related Art

Interferometry is a common method for the characterization of motion in macroscopic structures. More recently, interferometric techniques have been applied to the characterization of motion in mechanical components of microelectromechanical systems (MEMS). Examples of the latter are the use of laser Doppler vibrometry to analyze natural frequencies of microfabricated cantilever beams (W. Jia, Z. Enyao, Second International Conference on Vibration Measurements by Laser techniques: Advances and Applications, Ancona, Italy, 1996, p; 31 8-325), to determine the voltage displacement relationship for a microfabricated actuator (Cheng-Hsien Liu, Aaron M. B), for transient characterization of surface deflection in micropump and scanning minor devices ( A. Klein et. al., SPIE v. 3411, p. 618-623), and as the sensing method in microfabricated sealed-cavity resonant microbeam pressure sensors (D.W. Bums et al, Sensors and Actuators A, 1995, v. 48, p. 179-186). Stroboscopic interferometry has been used to obtain 2-dimensional time-resolved images of the oscillation of a microfabricated torsional minor (Hart, M. R., Conant, R.A., Lau, K.Y., and MuUer, R.S., Stroboscopic interferometer system for dynamic MEMS characterization, UC Berkeley ERL Report May 1, 2000).

There are a variety of resonant devices for which the oscillatory characteristics are a sensitive function of the mass loading at the device surface and the viscoelastic and electrical properties of the surrounding media. These devices can therefore be employed for the characterization of fluid properties, characterization of surface coatings, and as chemical sensors that detect surface binding to the resonant element or to chemically selective layers attached at the surface of the resonant element. One class of such devices is acoustic wave devices in which the propagation of an acoustic wave through the bulk or across the surface of the device is affected by the quantity to be measured. The earliest examples of such resonant sensors are devices based on piezoelectric crystals, of which the most commonly employed device is a thickness-shear mode (TSM) resonator, also called a quartz crystal microbalance (QCM). The QCM typically comprises a thin disc of AT-cut quartz with electrodes patterned on both sides. As a result of the crystal orientation in this piezoelectric material, application of a voltage across the two electrodes causes a shear deformation of the crystal. If a sinusoidally varying voltage of the appropriate frequency is applied across the crystal, resonant shear modes of the device can be excited. The frequency of the resonance will be dependent on the geometry of the crystal as well as characteristics and interactions of the crystal surface including the mass attached at the surface and the viscoelastic properties of the crystal/solution interface. Such devices therefore can and have been used as sensitive mass balances. Examples of their use as such are to monitor deposition rates in vacuo (Sauerbray, Z. Phys., 1955, v. 155, p. 206-222) as well as for the measurement of airborne and dissolved species that adsorb to the crystal surface (Buttry, Applications of the Quartz Crystal Monitor to Electrochemistry and Electroanalytical Chemistry, v. 17, Bard, A.J. ed., Marcel Dekker, Lie, NY, 1991; Ward, Buttry, Science, 1990, v. 249, p. 1000). Other acoustic wave devices that have been demonstrated for the analytical characterization of fluid properties and, most commonly, the monitoring of surface adsorbed mass, are those dependent on the generation and monitoring of surface acoustic waves (SAW), acoustic plate waves (APW), and flexural plate waves (FPW). In SAW devices, transducers fabricated on the surface of a piezoelectric crystal excite and monitor driven or resonant oscillations of the unbounded surface layers. The displacement occurring as the surface layer oscillates is perpendicular to the surface of the crystal. The frequency of resonance or relative phase of this oscillation can be measured to determine the mass loading of the crystal surface (Kovnovich, S. et. al., Rev. Sci. histrum., 1977, v. 48 (7), p. 920; US43 12228: Methods of detection with surface acoustic wave and apparati therefore). APW and FPW oscillations occurring in thin single crystal quartz plates and thinned membranes, respectively, can also be excited and monitored electronically to create mass sensitive devices. Such devices have been demonstrated as useful chemical sensors in numerous applications (see, for example, US 5,051,645: Acoustic wave H₂0 phase-change sensor capable of self-cleaning and distinguishing air, water, dew, frost and ice.

