Hand-held micro-raman based detection instrument and method of detection

• US 10,253,346 B2
• Filed: 08/07/2014
• Issued: 04/09/2019
• Est. Priority Date: 08/07/2013
• Status: Active Grant

• Current Assignee: Seraph Biosciences, Inc., Wayne State University
• Original Assignee: Seraph Biosciences, Inc., Wayne State University
• Inventors: Auner, Gregory William, Shanley, Charles, Brusatori, Michelle, Twomey, Tara, Sant, David
• Primary Examiner(s): Smith, Maurice
• Application Number:
  US14/910,459
• Publication Number:
  US 20160177366A1
• Time in Patent Office: 1,706 Days
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/445 Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore
• CPC Class Codes: A61B 5/6815 Ear
• CPC Class Codes: A61B 5/6819 Nose
• CPC Class Codes: A61B 5/682 Mouth, e.g., oral cavity; tongue; Lips; Teeth
• CPC Class Codes: A61B 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence
• CPC Class Codes: C12Q 1/14 Streptococcus; Staphylococcus
• CPC Class Codes: G01J 2003/1213 Filters in general, e.g. dichroic, band
• CPC Class Codes: G01J 2003/2826 Multispectral imaging, e.g. filter imaging
• CPC Class Codes: G01J 3/0208 using focussing or collimating elements, e.g. lenses or mirrors; performing aberration correction
• CPC Class Codes: G01J 3/0264 Electrical interface; User interface
• CPC Class Codes: G01J 3/0272 Handheld
• CPC Class Codes: G01J 3/0291 Housings; Spectrometer accessories; Spatial arrangement of elements, e.g. folded path arrangements
• CPC Class Codes: G01J 3/18 using diffraction elements, e.g. grating gratings per se G02B
• CPC Class Codes: G01J 3/2823 Imaging spectrometer
• CPC Class Codes: G01J 3/44 Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01J 3/4412 Scattering spectrometry particle sizing by light scattering G01N15/0205; optical velocimetry of particles G01P5/20, G01P5/26
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 2201/0221 : Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 2333/11 : Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: G01N 2333/31 : from Staphylococcus (G)
• CPC Class Codes: G01N 2333/34 : from Corynebacterium (G)

Abstract

A Raman spectroscopy based system and method for examination and interrogation provides a method for rapid and cost effective screening of various protein-based compounds such as bacteria, virus, drugs, and tissue abnormalities. A hand-held spectroscope includes a laser and optical train for generating a Raman-shifting sample signal, signal processing and identification algorithms for signal conditioning and target detection with combinations of ultra-high resolution micro-filters and an imaging detector array to provide specific analysis of target spectral peaks within discrete spectral bands associated with a target pathogen.

Claims

1. A hand held Raman spectroscopic instrument for pathogen detection comprising:

a housing having a handle portion, a head portion and an end effector, the end effector comprising a disposable speculum that comprises

a base detachably secured to the head portion of the housing and a tip having an aperture formed therethrough, the disposable speculum tapering from the base to the tip; and

a filter located at the aperture, an optical window located near the base, and a port coupled to the end effector for drawing a sample through the filter and onto the optical window by vacuum;

a Raman spectroscopic probe encased in the housing and including;

a laser disposed in the handle portion and operable to emit a coherent light beam;

a laser line filter operable to transmit the light beam along an optical path and suppress ambient light;

a beam splitter disposed in the head portion and operable to reflect the light beam from the laser line filter through the aperture formed in the end effector toward onto a sample to produce a Raman-shifted sample signal;

a collector to collect the sample signal and transmit the sample signal through the beam splitter;

a beam expander to collimate the sample signal from the beam splitter and generate an expanded diameter sample signal;

an ultra-high resolution, narrow range, spatially graded filter to filter the expanded diameter sample signal based on a predetermined set of discrete spectral bands for a target pathogen to isolate at least one narrow spectral band; and

an imager for converting the at least one narrow spectral band to image data representative of the Raman-shifted sample signal; and

an electronics assembly comprising;

a micro-controller for controlling the Raman spectroscopic probe, reading the image data from the imager, analyzing the image data at the discrete spectral bands to detect the presence of the target pathogen, comparing the image data with a baseline Raman spectrum and communicating a test result based on the analysis and comparison; and

a power source operably coupled to the micro-controller and the Raman spectroscopic probe.

2. The detection instrument of claim 1 wherein the filter filters the expanded diameter sample signal in at least one narrow spectral band selected from the group consisting of:

640-740 cm<sup>−

1</sup>, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

3. The detection instrument of claim 1 wherein the ultra-high resolution, narrow range, spatially graded filter comprises a filter divided into discrete regions for simultaneously filtering the expanded diameter sample signal in a plurality of narrow spectral bands, each of said discrete regions filtering the expanded diameter sample signal at one of the plurality of narrow spectral bands based on a predetermined set of discrete spectral bands for a target pathogen to isolate the plurality of narrow spectral bands.

