Abstract:
An integrated optical chip device for molecular diagnostics comprising a tunable laser cavity sensor chip using heterodyned detection at the juncture of a sensor laser and a reference laser, the sensor laser including exposed evanescent field material.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of United States Provisional Patent Application Ser. No. 60/213.608, filed Jun. 20, 2000 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with Government Support under Grant No. N00014-96-1-G014, awarded by the Office of Naval Research. The Government has certain rights in this invention. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to laser sensors using heterodyned laser light. 
     BACKGROUND OF THE INVENTION 
     In recent years, lasers have been put to use in molecular diagnostics. Robert Frankel et al. U.S. Pat. No. 5,637,458 (the disclosure of which is incorporated herein by reference) describes a system for biomolecular separation and detection of a molecular species that uses a solid state laser detector formed with a sample channel. The presence of a molecular species is indicated by a frequency shift in the laser&#39;s output which is detected by optical heterodyning the laser&#39;s output with the output of a reference laser. The interior of the sample channel can, optionally, be coated with a ligand for binding a molecular species of interest. The system involves rather complex preprocessing of the sample by electro-osmotic separation in channels that are lithographically formed in a two dimensional planar substrate and/or by a nanostructural molecular sieve formed of spaced apart posts defining narrow channels. Although an at tempt at integrated system is provided by U.S. Pat. No. 5,637,458, it does not entirely provide a fully integrated optical chip device. 
     Also recently, highly coherent semiconductor lasers and laser arrays have been developed primarily for telecommunications applications. See for example C. E. Zah et al., IEEE Photon. Technol. Lett., vol. 8, pp 864-866, July, 1996. In addition, widely tunable semiconductor lasers have been developed, in particular, sampled-grating distributed Bagg reflector (SGDBR) lasers. See, for example “Tunable Sampled-Grading DBR Lasers with Integrated Wavelength Monitors,” by B. Mason et al.,  IEEE Photonics Technology Letters , Vol. 10, No. 8 August 1998; 1085-1087 and “Ridge Waveguide Sampled Grating DBR Lasers with 22-nm Quasi-Continuous Tuning Range,” by B. Mason et al.,  IEEE Photonics Technology Letters , Vol. 10, No. 9 September 1998, 1211-1213. These widely tunable lasers are based on the use of two multi-element mirrors as described in Coldren U.S. Pat. No. 4,896,325. The former also includes a Y-branch splitter with a detector in each branch for wavelength determination. Disclosures of the foregoing three publications and Coldren U.S. Pat. No. 4,896,325 are incorporated herein by reference. 
     SUMMARY OF THE INVENTION 
     The present invention provides an optical chip device usable for molecular diagnostics, what I call a tunable laser cavity sensor (TLCS). The TLCS is formed from a reference laser and a sensor laser, each comprising a waveguide having a gain section, a partially transmissive mirror section, and a coherent light beam output section, one or both of the waveguides having a phase control section. The light beam output sections of the reference and sensor lasers are joined to enable the coherent light from these sections to interfere, providing a heterodyned frequency. The sensor laser has a thinned waveguide region exposing evanescent field material to form a cavity and which detects the presence of a molecule by a heterodyned frequency shift. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a top plan schematic view of a heterodyned tunable reference and sensor lasers with an intracavity sensor region; 
     FIG. 2 is a bottom perspective view showing the tunable laser cavity sensor with control electrodes for gain, phase, and mirror currents; 
     FIG. 3 is a top plan schematic view of a one-dimensional tunable laser cavity sensor array composed of multiple heterodyne tunable lasers with intracavity interaction regions; 
     FIG. 4 is a cross-sectional, schematic view of a ridge waveguide usable in the present invention; 
     FIG. 5 is a cross sectional perspective view of reference and sensor ridge waveguides; 
     FIG. 6 is a cross sectional schematic view of a buried rib waveguide usable in the present invention; 
     FIG. 7 is a cross sectional perspective schematic view of reference and sensor buried-rib waveguides; 
     FIG. 8 is a schematic plan view of the tunable laser cavity sensor of FIG. 2; and 
     FIG. 9 is a schematic plan view of t tunable laser cavity sensor similar to that of FIG. 8, but with left and right side sampled-grating mirrors. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The tunable laser cavity sensor (TLCS) optical sensor of this invention is shown in top plan view schematically in FIG.  1 . Two distributed-bragg reflector (DBR) tunable lasers  10  and  12  are integrated with a Y-branch coupler  14  and a photodetector  16 . One of the DBR tunable lasers  10  is a reference laser, the other  12  being a sensor laser. The photodetector  16  provides heterodyne detection of small changes in amplitude or frequency of the sensor laser  12  relative to the reference laser  10 . As is known, the frequencies of the reference and sensor lasers can be set, as indicated at  18  and  20  by adjustment of the control sections, more particularly by adjustment of the respective gain  22 ,  24  and phase  26 ,  28  sections of the waveguides. Each waveguide has a partially transmissive grating mirror section  30  and  32  and a coherent light beam output section  34  and  36  which are joined at the mixer detector section  16 . 
