Abstract:
An MEOMS sensing chip for optically detecting and measuring substances in fluid samples is disclosed. The MEOMS sensing chip includes a system for optically sensing substances in the fluid samples and a system for delivering the fluid samples to the sensing system. The sensing system includes a two-branch channel waveguide and a plurality of ring waveguides, each branch in the two-branch waveguide being used for evanescently coupling light energy into one of the ring waveguides. The delivering system includes a plurality of micro-channels and a plurality of micro-wells, the micro-channels being used for transporting the fluid samples to the micro-wells. Each micro-well is aligned with a respective ring waveguide and is used for exposing the fluid sample contained therein to the respective ring waveguide. Characteristics related to the evanescent coupling of the light energy into the ring waveguides, e.g., resonant frequencies of the ring waveguides, are used for detecting substances in the fluid samples.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates generally to systems for performing optical sensing, and more particularly to micro-machined electrical-optical-mechanical systems for high-resolution chemical and biological sensing applications. 
     2. Background 
     Recent advances in processes for micro-machining silicon have made it possible to implement complete micro-machined electrical-optical-mechanical systems (MEOMS) on a chip. For example, MEOMS have recently been developed that incorporate sensors for detecting substances and measuring related physical properties. An important advantage of such MEOMS is the ability to place interfaces, sensors, and signal processing circuitry on the same silicon substrate, thereby making these systems high speed, portable, and relatively low cost. 
     A traditional method of detecting chemical and biological substances and measuring related physical properties, which may be implemented as part of a MEOMS, involves an optical technique known as evanescent wave surface detection. Generally, evanescent wave surface detection includes applying a fluid sample to the surface of a waveguide. Frequently, the waveguide surface is coated with a chemically sensitive layer and the fluid sample is allowed to react with this layer. Next, light is coupled into the waveguide, and the light propagating through the waveguide causes evanescent wave fields to be produced that reach out into the fluid sample on the waveguide surface. Because the fluid sample applied to the waveguide surface changes the effective index of refraction of the waveguide, the light propagating through the waveguide undergoes a shift in phase. Accordingly, the fluid sample on the waveguide surface can be detected and properties relating to the fluid sample can be measured by measuring the phase shift of the light coupled out of the waveguide. 
     One optical technique for detecting chemical and biological substances that uses evanescent wave surface detection is disclosed in U.S. Pat. No. 5,120,131 issued Jun. 9, 1992 to Lukosz. That patent discloses a technique that includes applying a fluid sample to a waveguide surface and then coupling light into the waveguide, thereby causing evanescent wave fields to reach out into the fluid sample. Specifically, the light coupled into the waveguide is polarized so that it propagates through the waveguide as two mutually coherent and orthogonally polarized modes. This is because the penetration depths of the evanescent wave fields corresponding to the two modes are different, thereby causing the modes propagating through the waveguide to undergo different amounts of phase shift. The fluid sample on the waveguide surface is therefore detected and its properties are measured by measuring differences in the phase shifts, ΔΦ, for the two orthogonal modes. 
     Although this optical technique has been successfully used for detecting chemical and biological substances and measuring related physical properties, it has some drawbacks. For example, the phase difference of the two orthogonal modes can at best be determined with a resolution of δ(ΔΦ)≦2π/1000, which is generally not good enough for detecting extremely small chemical and biological substances in the fluid sample. Biochemical and environmental factors such as non-specific binding and temperature variation in the fluid sample further limit the resolution of this optical technique. 
     Another optical technique that uses evanescent wave surface detection is disclosed in U.S. Pat. No. 5,262,842 issued Nov. 16, 1993 to Gauglitz et. al. That patent discloses an integrated optical Mach-Zehnder interferometer fabricated on a substrate. The interferometer includes a single mode waveguide structure for bifurcating a beam of light into two separate optical paths, which include a measurement path and a comparison path. The surface of the measurement path can be coated with a chemically sensitive layer and a fluid sample allowed to react with this layer. After propagating through the measurement and the comparison paths, the bifurcated light beams are then recombined. Because the chemically sensitive layer changes the index of refraction of the measurement path, the light beam propagating within the measurement path experiences a phase shift. As a result, interference between the two light beams can be measured in the recombined beam. Significantly, this measured interference is proportional to the quantity of chemical or biological substance in the fluid sample. 