4. The detection instrument of claim 3 wherein the filter filters the expanded diameter sample signal in a plurality of narrow spectral bands selected from the group consisting of:

640-740 cm<sup>−

1</sup>, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

5. The detection instrument of claim 3 wherein the filter filters the expanded diameter sample signal in each of the spectral bands at 640-740 cm⁻

1, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

6. The detection instrument of according to claim 1, wherein the filter is divided into discrete regions, each of said discrete regions providing filtering at one of a plurality of narrow spectral bands selected from the group consisting of:

640-740 cm<sup>−

1</sup>, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

7. The detection instrument according to claim 1, wherein the Raman spectroscopic probe further comprises a 180-degree backscatter element interposed between the beam splitter and the end effector aperture, the backscatter element comprising:

a centrally located collection fiber for transmitting the Raman-shifted sample signal to the beam splitter;

a plurality of excitation fibers radially arranged with respect to the collection fiber for transmitting the coherent light beam; and

a beam-splitting mirror for reflecting the coherent light beam emitted from the plurality of excitation fiber and passing the Raman-shifted sample signal therethrough.

8. The detection instrument according to claim 1, wherein the Raman spectroscopic probe further comprises a laser blocking filter between beam splitter and the detector.

9. The detection instrument of claim 1 wherein the disposable speculum further comprises a lens arranged at the tip in the aperture to focus the light beam and collect the sample signal.

10. A method for detecting a target pathogen using Raman-based spectroscopic analysis comprising:

providing a Raman spectroscopic instrument comprising a housing having a head portion and an end effector, the end effector comprising a disposable speculum that comprises

a base detachably secured to the head portion of the housing and a tip having an aperture formed therethrough, the disposable speculum tapering from the base to the tip; and

a filter located at the aperture, an optical window located near the base, and a port coupled to the end effector for drawing a sample through the filter and onto the optical window by vacuum;

transmitting, by the Raman spectroscopic instrument, a coherent light beam onto a sample to generate a Raman-shifted sample signal;

filtering, by the Raman spectroscopic instrument, the Raman-shifted sample signal to simultaneously isolate a plurality of narrow spectral bands based on a predetermined set of discrete spectral bands for a target pathogen to generate a filtered Raman-shifted sample signal;

generating, by the Raman spectroscopic instrument, image data representative of the filtered Raman-shifted sample signal;

analyzing, by the Raman spectroscopic instrument, the image data at the discrete spectral bands to detect the presence of the target pathogen;

comparing, by the Raman spectroscopic instrument, the image data with a baseline Raman spectrum; and

displaying, by the Raman spectroscopic instrument, a positive result when the comparison of the image data with the baseline Raman spectrum indicates a match.

11. The method for detecting a target pathogen of claim 10 wherein the plurality of narrow spectral bands are selected from the group consisting of:

640-740 cm<sup>−

1</sup>, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

12. The method for detecting a target pathogen of claim 10 wherein the Raman-shifted signal is filtered in each of the narrow spectral bands at 640-740 cm⁻

1, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

13. The method for detecting a target pathogen according to claim 10 further comprising projecting, by the Raman spectroscopic instrument, the coherent light beam through a lens and onto the sample.

14. The method for detecting a target pathogen according to claim 10 further comprising drawing, by the Raman spectroscopic instrument, the sample through the filter and depositing, by the Raman spectroscopic instrument, the filtered sample on the optical window, wherein the coherent light beam is transmitted through the optical window onto the sample.

15. A method for detecting a target pathogen using a hand held spectroscope comprising:

providing the hand held spectroscope comprising a housing having a head portion and an end effector, the end effector comprising a disposable speculum that comprises

a base detachably secured to the head portion of the housing and a tip having an aperture formed therethrough, the disposable speculum tapering from the base to the tip; and

a filter located at the aperture, an optical window located near the base, and a port coupled to the end effector for drawing a sample through the filter and onto the optical window by vacuum;

transmitting, by the hand held spectroscope, a coherent light beam from a laser in the housing along an optical path through the aperture and onto a sample to generate a Raman-shifted sample signal;

receiving, by the hand held spectroscope, the Raman-shifted sample signal through the aperture;

filtering, by the hand held spectroscope, the Raman-shifted sample signal to simultaneously isolate a plurality of narrow spectral bands based on a predetermined set of discrete spectral bands for a target pathogen to generate a filtered Raman-shifted sample signal;

projecting, by the hand held spectroscope, the filtered Raman-shifted sample signal onto an imager in the spectroscope housing to generate image data representative of the filtered Raman-shifted sample signal;

analyzing, by the hand held spectroscope, the image data at the discrete spectral bands to detect the presence of the target pathogen;

comparing, by the hand held spectroscope, the image data with a baseline Raman spectrum; and

displaying, by the hand held spectroscope, a positive result when the comparison of the image data with the baseline Raman spectrum indicates a match.

16. The method for detecting a target pathogen of claim 15 wherein the plurality of narrow spectral bands are selected from the group consisting of:

640-740 cm¹, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.

17. The method for detecting a target pathogen of claim 15 wherein the Raman-shifted signal is filtered in each of the narrow spectral bands at 640-740 cm⁻

1, 1200-1260 cm<sup>−

1</sup>, 1520-1560 cm<sup>−

1</sup>, and 1640-1740 cm<sup>−

1</sup>.