     In the illustrated embodiment, the interactive region  40  of the sensor waveguide is formed between the gain and phase control sections, respectively  24  and  28 , and the sampled-grating mirror section  32 . However, the particular order of the components between the mirrors is not critical and other configurations are equally useable. Thus all permutations of the locations of the gain section  24 , phase control section  28  and interactive region  40  can be used. For example, the order from the cleaved facet  12  (FIG. 2) can be phase control section  32 , gain section  28  and interactive region  40 , etc. Also, while a phase control section is shown on both the reference laser  10  and sensor laser  12  it is sufficient to have it on only one of the lasers in order to tune one to the other. As indicated, the left ends of the lasers  10  and  12  are formed by cleaved facets. As described below, both the left-end facet mirrors and the right-side grating mirrors can be sampled-grating mirrors to provide for wider tunability of the lasers output wavelength, in which case, the opposed sampled-grating mirrors would preferably have different sampling periods. Using lasers with different sampled grating periods is described in the aforementioned Coldren U.S. Pat. No. 4,896,325. 
     As shown, the frequency output of the sensor waveguide differs by ±Δλ from the frequency of their reference waveguide. By adjusting the tuning electrodes as shown in FIG. 1, one can enhance the measurement resolution by tuning to possible molecular bond resonances, e.g. in the 1550 nm wavelength range. Researchers at the University of California in Santa Barbara have pioneered DBR lasers with extended tuning ranges-so called sampled-grating-DBR lasers. The lasing wavelengths of these lasers can be tuned up to 100 nm, enabling the measurement of the index of the perturbing species versus wavelength over a relatively wide range to better identify their chemical nature. 
     Referring to FIG. 2, the TLCS is shown in more detail. The tunable cavity sensor is fabricated by integrating a tunable DBR sensor laser  10  with a reference laser  12  and combining them into a heterodyning detector  16  to accurately monitor changes in the modal index or loss due to adsorbates or interactions at the surface of a thinned interaction region  40  on the sensor laser  10 . The InP chip  42  is formed with reference and sensor lasers  10  and  12 , as will be described in more detail hereinafter, each of which carries gain control electrodes, respectively,  44 ,  46  and phase control electrodes, respectively,  54 ,  56  spaced from mirror control electrodes, respectively,  48 ,  50  overlying a partially transmissive grating mirror  56 . 
     FIGS. 8 and 9 show schematic plan views of TLCSs using either a simple DBR partially transmissive mirror or two SGDBRs, respectively. The TLCS of FIG. 8 is that of FIG. 2 shown in plan view, with corresponding lead lines. In the TLCS of FIG. 9, the SGDBR configuration replaces the simple grating on the right side as well as the opposite laser facet mirror with sampled-grating mirrors, respectively  57  and  59 , for extended tuning range. 
     As described with respect to FIG. 1, the reference and sensor coherent light beam output sections  52  and  65  join to deliver interfering light beams at the detector  16 , sensed at a detector electrode  62  thereon. Although a “Y-branch” waveguide combiner element  58  &amp;  60  is shown, another type of waveguide combiner, such as a “Multimode-interference” element may also be employed as is well known to those skilled in the art. The cladding of the sensor laser waveguide  12  is thinned to form the sensor cavity  40  to expose the evanescent fields of the lasing mode, and provide an interaction region. As in Frankel et al., U.S. Pat. No. 5,637,458, the surface of the cavity  40  can be coated with any of various ligands for binding the molecular species of interest, wherein a particular reaction occurs on the surface, or an antigen binds to an antibody adsorbate on the surface, a change in index of refraction, Δn s , will occur at the region just above the surface. Since a portion of the laser mode, Γ xy , fills this transverse region, the modal index is changed by an amount, Γ xy Δn s ,. Also, the interaction region extends along the axis of the laser to fill an axial fraction Γ z , of the cavity, so that the net fill-factor for region in which the perturbation takes place is Γ xy  Γ z . 
     Since the lasing wavelength changes in direct proportion to the net weighted change in index (and frequency as the direct negative), the relative change in laser output wavelength, λ, (or frequency, f) is given by:          Δλ   λ     =         Γ   xy          Γ   z            Δ                   n   s         n   _         =     -       Δ                 f     f                                
     For a typical sensing configuration, Δn s ,=0.1, and Γ xy  Γ z ,=0.01, and assuming the average index of the laser cavity is n=3.3, then Δλ=0.05 nm, or Δf=−6 GHz@λ=1550 nm. Now, if this deviation were to be measured in the optical domain, a quarter-meter or larger spectrometer would be necessary to obtain sufficient resolution to see the effect, which would be very difficult at the chip level. However, with the heterodyne detector of the TLCS of this invention, the shifted optical frequency can be down converted to the VHF radio frequency range where simple frequency counters can be used to measure the difference frequency with 1 Hz accuracy. Using heterodyne detection with two semiconductor lasers, a 6 GHz frequency shift can be measured with an accuracy of about 10 MHz, because this is the approximate linewidth of such lasers. 