     Although this optical technique including a measurement path and a comparison path has the advantage of effectively canceling out non-specific binding and temperature variation in the fluid sample, it also has drawbacks in that the resolution of the technique is generally insufficient for detecting extremely small chemical and biological substances in the fluid sample. 
     Not only is it desirable to have a MEOMS with high resolution sensors for detecting extremely small chemical and biological substances in fluid samples, but it is also desirable to have a MEOMS with structure that supports the testing of extremely small quantities of fluid samples. One such structure is disclosed in International Publication WO 98/28075 published Jul. 2, 1998 to Imaging Research Inc., St. Catharines, Ontario, Calif. That publication discloses a micro-well plate designed for use in imaging systems for imaging of fluorescent, chemiluminescent, bioluminescent, and colorimetric assays. Specifically, the publication discloses structure for optimizing the optical properties of the micro-wells, which are designed to hold extremely small quantities of fluid sample. 
     International Publication WO 98/46981 published Oct. 22, 1998 to LJL Biosystems, Sunnyvale, Calif., USA, discloses another micro-well plate design that further reduces the quantity of fluid sample required for successful imaging. 
     However, neither International Publication WO 98/28075 nor WO 98/46981 disclose structure for controlling the transfer of extremely small quantities of fluid sample into and out of the micro-wells. We have recognized that a practical MEOMS incorporating high-resolution chemical and biological sensors must include such structure. 
     It would therefore be desirable to have a MEOMS for chemical and biological sensing applications. Such a MEOMS would include high-resolution chemical and biological sensors that are capable of detecting extremely small chemical and biological substances in a fluid sample. It would also be desirable to have a MEOMS for chemical and biological sensing applications that includes structure for holding extremely small quantities of the fluid sample and for controlling the transfer of the fluid sample into and out of the MEOMS. 
     SUMMARY OF THE INVENTION 
     The foregoing drawbacks of the prior art have been overcome by an MEOMS sensing chip according to the present invention. In a preferred embodiment, the MEOMS sensing chip includes a system for optically sensing substances in fluid samples and a system for delivering the fluid samples to the sensing system, wherein the sensing system includes at least one two-branch waveguide and a plurality of ring waveguides, each branch of the two-branch waveguide being used for coupling light energy into one of the plurality of ring waveguides, wherein the delivering system includes a plurality of micro-channels and a plurality of micro-wells, the micro-channels being used for transporting the fluid samples to the micro-wells, each micro-well being aligned with a respective ring waveguide and being used for exposing the fluid sample therein to the respective ring waveguide, and wherein characteristics related to the coupling of the light energy into the plurality of ring waveguides are used for detecting substances in the fluid samples. 
     In another embodiment, a device for optically sensing substances in fluid samples includes a first channel waveguide for coupling light energy into a first ring waveguide, the first ring waveguide having a test sample applied to a surface thereof, a second channel waveguide for coupling light energy into a second ring waveguide, the second ring waveguide having a reference sample applied to a surface thereof; a laser for injecting light into the first and the second channel waveguides; and, at least one detector for measuring the intensities of light coupled out of the first and the second channel waveguides, wherein the intensity measurements are used for sensing substances in the test sample relative to the reference sample. 
     In still another embodiment, a method for optically sensing substances in fluid samples includes exposing a test sample to a first ring waveguide; injecting a light beam into a first channel waveguide, thereby coupling at least a portion of the light beam energy into the first ring waveguide; and, detecting the intensity of a remaining portion of the light beam energy coupled out of the first channel waveguide, wherein the detected energy is indicative of the presence of a substance in the test sample. 