Further examples of such devices may include quartz crystal microbalances (QCM) [Bruckstein, S.; Shay, M. Electrochim. Acta 30, 1295 (1985)], acoustic plate mode (A.PM) devices [Martin, S. J.; Ricco, A. 3.; Niemczyk, T.M., Frye, 0. C. Sensors and Actuators 20, 253-268 (1989)], flexural plate wave (FPW) devices [Wenzel, S. W. Applications of Ultrasonic Lamb Waves, Doctoral Dissertations, EECS Department, University of California, Berkeley, CA (1992)], surface acoustic wave (SAW) devices [Wohltjen, H. Sensors andAcutators 5, 307 (1984)].

Another class of resonant sensors used for the characterization of fluid properties and chemical sensing are mechanical assemblies in which the phase or resonant frequency of vibration of an element of the assembly is affected by the characteristics of the surrounding media and/or the element's mass loading. An example of an assembly that has been used in such a manner is a microfabricated cantilever beam (US 5,445,008, Microbar Sensor). The sensor comprises a piezoelectrically activated cantilever bar that is coated with a chemically selective layer. Upon exposure of the cantilever to a medium containing the target species for which the coating is selective, the target species will bind to the coating and thereby increase the mass loading on the cantilever. This will cause a shift in the resonant frequency of oscillation of the cantilever where the magnitude of the shift is proportional to the mass change. Another example of an assembled resonant mechanical device for use as a chemical sensor is given in U.S. Patent No. 5,912,181 entitled "Method for Molecular Detection Utilizing Digital Micromirror Technology". This patent describes a method of detecting and screening organic molecules and biologic pathogens by employing a digital micromirror device. A digital micromirror device ("DMD") comprises hundreds of thousands of torsional micromirrors, e.g., sixteen microns square, each fabricated on hinges on top of a static random access memory ("SRAM"). A molecular probe of known composition can be attached at the surface of each digital micromirror in the array. If each minor surface is derivatized with a different molecular probe, the micromirror device becomes an array of molecular probes. Upon exposure of the minor surfaces to a sample substance containing target molecules of interest, binding of the target molecule to the molecular probes with which the probe and target forms a stable complex increases the surface mass of the involved mirrors and causes a subsequent shift in the resonant frequency of those mirrors. By measuring the mass loading induced frequency shift at each site, it can be determined whether or not binding has occurred and, knowing .the identity of the previously attached molecular probes, the compounds for which a target-probe complex are formed can be identified.

For the above devices to function, a means of measuring the resonant characteristics of each sensing element must be available. This has been accomplished in acoustic wave devices by fabricating transducer electrodes on the oscillating surface to electronically monitor its motion and determine the resonant frequency of oscillation or the phase of oscillation relative to a driving signal. In mechanical assemblies, electromechanical transducers that comprise piezoelectric coatings or electrostatic proximity sensors have be employed to monitor the motion of the moving element. This requires at a minimum a single pair of electrodes and more often than not, multiple pairs of electrodes, piezo-membranes, integrated circuits, and complicated signal processing. In a device such as the digital micromirror device, where no such transducers or circuitry are found, external sensors must be used. Furthermore, for the operation of devices with integral electromechanical transducers in solution, additional structures must be fabricated on the device to allow operation in fluids to prevent solution contact, and therefore shorting, of the transducer electrodes.

With the use of cantilever devices, the reflection of a light diode beam from the tip of the cantilever to a center-crossing photo-diode has been used to determine the frequency of oscillation of the cantilever. Although this does provide a means by which the frequency of the cantilever motion can be determined, this measurement alone only partially reflects the impact of mass on the oscillatory characteristics of the sensor.

Summary Of The Invention The present invention is a method for characterizing the harmonic response of resonant sensors comprised of single or arrayed microfabricated elements for which the harmonic response is dependent on the mass or effective mass at the surface of the resonant element and/or the viscoelastic properties of the entire system. The method involves using optical interferometry to monitor the position or velocity of the resonant element(s) in the device during driven or resonant vibration of these element(s) to determine the phase of the oscillation of the resonant element(s) relative to the driving signal or to determine the frequency of resonance. Interferometry involves focusing light at the surface of the structure to be characterized and analyzing the pattern of interference created by light reflected from the surface and a reference beam. The interference between the light reflected from the surface and a reference beam gives rise to a spatial or temporal signal that is indicative of the instantaneous position or velocity of the moving element at the locations(s) of incidence. The said effects can be seen as interference or fringe patterns, frequency, wavelength or amplitude modulation, or reflected images. Monitoring this signal with time allows determination of the frequency at which the element is oscillating or the phase of its oscillation relative to a driving signal. Interferometry, therefore, provides an optical, non-contact, non-invasive method for characterizing the harmonic response of a device, such as a digital micromirror device, which has no built-in sensors that can be utilized to measure frequency.