     Put another way, again assuming the index shift in the small perturbation region, Δn s =0.1, the net fill-factor of this region relative to the volume of the guided mode can be as small as Γ xy  Γ z ,=(10 MHz)(3.3)/(0.1)(193 THz)=1.7×10 6  Then, for example, if the transverse over lap, Γ xy , is only 0.1% (very conservative estimate of the evanescent field), the axial Γ z , can be as small as 0.17%. Therefore, with a net laser cavity length of 500 μm, single submicron particles can be detected. 
     The relative frequency change, Δf/Δf, of the laser is just equal to the relative modal index change times a fill factor, ΓΔn/n, and this frequency change, Δf, can be measured very accurately in the radio frequency (RF) range after down conversion by mixing with the unperturbed laser in the heterodyne detector, to measure changes in modal index of refraction inside the sensor laser cavity  48  with a resolution estimated at, Δf/f=10 MHz/200 THz≠10 −7 . 
     In many situations it may be desired to detect more than one kind of molecular species. This may be possible by sweeping the wavelengths of the reference and sensor lasers by applying suitable currents to the control electrodes and observing characteristic resonances in the index measurement vs. λ. The use of a widely-tunable laser such as a sampled-grating DBR will facilitate this option. 
     Another approach to detect a multiplicity of species is to use one-dimensional TLCS array on the same chip, as illustrated in FIG. 3. A plurality of TLCSs which can be a dozen or more, but of which only three TLCSs  64 ,  66  and  68  are shown. The TLCSs form an array with successive interactive regions  70 ,  72  and  74 , whereby fluid flows serially from the first interactive region  98  to the last interactive region  74 , as shown by the arrow  76 . 
     Each sensor cavity could measure a different molecular species. The practical number of TLCS array elements and thus sensed molecular species, is mainly limited by the desired to finite chip size. The active elements, including the two DBR lasers are spaced, e.g., by about 500 μm so as to allow space for contacts and to avoid cross talk. Again, spectral index information can also supplement the index information at each element if the wavelengths are varied across some range. 
     In fabricating the TLCS chip, known InP growth and fabrication procedures and DBR laser fabrication characterization procedures can be used. Existing 3-D beam propagation modeling (BPM) software can be utilized to provide inclusion of lateral and transverse variations in straight guides, such as in the interaction region, as well as the actual variations in bends, such as in the Y-branches, offset regions for gain, and detector circuitry, as shown in FIG. 2, will be used. 
     Referring to FIGS. 4 and 5, after a first growth, the lower band gap gain/detector layers are removed in the passive sections and the grating lines are etched into the underlying passive guide in the grating mirror section. In FIG. 4, a transverse cross section of a ridge waveguide is shown. The InGaAsP waveguide  78  is formed on an n-InP buffer and substrate  80 . A p-InP ridge waveguide  82  is formed on the InGaAsP waveguide (regrowth) to provide the top cladding and contact layers, the latter formed by InGaAs. Sampled-grating lasers can be made with the same procedure. See, for example, Mason et al. (1998). 
     Referring to FIG. 5, to form the sensor cavity  48  containing the interaction region, the cladding over the optical waveguide is thinned to expose the vertical evanescent optical field. This results in a much smaller ridge height over the center of the guide but some lateral ridge structure must remain to provide lateral waveguiding. The resultant TLCS with its reference waveguide  82  and sensor waveguide  84  are thus formed. Inert polymer  86  is left at the corners of the ridge guides  82  and  84  to eliminate interactions with the fluid, which is especially important for the reference laser which is not to be affected by the fluid. 
     Referring to FIGS. 6 and 7, in another embodiment of the invention, the waveguides can be buried-rib waveguides formed by etching away all the layers outside of the desired optical channel. As shown in FIG. 6, the n-InP substrate  99  carries a waveguide  90  and adjacent quantum well  94  in a p-InP layer contained in an implanted region  92  under a SiNx layer  96 , an InGaAs contact layer  198  and Ti/Pt/Au contact layer  100  providing electrical contact. 
     As shown in FIG. 7, for the buried-rib embodiment, thinning results in a uniform lateral surface  102 , obtained by removing the passive waveguide layer beneath the surface. The result is a TLCS  104  containing reference and sensor waveguides  106  and  108  with the sensor cavity  110  defining the interactive region of the TLCS. 
     While the invention has been described in terms of specific embodiments, various modifications can be made without departing from the scope of the invention.