     Other aspects of the invention are disclosed infra. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1A is a perspective view of a MEOMS sensing chip in accordance with the present invention, showing a top surface including a micro-fluidic module in accordance with the present invention; 
     FIG. 1B is a perspective view of the MEOMS sensing chip, showing a bottom surface including an optical sensing chip module in accordance with the present invention; 
     FIG. 2 is a schematic view of the optical sensing chip module in accordance with the present invention; 
     FIG. 3 is a cross sectional view of the MEOMS sensing chip of FIG. 2, taken along line  3 — 3 ; 
     FIG. 4 is a cross sectional view of the micro-fluidic module of FIG. 1A, taken along line  4 — 4 ; 
     FIGS. 5A and 5B are graphical representations of the intensities of light coupled out of the optical sensing chip module with respect to the light frequency; 
     FIG. 6A is a graphical representation of the modulated beam coincident with the resonant frequency of the reference arm and of the corresponding detector output; 
     FIG. 6B is a graphical representation of the modulated beam not coincident with the resonant frequency of the measuring arm and of the corresponding detector output; 
     FIG. 7 is a schematic view of an alternate embodiment of the optical sensing chip module in accordance with the present invention; and 
     FIG. 8 is a plan view of the bottom surface of the MEOMS sensing chip showing an alternate embodiment of the optical sensing chip module in accordance with the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring now to the drawings, which depict preferred devices of the invention, FIGS. 1A and 1B show two perspective views of a micro-machined electrical-optical-mechanical system (MEOMS) sensing chip  100  according to the present invention. FIG. 1A shows a top surface (not numbered) of the MEOMS sensing chip  100  comprising a micro-fluidic module  120 , which includes a plurality of fluidic micro-channels  102  and  103  and associated reactor wells  104  and  105 . The fluidic micro-channels  102  and  103  and the reactor wells  104  and  105  are bulk micro-machined onto a planar silicon substrate  101  a using techniques that are well known to those skilled in this art. 
     In the illustrative embodiment shown in FIG. 1A, the micro-channels  102  and  103  have rectangular or V-shaped cross sections and surface cross sectional areas of about 100 microns. Further, the reactor wells  104  and  105  preferably have cylindrical shapes with volume sizes of 1 mm 3 . 
     The MEOMS sensing chip  100  is useful for performing chemical and biological sensing of extremely small chemical and biological substances in fluid samples (not shown). Accordingly, the reactor wells  104  and  105  function as reservoirs for holding extremely small quantities of the fluid samples, e.g., hundreds of micro-liters, during testing. 
     Further, the fluidic micro-channel  102  includes an inlet channel  107  and an outlet channel  111 . Similarly, the fluidic micro-channel  103  includes an inlet channel  109  and an outlet channel  113 . Accordingly, the inlet channels  107  and  109  function as conduits for transporting the fluid samples to the reactor wells  104  and  105 , respectively, for subsequent testing; and, the outlet channels  111  and  113  function as conduits for transporting the fluid samples out of the reactor wells  104  and  105 , respectively, after testing is completed. The inlet channels  107  and  109  and the outlet channels  111  and  113  may be coupled to a micro-fluidic delivery system module (not shown), which controls the transport of the fluid samples into and out of the reactor wells  104  and  105 . The micro-fluidic delivery system module includes micro-fabricated pumps and fluidic channels, which are structures that are known to those skilled in this art and may therefore be readily assembled. 
     FIG. 1B shows a bottom surface (not numbered) of the MEOMS sensing chip  100  comprising an optical sensing chip module  122  with a two-branch channel waveguide  110 , which includes an input portion  112  coupled to a measurement branch  116  and a reference branch  114 . The input portion  112 , the measurement branch  116 , and the reference branch  114  provide optical paths for beams of light propagating within the optical sensing chip module  122 . 