Optical methods can also simplify the fabrication of resonant sensing devices by removing the need for on-chip electromechanical transducers and/or integrated electronics to monitor the motion of individual elements. In addition to ease of fabrication, optical detection offers benefits to devices that operate in fluidic environments where isolation of solution and electrodes / electronics is difficult, where the incorporation of piezo-membranes is difficult or will adversely affect the mechanical properties of the device, and where monolithic design and incorporation of integrated circuits is complex and costly. Removal of these structures can provide for greatly reduced cost, time, and complexity. Interferometric methods, however, can be used in the presence of fluids and, therefore, provides an alternative to complicated microfabrication to accommodate measurements in liquids.

An aspect of the invention involves a new method of use of a laser Doppler vibrometer to detect the motion of microfabricated resonant elements that are used as chemical, physical or biologic sensors. The method includes focusing a laser Doppler vibrometer at a location on a resonant element so that the direction of motion of the element is defined relative to the direction of the incident beam and measuring the change with time in the position or velocity of that element at that location. In this manner the phase, amplitude, and/or frequency of oscillation of the element may be ascertained and monitored.

Another aspect of the invention involves the extension of any general interferometry technique for use in characterizing the harmonic response of a microfabricated resonant sensor used in monitoring chemical, physical, or biologic measurands. Such techniques include but are not limited to Michelson interferometry, stroboscopic interferometry, thin-film interferometry, differential interference contrast, and the like.

Other features and advantages of the invention will be evident from reading the following detailed description, which is intended to illustrate, but not limit, the invention.

Brief Description Of The Drawings

The drawings illustrate the design and utility of preferred embodiments of the present invention, in which similar elements are referred to by common reference numerals.

FIG. 1 is a perspective and partially schematic view of an embodiment of a system using a laser Doppler vibrometer for characterizing an arrayed resonant mass sensor based on the Texas Instruments digital micromirror device.

FIG. 2 is a perspective view of a section of a digital micromirror device according to an embodiment of the present invention.

FIG. 3 is an exploded perspective view of an embodiment of a single micromirror of the digital micromirror device illustrated in FIG. 2.

FIG. 4 is ah optical schematic of a Polytec OFN-5 12 Differential Fiber Interferometer. FIG. J is a block schematic of a Polytec OFV-3001 Vibrometer Controller.

FIG. 6 is a chart of measurement ranges for Polytec velocity decoders.

FIG. 7 is a chart of measurement ranges for Polytec displacement decoders

FIG. 8 are graphs of the damped sinusoidal response of a loaded versus unloaded micromirror in a Texas Instruments digital micromirror device. FIG. 9 is a graph showing the frequency response of a digital micromirror device element as measured using a laser Doppler vibrometer (y-axis) due to mass loading (x- axis). Mass loading was accomplished through the deposition of polystyrene beads at the surface of the digital micromirror device element. Detailed Description Of The Preferred Embodiment Overview of System

With reference to FIG. 1, an embodiment of a system using a laser Doppler vibrometer ("LDN") and a microfabricated resonant device 4, to measure mass is shown. The laser Doppler vibrometer 8 may be used in conjunction with an oscillatory device 4 having an array of oscillatory elements 70 (FIG. 2) to measure the frequencies of the oscillatory elements 70 by transmitting laser light onto the oscillatory elements 70 and collecting laser light reflected therefrom. By comparing the transmitted light and the reflected light, the laser Doppler vibrometer 8 and a control unit 9 can determine the velocity of the oscillating element based upon the Doppler frequency shift of the reflected light induced by the moving structure. The resultant velocity waveform is representative of the oscillation of the structure. By monitoring the mass induced resonant frequency shift of the oscillatory elements 70, the mass of added compounds or elements may be determined. The laser Doppler vibrometer 8 may also be used to measure phase and amplitude values of the oscillatory elements 70 for the same purpose.

