Diode laser-based chemical and biological sensor

• US 5,766,956 A
• Filed: 05/27/1997
• Issued: 06/16/1998
• Est. Priority Date: 05/27/1997
• Status: Expired due to Term

• Current Assignee: American Research Corporation Of Virginia
• Original Assignee: American Research Corporation Of Virginia
• Inventors: Luo, Shu-Fang, Lo, K. Peter, Groger, Howard P., Churchill, Russell J.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US08/862,929
• Time in Patent Office: 385 Days
• Field of Search: 422/82.05, 422/82.08, 422/82.07, 422/82.09, 422/82.11, 356/318, 436/164, 436/172, 436/524-527
• US Class Current: 436/164
• CPC Class Codes: G01N 2021/391 Intracavity sample
• CPC Class Codes: G01N 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: G01N 2201/0612 Laser diodes

Abstract

A-compact, diode laser-based sensor has applications in biological and chemical analysis. Unlike existing optical waveguide-based sensors, no external coupling to external optical fibers or waveguides is required to perform optical chemical, immunological or nucleic acid-based assay or to detect the presence of toxic or otherwise important chemicals. The sensor includes a surface-sensitive diode laser having a substrate layer, an n-contact layer positioned on a bottom surface of the substrate, an n-clad layer overlying the top surface of the substrate, a first guide layer overlying the n-clad layer, a quantum well layer overlying the first guide layer, a second guide layer overlying the first quantum well layer, a p-clad layer overlying the second guided layer and a p-doped cap layer overlying the p-clad layer. A pair of electrodes separated by a surface-sensitive region is positioned on the cap layer. The surface active region includes an oxide layer grown on the thick cap layer and an absorbing or non-absorbing film deposited on the oxide layer. For internal reflection, inorganic material coatings are applied to end facets or Bragg reflectors are etched in the cap layer. Detectors are positioned proximate the diode laser for detecting changes in film thickness or refractive index, absorption or other optical properties resulting from film deposition, surface reactions such as immunological or ion-exchange reactions, or other detectable processes.

Claims

1. A surface-sensitive diode laser sensor apparatus comprising a substrate having a bottom surface and a top surface, a diode laser grown on the top surface of the substrate, and a detector positioned proximate the diode laser or included in an internal structure of the diode laser, wherein the diode laser further comprises a lasing structure positioned on the top surface of the substrate, a cap layer positioned on the lasing structure, a segmented electrode positioned on the cap layer, wherein the segmented electrode further comprises a first electrode and a second electrode separated by a surface-sensitive region, and wherein the surface-sensitive region further comprises a sensitive coating prepared on the cap layer in the surface-sensitive region.

2. The apparatus of claim 1, wherein the lasing structure further comprises a lower laser region positioned on the upper surface of the substrate, an upper laser region and a quantum well sandwiched between the upper laser region and the lower laser region.

3. The apparatus of claim 2, wherein the lower laser region further comprises an n-cladding layer positioned on the upper surface of the substrate and an n-guide layer overlying the n-cladding layer, and wherein the upper laser region further comprises a p-guide layer positioned on the quantum well and a p-cladding layer overlying the p-guide layer.

4. The apparatus of claim 3, wherein the cladding and guide layers are aluminum gallium arsenide layers.

5. The apparatus of claim 2, wherein the quantum well further comprises a central layer sandwiched between a pair of undoped GaAs layers.

6. The apparatus of claim 5, wherein the central layer comprises gallium indium phosphide and wherein the undoped layers are gallium arsenide layers.

7. The apparatus of claim 1, further comprising a p-layer positioned between the cap layer and the lasing structure.

8. The apparatus of claim 1, wherein the cap layer is a gallium arsenide layer having p-conductivity.

9. The apparatus of claim 1, wherein the first and second electrodes are gold electrodes.

10. The apparatus of claim 1, further comprising a contact layer positioned on the bottom surface of the substrate and wherein the contact layer is a n-type Ge/Au/Ni contact layer.

11. The apparatus of claim 1, wherein the substrate is a doped n-type gallium arsenide substrate.

12. The apparatus of claim 1, wherein end facets are defined by side edges of the diode laser, and further comprising an inorganic chemical coating applied to the end facets for passivating the end facets.

13. The apparatus of claim 1, wherein upper surface of the cap layer outside of the surface sensitive region further comprises a grating surface having surface corrugations.

14. The apparatus of claim 13, wherein the grating surface further comprises Bragg grating reflectors.

15. The apparatus of claim 1, further comprising a coupling layer positioned between the sensitive coating and the cap layer.

16. The apparatus of claim 15, wherein the coupling layer is an oxide layer.

17. The apparatus of claim 1, wherein the sensitive coating further comprises an absorbing dye or a fluorescent dye immobilized in a polymer or ceramic material.

18. The apparatus of claim 17, wherein the dye is selected from the group consisting of 4-(2-(2-chloro-3-((2,6 diphenyl-4H-thiopyran-4-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-2,6 diphenylthiopyrylium tetrafluoroborate in a Nafion binder, 1-Butyl-2-(2-(3-((1-butyl-6-clorobenz(cd)indol-2(1H)-ylidene)ethylidene)-2-chloro-1-cyclohexen-1-yl)ethenyl)-6-chlorobenz(cd) indolium tetrafluorborate in a Nafion binder, 4-(2-(2-chloro-3-((2,6 diphenyl-4H-thiopyran-4-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-2,6 diphenylthiopyrylium tetrafluoroborate having an attached pendant isothiocyanato functional group, 1-Butyl-2(2-(3-((1-butyl-6-clorobenz(cd)indol-2(1H)-ylidene)ethylidene)-2-chloro-1-cyclohexen-1-yl)ethenyl)-6-chlorobenz(cd) indolium tetrafluorborate having an attached pendant isothiocyanato functional group, napthalocyanine dyes, and napthalocyanine dyes having Vanadium metal centers.