     In particular, the channel waveguide  110  may have rectangular cross sectional dimensions on the order of several micrometers, typically 2 μm to 3 μm. Further, the path length from the beginning of the input portion  112  to the end of the measurement branch  116  is equal to the path length from the beginning of the input portion  112  to the end of the reference branch  114 . Because the waveguide  110  of the optical sensing chip module  122  is implemented as a channel waveguide, scattering of light beams propagating within the waveguide  110  is minimized, thereby enhancing the sensitivity of the MEOMS sensing chip  100 . 
     The optical sensing chip module  122  also includes identical, passive, ring waveguide resonators  106  and  108 . The structure and operation of passive ring waveguide resonators that may be micro-fabricated-onto planar silicon substrates are described in U.S. Pat. No. 5,872,877. issued Feb. 16, 1999 to Haavisto. 
     In the illustrative embodiment shown in FIGS. 1A and 1B, the ring waveguide resonator  106  functions as a measuring arm, and the ring waveguide resonator  108  functions as a reference arm. Further, a portion (not numbered) of the ring waveguide resonator  106  is aligned with the reactor well  105  and a portion (not numbered) of the ring waveguide resonator  108  is aligned with the reactor well  104 , wherein the ring waveguide resonators  106  and  108  and the reactor wells  105  and  104  are formed on opposed surfaces of the MEOMS sensing chip  100  (see FIG.  1 B). In this way, the fluid sample held in the reactor well  105  is exposed to the ring waveguide resonator  106 , and the fluid sample held in the reactor well  104  is exposed to the ring waveguide resonator  108 . The structure and cooperation of the ring waveguide resonators  106  and  108  and the reactor wells  104  and  105  will be described in further detail below with reference to FIGS. 3 and 4. 
     For the illustrative embodiment shown in FIGS. 1A and 1B, the micro-fluidic module  120  and the optical sensing chip module  122  are fabricated on separate planar silicon substrates  101   a  and  101   b , respectively, which are then aligned and bonded together to form the MEOMS sensing chip  100 . This manner of fabricating the MEOMS sensing chip  100  has advantages in that one process optimized for bulk micro-machining silicon can be used to make the micro-fluidic module  120 ; and, another process optimized, for forming channel waveguides on silicon substrates can be used to make the optical sensing chip module  122 . 
     In an alternative embodiment, the micro-fluidic module  120  and the optical sensing chip module  122  are fabricated monolithically on the same silicon substrate (not shown), with the micro-fluidic module  120  micro-machined onto one side of the substrate and the optical sensing chip module  122  formed on the opposite side of the substrate. This alternative manner of fabricating the MEOMS sensing chip  100  has advantages in that the alignment of the micro-fluidic module  120  and the optical sensing chip module  122 , i.e., the alignment of the ring waveguide resonators  106  and  108  with the reactor wells  104  and  105 , may be precisely performed using photolithography. However, this manner of fabricating the MEOMS sensing chip  100 , e.g., concurrently fabricating the micro-fluidic module  120  and the optical sensing chip module  122  on the same silicon substrate, may result in a fabrication process with a less than optimal number of processing steps. 
     Nevertheless, it should be understood that the methods used for micro-machining the micro-fluidic module  120  onto the silicon substrate  101   a  and forming the optical sensing chip module  122  on the silicon substrate  101   b  are conventional and are therefore not critical to this invention. 
     FIG. 2 shows a schematic view of the optical sensing chip module  122 , which is coupled to a laser  202  and light intensity detectors  204  and  206 . Further, the detectors  204  and  206  are coupled to a processor  208 , which optionally uses a servo  210  for adjusting the frequency of light generated by the laser  202 . In particular, the laser  202  injects a coherent light beam (not shown) into the input portion  112  of the channel waveguide  110 , thereby causing the light beam to propagate as a single mode within the input portion  112 . Any suitable integrated optical element (not shown) may be used for coupling the light beam produced by the laser  202  into the input portion  112  of the channel waveguide  110 . In the preferred embodiment, the laser  202  is a gallium aluminum arsenide diode laser. 