Use of Digital Micromirror Device as Test Structure

In the embodiment of the oscillatory device 4 shown, the oscillatory device 4 is a digital micromirror device ("DMD") and, more specifically, a Texas Instruments

DLPTM chip, hi alternative embodiments, other types of oscillatory devices maybe used. The oscillatory device or digital micromirror device 4 has a plurality of oscillatory elements or micromirrors 70 that may be employed as resonant mass sensors in biologic and chemical sensing of sample substances based on the detected frequencies of the micromirrors 70 by the laser Doppler vibrometer 8 after the sample substance has been applied to the micromirrors 70 and the micromirrors 70 are oscillated.

With reference specifically to FIGS. 2 and 3, the digital micromirror device 4 includes more than 500,000 individual micromirrors 70 configured in an X-Y array. For simplicity, only a 3 X 3 array is shown. Each micromirror 70 includes a square mirror 75 supported upon a yoke 80 by a mirror support post 85. To balance the center of mass of the mirror 75 on the yoke 80, the support post 85 extends downwardly from the center of mirror 75 and is attached to the center of the yoke 80. The yoke 80 is axially supported along its central axis by ends of torsion hinges 90. The other end of each torsion hinge 90 is attached to and supported by a hinge post 95. Together, mirror 75 and yoke 80 can be axially rotated approximately 10 degrees in either direction about the hinges 90 until a tip 100 of the yoke 80 meets a landing tip 105. The digital micromirror device 6 is described in greater detail in U.S. Patent No. 5,535,047 to Hornbeck, which is incorporated by reference herein as though set forth in full.

Use of Laser Doppler Vibrometer to Characterize Response With reference to FIG. 1-5, an embodiment of the laser Doppler vibrometer (8 of Fig. 1) and a method of using the same will now be described in more detail. The laser Doppler vibrometer (8 of Fig. 1) which is illustrated in Fig. 4, is an OFV-5 12 differential fiber optic laser Doppler vibrometer made by Polytec GmbH that is used in single-ended mode. The laser Doppler vibrometer includes a low power laser 205 to supply light 207 to a first beamsplitter 210. The beamsplitter 210 splits the light 207 into an object beam 215 and a reference beam 220 of approximately equal intensity. The object beam 215 passes through a second beamsplitter 225 and is then focused on an oscillatory element or micromirror 70 of the oscillatory device 4 in Fig. 2. As seen in Fig. 1, a Polytec OFV-070 Microscope Adapter 7, for example, allows attachment of the laser Doppler vibrometer 8 onto a standard microscope 6, for example an Olympus BX-40, so that standard microscope optics can be used to focus the beam. The use of lOOx metallurgic objectives allows direct focusing of the laser beam down to a 3 μm spot. Positioning of the beam is achieved through precision micrometers on the microscope adapter 7. Referring to Fig 4, the same lens assembly that directs the light to the oscillatory element collects light 233 backscattered from the micromirror 70. The backscattered light 33 is diverted by the second beamsplitter 225 towards a third beam splitter 235. At the third beam splitter 235, the backscattered light 233 from the micromirror 70 interferes or mixes with the reference beam 230. When not operating in differential mode, the reference beam 230 is focused on an intrinsic mirror surface that provides a static internal reference rather than an external reference 300. h differential mode, the reference object 300 may be a stationary point on the chip packaging or another micromirror in the array such that the use of the reference object serves to control for external vibrations, noise, etc. Backscattered light 233 from the micromirror 70 experiences a Doppler frequency shift that is proportional to the instantaneous velocity of the micromirror 70 in the direction of the laser beam. The induced Doppler frequency shift is proportional to the velocity by:

Δ _ u / ^~ where f is the frequency of the laser, c is the speed of light and u is the speed of the object. The frequency difference between the backscattered light beam 233 and the reference beam 220 shows up as a light intensity modulation, and depicted in Fig. 1 , which as depicted in Fig. 1, is converted by the OFV-3001 Vibrometer Controller 9 to an analog signal 10 that is directly proportional to the instantaneous velocity or displacement of the object. Two decoder cards, an OVD-20 500 and OVD-02 600 have been installed in the controller to perform this function. As seen in Fig. 5, the OVD-02 velocity decoder 600 performs the Doppler based velocity calculations while the OVD-20 displacement decoder 500 performs displacement calculations based upon more general interferometry, fringe counting and interpolation. As seen in Fig. 4, a Bragg cell 250 in conjunction with a prism may be used to introduce a static frequency shift, e.g., 40 MHz, onto the reference beam 220, in order to distinguish between motion toward and away from the laser Doppler vibrometer 8. This system has a bandwidth of 0 - 1.5 MHz, velocity resolution of 0.5 μm/s, and displacement resolution of 0.08 μm at micromirrors' resonant frequency of around 75 kHz. In accordance with either of the exemplary methods described above, referring back to Fig. 1, the laser beam 5 of the laser Doppler vibrometer 8 is projected onto each individual oscillatory element 70 of interest. This may be done, for example, by using the micrometers on the OFV-070 7 or the microscope stage to either scan the laser across the entire surface of the device or by moving the device itself and collecting data for each of the individual mirrors separately. The analog signal 10 (Fig. 1) output by the controller is captured and digitized by a Tektronix TDS-224 digital oscilloscope 11. The resultant digital waveform 12 is then sent by a serial rs-232 connection to pc-based data acquisition software 13 for waveform processing. The measured frequency of each individual oscillating element 70, after exposure to the sample substance, is characteristic of whether or not a target candidate is present on the element 70. The frequency may also be characteristic of other physical attributes (e.g., mass, viscosity, density, temperature, etc.) of a sample substance. Mass Loading of Micromirror

As a demonstration of this embodiment of this method and apparatus, 1 p.m diameter polystyrene beads purchased from Bang's Laboratories were attached to the surface of the micromirrors in a Texas Instruments digital micromirror device. The beads come packaged in deionized water and are diluted 100:1 in ethanol to promote fast drying after deposition and obtain even the desired coverage. The bead-ethanol solution was spayed onto the mirror surfaces using an atomizer 1 to get fine coverage over the mirror surfaces and to prevent fluid seepage into the underlying structures of the digital micromirror device. Knowing the average diameter of the beads (1.06 p.m) and density of the material (1.05 g/cc), the weight of each bead is calculated to be 5.24 x i0~'⁵ g. By counting the number of beads on each mirror, the increased mass due to the weight of the beads can be determined.

The mirrors are expected to behave as a simple harmonic resonator that obeys the equation:

2π V m where k is the effective spring constant and m is the effective mass. As the mass of the mirror is increased, the resonant frequency is expected to decrease with the square root of the mass. Since the underlying electrodes had not been exposed to fluid, the intrinsic electrostatic motors were utilized to drive the oscillation. Referring to Fig. 1, the internal drivers of a Boxlight 4802 projector 2 were used to input drive signals 3 into the DMD 4. Each of the mirrors 70 was given a transient shock, and the damped ring-down response was measured by the laser Doppler vibrometer 8. The laser Doppler vibrometer 8 was focused down to a 3 p.m spot on the corner of maximum displacement so that the largest possible amplitude of signal could be obtained. The normal component of the velocity of oscillation of the mirror was measured and displayed as a waveform 10 on the oscilloscope 11. Digitized waveforms 12 were then sent from the oscilloscope to a PC 13. Subsequent analysis of the data correlated the number of beads attached to each mirror and the resultant added mass with the resonant frequency of the respective mirror. Unloaded mirrors' resonant frequencies averaged 72 kHz while mirrors with 40 pg of mass loading experienced resonant frequency shifts of almost 4 kHz. Fig. 8 depicts transient decay waveforms of both loaded and unloaded mirrors. Note increased period of loaded mirrors. Fig. 9 is a graph showing the resonant frequency of the oscillating mirror (y-axis) as a function of the weight at the mirror surface. A clear correlation between mass loading and resonant frequency is seen.