19. The apparatus of claim 1, wherein the sensitive coating further comprises non-absorbing materials selected from the group consisting of antibody materials and nucleic acid materials of a known sequence.

20. The apparatus of claim 1, wherein the detector is a wavelength-sensitive detector for measuring an optical output of the lasing structure.

21. The apparatus of claim 20, wherein the wavelength-sensitive detector is selected from the group consisting of grating-based spectrograph, a Fizeau interferometer, a Fourier transform interferometer or any other wavelength sensitive interferometer, and a grating in combination with an array detector.

22. The apparatus of claim 1, wherein the detector monitors changes in electrical characteristics.

23. The apparatus of claim 22, wherein the detector further comprises a pulse generator for developing pulse signals at a constant repetition rate and for delivering the pulse signals through a micropositioner to the lasing structure of the diode laser, a photodiode for receiving emitted laser signals from the lasing structure and for converting the laser signals to electrical signals, and gated electronics for comparing the electrical signals to the pulse signals from the pulse generator for detecting and identifying chemicals.

24. An optical sensor apparatus comprising a substrate having a top surface and a bottom surface, at least two diode lasers grown on the top surface of the substrate, wherein at least one of the diode lasers is a sampling laser and wherein at least one of the lasers is a referencing laser, and a detector for detecting outputs from the lasers, wherein each diode laser further comprises an n-clad layer positioned on the top surface of the substrate, a first guide layer overlying the n-clad layer, a quantum well overlying the first guide layer, a second guide layer overlying the quantum well, a p-clad layer overlying the second guide layer, a cap layer positioned on the p-clad layer and a segmented electrode positioned on the cap layer, wherein the segmented electrode further comprises a first electrode and a second electrode separated by a surface-sensitive region, wherein the surface-sensitive region further comprises a sensitive coating prepared on the cap layer in the surface-sensitive region, wherein the thickness of the cap layer of the at least one sampling laser in the surface-sensitive region is optimal for surface sensitivity, and further comprising a blocking layer positioned on the cap layer of the at least one referencing laser for removing referencing laser sensitivity.

25. The apparatus of claim 24, wherein upper surfaces of the cap layers of the diode lasers outside of the surface-sensitive regions have surface corrugations.

26. The apparatus of claim 24, wherein each diode laser has a laser generation region positioned beneath the electrodes and a laser detection region positioned at a far end of the laser, wherein the cap layer of each diode laser is discontinuous between the laser detection region and the laser generation region, and further comprising electrodes positioned on the cap layers overlying the laser detection region of the diode lasers for detecting and monitoring laser output.

27. A method for detecting trace levels of gases, biological compounds or biochemical materials in solution or in air comprising the steps of providing a surface-sensitive diode laser sensor, exposing a surface-sensitive region of the sensor to an environment including analytes of interest, and monitoring changes in optical characteristics of the diode laser sensor, wherein the sensor further comprises a substrate having a bottom surface and a top surface, a diode laser grown on the top surface of the substrate, and a detector positioned proximate the diode laser or included in an internal structure of the diode laser, wherein the diode laser further comprises a lasing structure positioned on the top surface of the substrate, a cap layer positioned on the lasing structure, a segmented electrode positioned on the cap layer, wherein the segmented electrode further comprises a first electrode and a second electrode separated by a surface-sensitive region, and wherein the surface-sensitive region further comprises a sensitive coating prepared on the cap layer in the surface-sensitive region.

28. The method of claim 27, wherein the providing step further comprises placing the sensor in a flow cell or chamber, and wherein the exposing step further comprises the step of introducing a flow carrying the analytes of interest into the flow cell or chamber.

29. The method of claim 28, further comprising the steps of delivering a washing flow to the chamber following the monitoring step, removing the washing flow from the chamber and regenerating the sensor without removing the sensor from the chamber, the regenerating step further comprising delivering a flow of sensor regeneration materials to the chamber.

30. The method of claim 27, wherein the sensitive coating further comprises materials selected from the group consisting of absorbing dyes, fluorescent dyes, and non-absorbing materials selected from the group consisting of antibody materials and nucleic acid materials of a known sequence.

31. The method of claim 27, wherein the sensor further comprises multiple diode lasers having surface-sensitive regions deposited on the substrate, and further comprising the step of rendering at least one, but less than all, of the diode lasers insensitive to environmental conditions.

32. The method of claim 31, wherein the rendering step further comprises blocking the surface-sensitive region of the lasers.

33. A biosensor instrument system comprising a surface-sensitive diode laser-based sensor positioned in a flow cell, a supply line connected to the inlet side of the flow cell, a specimen source connected to the supply line, a wash source connected to the supply line, a sensor regeneration material source connected to the supply line, an effluent line extending from the exit side of the chamber, a pump positioned in the effluent line, and control and processing electronics electrically connected to the diode laser sensor for monitoring the surface-sensitive effects resulting from specimen flow, wherein the sensor further comprises a substrate having a bottom surface and a top surface, a diode laser grown on the top surface of the substrate, and a detector positioned proximate the diode laser or included in an internal structure of the diode laser, wherein the diode laser further comprises a lasing structure positioned on the top surface of the substrate, a cap layer positioned on the lasing structure, a segmented electrode positioned on the cap layer, wherein the segmented electrode further comprises a first electrode and a second electrode separated by a surface-sensitive region, and wherein the surface-sensitive region further comprises a sensitive coating prepared on the cap layer in the surface-sensitive region.