     Further, any suitable integrated optical element (not shown) may be used for bifurcating the light beam propagating within the input portion  112 , thereby defining a pair of respective light beams (not shown) propagating as single modes within the measurement branch  116  and the reference branch  114 . The light beam propagating within the input portion  112  is preferably bifurcated so that the energies of the respective light beams propagating within the measurement and the reference branches  116  and  114  are equal. 
     Moreover, the energy of the light beam propagating within the measurement branch  116  is evanescently coupled into the ring waveguide resonator  106 , thereby causing this light energy to propagate around the ring waveguide resonator  106  in a clockwise manner. Similarly, the energy of the light beam propagating within the reference branch  114  is evanescently coupled into the ring waveguide resonator  108 , thereby causing this light energy to propagate around the ring waveguide resonator  108  in a counter clockwise manner. It should be understood that the directions of propagation of the light energies around the ring waveguide resonators  106  and  108  are not critical to this invention. 
     When the frequency of the light beam propagating within the measurement branch  116  equals the resonant frequency corresponding to the ring waveguide resonator  106 , essentially all of the associated light beam energy will be evanescently coupled into the ring waveguide resonator  106 . This means that the intensity of the light beam coupled out of the measurement branch  116  and detected by the detector  204  will fall to a minimum. Similarly, when the frequency of the light beam propagating within the reference branch  114  equals the resonant frequency corresponding to the ring waveguide resonator  108 , essentially all of the energy associated with this light beam will be evanescently coupled into the ring waveguide resonator  108 . The intensity of the light beam coupled out of the reference branch  114  and detected by the detector  206  will therefore fall to a minimum. Any suitable integrated optical element (not shown) may be used for coupling the light beams out of the measurement and the reference branches  116  and  114  and providing the out-coupled light beams to the detectors  204  and  206 . 
     Generally, the relationship between the intensities, I in  and I out , of a light beam coupled into and out of a channel waveguide, wherein the light beam is evanescently coupled to a ring waveguide resonator with a line width, Γ, and the light frequency, f, is near resonance, f 0 , may be approximated as follows: 
     
       
           I   out   =I   in /[1+4/Γ 2 ( f−f   0 ) 2 ]  (Eq. 1) 
       
     
     In addition, the upper surface of the ring waveguide resonator  106 , which functions as a measuring arm, optionally interfaces with a chemically sensitive layer  201 , which may be any suitable chemically sensitive layer known to those skilled in this art. For example, the chemically sensitive layer  201  may be a known polymer or a known biological substance that reacts with the fluid sample held in the reactor well  105 , thereby changing the index of refraction of the chemically sensitive layer  201 . 
     As mentioned above, the reactor well  105  is part of the micro-fluidic module  120 , which is formed on the top surface of the MEOMS sensing chip  100 . Further, the ring waveguide resonator  106  is part of the optical sensing chip module  122 , which is formed on the bottom surface of the MEOMS sensing chip  100 . Accordingly, the chemically sensitive layer  201  may be applied to the surface (not numbered) of the reactor well  105  that interfaces with the ring waveguide resonator  106 . 
     FIG. 3 shows a cross sectional view of the optical sensing chip module  122  taken along the line  3 — 3  of FIG.  2 . In particular, FIG. 3 shows the portion of the ring waveguide resonator  106  formed on the substrate  101   b  that interfaces with the chemically sensitive layer  201 . 
     Generally, a waveguide used in optical sensing applications must have a refractive index that is greater than the refractive index of the planar substrate on which it is formed. Further, the refractive index difference must be large enough to ensure total internal reflection of light propagating within the waveguide. 
     For this reason, the refractive index of the channel waveguide  110  is greater than the refractive index of the substrate  101   b , thereby ensuring total internal reflection of the light beams propagating within the input portion  112  and the measurement and the reference branches  116  and  114 . Similarly, the refractive indices of the ring waveguide resonators  106  and  108  are greater than the refractive index of the substrate  101   b , thereby ensuring total internal reflection of the light energy propagating around the ring waveguide resonators  106  and  108 . 