Alternative Embodiments and Processes

The laser Doppler vibrometer can be used to characterize the harmonic response of any microfabricated device used for chemical, physical or biologic sensing. With the TI digital micromirror device as an example platform, each of the mirrors represents a single mass in a simple harmonic oscillator. Together, they represent an arrayed mass balance that can be used for chemical and biologic sensing. When used as a chemical sensor, gels may be placed on the mirror surfaces that selectively adsorb chemicals of interest. As chemicals are adsorbed into the gel layer, the effective mass of the mirror will increase, and the resonant frequency will decrease. This resonant frequency shift can be characterized by using the laser Doppler vibrometer and quantitatively correlated to the adsorption and desorption of chemicals from the gel. Biologic sensing may be accomplished in a similar manner by using biologic probes, such as antibodies, that are attached to the mirror surfaces and monitoring mass induced resonant frequency shifts due to binding of test substances to the probes at individual mirrors. Applications of chemical and biologic sensing include chemical vapor sensing and high throughput screening and assaying of small molecules, peptides, proteins, antibodies, oligonucleotides, DNA molecules, sugars (lectins), fats, cells, or reactive beads. In all of these applications, the laser Doppler vibrometer can be used to perform harmonic characterizations .

This approach may also be used to determine the physical characteristics of the system. While mass can greatly affect the resonant frequency of a mirror, it is not the only parameter that can affect the harmonic response. Other physical parameters of the surrounding system such as fluid viscosity, density, temperature, pressure and flow rate can also cause frequency and amplitude modulation. By using the laser Doppler vibrometer to monitor the harmonic response of the mirrors in consideration of these variables, such parameters can be accurately quantified.

Use of the laser Doppler vibrometer or any other form of optical interferometer as a detector in a resonant sensor is not limited to the Texas Instruments digital micromirror device application. Any similar or dissimilar microfabricated device that behaves as a harmonic oscillator or whose resonant response is similarly affected by environmental parameters can used. Interferometry can be used to characterize the effects of mass loading, viscosity, temperature, pressure, flow, and bulk properties on the resonant response of any microfabricated device such as QCMs, FPW, SAW, APM devices, cantilevers, microbeams, plates, membranes, switches, relays, etc. as described below. A typical cantilever device has operating frequencies between the tens to hundreds of kilohertz, dimensions in the tens to hundreds of microns, and deflections in the low micrometer range. For example, a silicon AFM cantilever tip 200 p.m long, 50 p.m wide, and 2 p.m thick would have a spring constant of 7.72 N/m and a 1~ mode natural frequency of 64, 799Hz. If used as a chemical or biosensor, a monolayer of adsorbed small molecules would cause a resonant frequency shift of 4 Hz. Assuming reasonable deflections in the micrometer range, velocities of oscillation would be around 1 m/s. These numbers easily fall within the operating ranges of a typical laser Doppler vibrometer, the results of which are demonstrated as shown in Fig. 6 and Fig. 7, which describe the bandwidth, resolution and operating parameters of commercial Polytec LD V decoders.

Acoustic wave devices have higher operating frequencies that usually lie in the MHz range and have much smaller displacement amplitudes. In these cases variations of the typical laser Doppler vibrometer are needed to accommodate the higher frequencies and lower amplitudes. Other types of interferometers may be better suited to high frequency applications above 30-40 MHz.

Although the laser Doppler vibrometer 8 has been described as a differential fiber optic laser Doppler vibrometer used in single-ended mode, other laser Doppler vibrometers may be used such as, but not by way limitation, differential vibrometers and scanning vibrometers. The differential vibrometer uses the interference of light beams reflected from two locations and therefore provides the difference in the position or velocity of those locations. This allows the determination of a frequency or phase shift of an element of the device relative to another, presumably reference, element. By using the vibrometer in differential mode, spurious vibrations due to unwanted environmental effects, nonspecific adsorption, drift, noise, etc. can be minimized by comparing the site of interest with a designated reference site. In this manner, only the difference in velocity or displacement between the two will be apparent and common sources of background or noise will be filtered. Scanning vibrometers can be used to rapidly obtain data over an entire array in an automated manner or to obtain more detailed information than simple point velocities and displacements such as phase and mode shape information of a single site in the array.

Other optical interferometry techniques may also be utilized such that the application dictates the choice of the appropriate technique. As an example, stroboscopic interferometry may be used to simultaneously monitor several resonant elements in a device comprised of an array of elements. In stroboscopic interferometry, an area of the device surface containing parallel elements is illuminated by a strobed light source. The interferogram created by the light reflected from the illuminated surface and a reference beam provides a two dimensional image of the instantaneous displacement across the surface of the device. A series of such inteferograms provides a time resolved image of the displacement where the resolvable time step corresponds to the strobe rate. The motion, phase, and frequency of parallel elements can therefore be determined simultaneously if the frequency of oscillation of the element is less than the strobe frequency.