     Specifically, FIG. 3 shows the optional chemically sensitive layer  201  with a refractive index, n l , the ring waveguide resonator  106  (also called the measuring arm) with a refractive index, n m , and the substrate  101   b  with a refractive index, n s . Thus, in order to ensure total internal reflection of the light energy propagating around the ring waveguide resonator  106 , n m &gt;n s  and n m &gt;n l . 
     FIG. 4 shows a cross sectional view of the reactor well  105  taken along the line  4 — 4  of FIG.  1 A. The structure of the reactor well  104  is preferably identical to the structure of the reactor well  105  and therefore will not be explicitly shown. The reactor well  105  is preferably bulk micro-machined onto the silicon substrate  101   a  with the asymmetric cross section as shown in FIG.  4 . Alternatively, the reactor well  105  may have either a tubular cross section (see FIG. 1 a ) or a polygonal cross section (not shown). It is expected that each of these alternative cross sections will allow maximum circulation of the fluid sample at the bottom of the reactor well  105 . As mentioned above, the reactor wells  104  and  105  preferably have cylindrical shapes with volume sizes of 1 mm 3 . 
     Further, the cladding  402  hermetically seals the reactor well  105  so that no fluid sample (not shown) escapes during testing; and, the cladding  404  bonds the reactor well  105  to the optical sensing chip module  122  so that the fluid sample in the reactor well  105  is evenly exposed to the ring waveguide resonator  106 . All of the inner surfaces (not numbered) of the reactor well  105  are preferably treated to have minimal interaction with chemical or biological substances in the fluid sample. 
     As mentioned above, the fluid sample held in the reactor well  105  reacts with the chemically sensitive layer  201 , thereby changing the refractive index, n l , of the chemically sensitive layer  201 . Further, the light energy propagating around the ring waveguide resonator  106  causes an evanescent wave field  302  to be produced that reaches out into the chemically sensitive layer  201 . This causes the refractive index, n m , and the resonant frequency, f m0 , of the ring waveguide resonator  106  (also called the measuring arm) to change. 
     Similarly, the fluid sample held in the reactor well  104  and exposed to the ring waveguide resonator  108  causes the refractive index, n r , and the resonant frequency, f r0 , of the ring waveguide resonator  108  (also called the reference arm) to change. Further, because the refractive indices, n m  and n r , change, the light beams propagating through the ring waveguide resonators  106  and  108  undergo phase shifts. As a result, chemical and biological substances in the fluid samples held in the reactor wells  104  and  105  can be detected by the detectors  204  and  206  by measuring relative changes in the resonant frequencies, f m0  and f r0 , of the ring waveguide resonators  106  and  108 . 
     The operation of the MEOMS sensing chip  100  will now be described in accordance with the following illustrative example. First, the micro-fluidic delivery system (not shown) transports fluid samples (not shown) through the inlet channels  107  and  109  to the reactor wells  104  and  105 , respectively. It is assumed that the fluid samples held in the reactor wells  104  and  105  include the same types of chemical or biological substances; however, the quantities of the substances in the fluid samples may or may not be the same. Further, it is assumed in this example that the surfaces of the measuring arm, i.e., the ring waveguide resonator  106 , and the reference arm, i.e. the ring waveguide resonator  108 , do not interface with the chemically sensitive layer  201 . Accordingly, in this illustrative example, the MEOMS sensing chip  100  will be used for performing differential measurements of the chemical or biological substances in the fluid samples exposed to the ring waveguide resonators  106  and  108 . 
     Next, the laser  202  injects a coherent light beam into the input portion  112  of the channel waveguide  110 , thereby preferably causing the coherent light beam to propagate as a single mode within the channel waveguide  110 . This is because it is desired that essentially all of the light energy associated with the coherent light beam be evanescently coupled into the ring waveguide resonators  106  and  108  when the light frequency equals the resonant frequencies, f m0  and f r0 . If the coherent light beam were to propagate within the channel waveguide  110  as more than one mode, then it is expected that not all of the light energy associated with all of the modes will be evanescently coupled into the ring waveguide resonators  106  and  108  at resonance. 
     As mentioned above, the channel waveguide  110  is fabricated so that approximately 50% of the light energy of the injected light beam propagates within the measurement branch  116  and the remaining 50% of the light energy propagates within the reference branch  114 . Further, the light beam propagating within the measurement branch  116  is evanescently coupled into the ring waveguide resonator  106 , thereby causing light energy to propagate around the ring waveguide resonator  106  in a clockwise manner. Similarly, the light beam propagating within the reference branch  114  is evanescently coupled into the ring waveguide resonator  108 , thereby causing light energy to propagate around the ring waveguide resonator  108  in a counter clockwise manner. At the resonant frequencies, f m0  and f r0 , of the ring waveguide resonators  106  and  108 , the intensities, I m0  and I r0 , of the light beams coupled out of the measurement and the reference branches  116  and  114  will fall to minimum values. 
     In this illustrative example, the input current to the laser  202 , which is preferably a laser diode, is varied by a ramp signal produced by the servo  210 , thereby causing the light frequency of the injected light beam to sweep through a range of frequencies sufficiently wide enough to encompass the resonant frequencies, f m0  and f r0 , of the ring waveguide resonators  106  and  108 . This approach is especially useful when the phase shift induced in the light energy propagating around the ring waveguide resonators  106  and  108  is large; e.g., from 0.1π to 2π radians. 
     For example, FIG. 5A shows the intensity, I m0 , of the light beam coupled out of the measurement branch  116  and provided to the detector  204 , versus the swept light frequency, f, of the injected light beam. Further, the fluid sample exposed to the ring waveguide resonator  106  causes the resonant frequency of the measuring arm to be equal to f m0 . Accordingly, the intensity, I m0 , falls to a minimum at the frequency, f m0 , because essentially all of the light energy of the light beam propagating through the measurement branch  116  is evanescently coupled into the ring waveguide resonator  106 . 
     Similarly, FIG. 5B shows the intensity, I r0 , of the light beam coupled out of the reference branch  114  and provided to the detector  206 , versus the swept light frequency, f, of the injected light beam. Further, the fluid sample exposed to the ring waveguide resonator  108  causes the resonant frequency of the reference arm to be equal to f r0 . Accordingly, the intensity, I r0 , falls to a minimum at the frequency, f r0 , because essentially all of the light energy of the light beam propagating through the reference branch  114  is evanescently coupled into the ring waveguide resonator  108 . 
     As a result, a differential measurement of the chemical and biological substances in the fluid samples exposed to the ring waveguide resonators  106  and  108  can be made by comparing the relative resonant frequencies, f m0  and f r0 , of the ring waveguide resonators  106  and  108 . 
     When the phase shift induced in the light energy propagating around the ring waveguide resonators  106  and  108  is small, e.g., on the order of 10 −5 π radians, then a different detection approach is useful. Specifically, the processor  208  monitors the intensity, I r0 , of the light detected by the detector  206  and uses the servo  210  to set the input current of the laser  202  so that the frequency of the light energy produced by the laser  202  is at the resonant frequency, f r0 , of the ring waveguide resonator  108 . Next, the induced phase shift is determined using synchronous modulation/demodulation. 
     For example, FIG. 6A shows that when the light frequency  602  of the laser  202  is coincident with the resonant frequency  604 , i.e., ω r0 =2πf r0 , of the ring waveguide resonator  108 , the modulation is centered on the minimum of the resonance dip. The output signal  606  of the detector  206  due to the modulation across the resonant frequency  604  is therefore a pure sinusoid at twice the modulation frequency, which for this example is equal to 20 kHz. Accordingly, when the processor  208  demodulates the output signal  606  at the modulation frequency, zero signal results. 