Other techniques that can be used are differential interference contrast (DIC), thin film interference, Michelson interferometry, and the like. All of these methods can be used in a manner similar to the laser Doppler vibrometer embodiment described above to monitor the motion or position of an oscillating structure in a resonant sensor. Using an optical interferometer for determining the frequency of oscillatory elements of a resonant sensor is advantageous over conventional on-board sensors such , as electrostatic and piezo-transducers because the laser Doppler vibrometer is not in contact with the sample media or the device itself. Thus, the laser Doppler vibrometer is not negatively affected by surface properties and environmental conditions caused by the sample media. For example, liquid samples may short out the electrodes in electrostatic or piezo transducers, but optical measurements will not be affected so long as the incident light can penetrate the media. In addition, the laser Doppler vibrometer provides a non-invasive measurement that will not affect the oscillation of the device. It also eliminates the need to fabricate individual sensors and circuitry for each element in the array. Large arrays with built-in transducers require multiplexing of output signals, a plethora of electrodes, and/or piezo materials to couple mechanical and electrical signals are unnecessary when oscillation characteristics are measured by interferometers as described herein. While preferred embodiments and methods have been shown and described, it will be apparent to one of ordinary skill in the art that numerous alterations may be made without departing from the spirit or scope of the invention. Therefore, the invention is not limited except in accordance with the following claims.

Claims

We Claim:

1. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used as resonant mass sensors said method comprising exposing the resonant elements to a sample substance, inducing oscillation of the resonant elements, and measuring the oscillation characteristics of the resonant element by interferometry, wherein an interference signal resulting from electromagnetic radiation reflected by movement of the resonant element and a reference beam is used to characterize the motion of the elements to determine if the mass of the elements have changed, a change in the mass of the resonant element reflecting binding of the sample substance to the sensor elements.

2. The method of claim 1, wherein the step of measuring includes measuring the position or velocity of one or more oscillatory elements with a laser doppler vibrometer.

3. The method of claim 1, wherein the step of measuring includes simultaneously measuring the frequency, phase or amplitude of parallel resonant elements.

4. The method of claim 3, wherein a stroboscopic interferometer is used for interferometric monitoring.

5. The method of claim 1, wherein the step of measuring includes measuring the frequency, phase or amplitude of one or more oscillatory elements with an optical interferometry technique.

6. The method of claim 1, wherein the step of oscillating includes oscillating the oscillatory device through a range of frequencies, and the measuring step includes characterizing the harmonic response after the oscillatory elements are exposed to the sample substance.

7. The method of claim 1, wherein the step of oscillating includes oscillating the oscillatory device with a range of frequencies simultaneously, and the measuring step includes characterizing the harmonic response after the oscillatory elements are exposed to the sample substance.

8. The method of claim 7, wherein said range of frequencies are simultaneously oscillated with a white noise source.

9. The method of claim 1, wherein the step of oscillating includes oscillating ^•the oscillatory device with an impulse, and the measuring step includes characterizing the transient decay or change in the harmonic response of the oscillatory elements after the oscillatory elements are exposed to the sample substance.

10. The method of claim 1, wherein the oscillatory element is a microfabricated resonant element selected from the group consisting of a flexural plate, a membrane, a cantilever, and a microbeam.

11. The method of claim 1 , wherein oscillation of the resonant elements is induced by an on-board transducer.

12. The method of claim 1, wherein oscillation of the resonant elements is induced by an external actuator.

13. The method of claim 1 , wherein interferometric monitoring is performed through a mediating layer of a fluid.

14. The method of claim 1, wherein the sample substance is an analyte that binds to the surface of the resonant element.

15. The method of claim 14, wherein the analyte binds to the surface of the resonant element as a result of a interaction between the analyte and a specific probe previously attached at the surface of the resonating element.

16. The method of claim 15, wherein the molecular probe is selected from the group consisting of a drug, organic molecule, peptide, protein, antibody, oligonucleotide, DNA, sugar carbohydrate, fat, cell, or bead.

17. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used as resonant sensors of viscosity, density, temperature, or pressure said method comprising exposing the resonant elements to a sample liquid or gas, inducing oscillation of the resonant elements, and measuring the oscillation characteristics of the resonant element by interferometry, wherein an interference signal resulting from electromagnetic radiation reflected by movement of the resonant element and a reference beam is used to characterize the motion of the elements to determine the viscosity, density, temperature, or pressure of the sample.

18. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used fluid flow rate resonant sensors, said method comprising exposing the resonant elements to flowing fluid and measuring the oscillation characteristics of the resonant element by interferometry, wherein an interference signal resulting from electromagnetic radiation reflected by movement of the resonant element and a reference beam is used to characterize the motion of the elements to determine the fluid flow rate.

19. A method of use of a laser Doppler vibrometer to screen sample substances attached at the surface of the resonant elements for binding to specific target species, comprising the steps of: providing a laser Doppler vibrometer; determining the harmonic response of one or more oscillatory elements using the laser Doppler vibrometer after one or more probes attached to the one or more oscillatory elements are exposed to a sample substance potentially containing one or more molecular structures sought to be detected; identifying the presence or absence of molecular structure attached to one or more of the probes based on a harmonic characterization step.

20. The method of claim 19, wherein the step of determining the harmonic response includes measuring the resonant oscillation frequency, phase, amplitude, and/or a change in the characteristics of the prior qualities.

21. The method of claim 19, wherein the oscillation to be characterized is excited by a source such as harmonic sweep, white noise, or impulse.

22. The method of claim 19, wherein the step of identifying includes identifying the presence or absence of molecular structure attached to one or more of the probes by identifying the one or more oscillatory elements that have an altered harmonic response after the one or more oscillatory elements and attached probes are exposed to the sample substance.

23. The method of claim 19, wherein the oscillatory element is selected from the group consisting of a flexural plate, a membrane, a cantilever, and a microbeam.

24. The method of claim 19, wherein the oscillatory elements to be characterized are in contact with a fluid and interferometry is performed through the fluid.

25. A method testing whether a sample substance has bound to the surface of a resonant element of a mass sensor for binding to specific target species, comprising the steps of: providing a stroboscopic interferometer; determining the harmonic response of one or more oscillatory elements using the stroboscopic interferometer after one or more probes attached to the one or more oscillatory elements are exposed to a sample substance potentially containing one or more molecular structures sought to be detected; identifying the presence or absence of molecular structure attached to one or more of the probes based on harmonic characterization step.

26. The method of claim 25, wherein the step of measuring the oscillation frequency includes measuring the resonant oscillation frequency or a change in the resonant oscillation frequency.

27. The method of claim 25, wherein the oscillation to be characterized is excited by a source selected from the group consisting of harmonic sweep, white noise, and impulse.

28. The method of claim 25, wherein the step of characterizing the harmonic response includes measuring the oscillation frequency, phase, and/or amplitude or a change in the oscillation frequency, phase and/or amplitude and the step of identifying includes identifying any molecular structure attached to one or more of the probes by identifying the one or more oscillatory elements that have an altered harmonic response after the one or more oscillatory elements and attached probes are exposed to the sample substance.

29. The method of claim 25, wherein the oscillatory element is any microfabricated resonant element such as, but not limited to, a flexural plate, a membrane, a cantilever, a microbeam.

30. The method of claim 19, wherein the oscillatory elements to be characterized are in contact with a fluid and interferometry is performed through the fluid.

31. The method of claim 25, wherein a single resonant element is characterized.

32. The method of claim 25, wherein multiple resonant elements are characterized in parallel.

33. The method of claim 25, wherein the multiple resonant elements are characterized in serial.

34. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used as resonant sensors where the harmonic characteristics are used to characterize the motion of the element to determine binding constants in a biochemical assay.

35. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used as resonant sensors where the reflecting surface is submerged under a standing or a flowing liquid.

36. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements that are used as resonant sensors where the reflection of electromagnetic energy occurs through a mirror or partially reflective surface.

37. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements in a MEMS based detector.

38. A method of interferometrically monitoring the oscillation characteristics of microfabricated resonant elements used for high throughput screening applications.