     Further, FIG. 6B shows that when the light frequency  602  is offset from the resonant frequency  610 , i.e., ω m0 =2f m0 , of the ring waveguide resonator  106 , the output signal  612  from the detector  204  picks up oscillations at the modulation frequency. Accordingly, when the processor  208  demodulates the output signal  612  at the modulation frequency, a dc signal results. As a result, a differential measurement of the chemical and biological substances in the fluid samples exposed to the ring waveguide resonators  106  and  108  can be made by determining the magnitude of the resulting dc signal. 
     Having described one embodiment, numerous alternative embodiments or variations might be made. For example, it was described that the MEOMS sensing chip includes a plurality of ring waveguide resonators, each ring waveguide resonator having a respective reactor well aligned with a portion thereof. However, this was merely an illustration. The MEOMS sensing chip may alternatively include a reactor well that is large enough to be aligned with portions of both the ring waveguide resonator comprising the measuring arm and the ring waveguide resonator comprising the reference arm. This structure is particularly useful for eliminating the effects of biochemical and environmental factors such as non-specific binding and temperature variation in the fluid sample held in the large reactor well. 
     For example, the surface of the measuring arm may interface with a chemically sensitive layer, thereby allowing it to respond to both specific and non-specific interactions in the fluid sample. Further, because the surface of the reference arm does not interface with the chemically sensitive layer, the reference arm will respond to only non-specific interactions in the fluid sample. As a result, all non-specific interactions are concealed by differentiating the outputs of the measuring and the reference arms, thereby allowing the MEOMS sensing chip to detect only specific binding in the fluid sample. 
     It was also described that the MEOMS sensing chip includes a two-branch channel waveguide. However, this was also merely an illustration. FIG. 7 shows that the MEOMS sensing chip may alternatively include a laser  702  that injects a light beam into a channel waveguide  716 . The light beam is evanescently coupled into both the ring waveguide resonator  706  (the measuring arm) and the ring waveguide resonator  708  (the reference arm), thereby causing light energy to propagate around the ring waveguide resonators  706  and  708  in a clockwise manner. The light energies in the ring waveguide resonators  706  and  708  are then evanescently coupled into the channel waveguide  714 . If the laser  702  is controlled for sweeping the light frequency of the injected beam through a range of frequencies sufficiently wide enough to encompass the resonant-frequencies of the ring waveguide resonators  706  and  708 , then the detectors  704  and  706  can be used for determining these resonant frequency values. As a result, a differential measurement of the chemical and biological substances in the fluid samples exposed to the ring waveguide resonators  706  and  708  can be made by comparing the relative resonant frequencies, f m0 , and f r0 , of the ring waveguide resonators  706  and  708 . 
     In addition, FIG. 8 shows an alternative optical sensing chip module  822  with an array of two-branch waveguides  810   a ,  810   b ,  810   c , and  810   d , each having corresponding measuring arms  806 , reference arms  808 , and lasers  802   a ,  802   b ,  802   c , and  802   d.    
     Because fluid samples in reactor wells (not shown) aligned with the measuring arms  806  react independently with chemically sensitive layers (not shown) interfacing with portions of the measuring arms  806 , the optical sensing chip module  822  can be used for performing simultaneous detection and measurement of a plurality of chemical and biological substances in fluid samples. 
     It was also described that each micro-channel includes an inlet channel and an outlet channel for transporting fluid samples into and out of a respective reactor well. However, this was merely an illustration. Inlet channels of a plurality of micro-channels may alternatively merge together for mixing a plurality of samples and then transporting the mixed samples to a reactor well. 
     All documents mentioned herein are specifically incorporated herein by reference. 
     The invention has been described in detail, including the preferred embodiments thereof. However, it will be appreciated that those skilled in the art, upon consideration of the present disclosure, may make modification and/or improvements of this invention and will be within the scope and spirit of the invention as set forth in the following claims.