Hand-held micro-raman based detection instrument and method of detection
Inventors
Auner, Gregory William • Shanley, Charles • Brusatori, Michelle • Twomey, Tara • Sant, David
Assignees
SERAPH BIOSCIENCES LLC • Seraph Biosciences Inc • Wayne State University
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Publication Number
US-10253346-B2
Publication Date
2019-04-09
Expiration Date
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.
Core Innovation
The invention provides a hand held Raman spectroscopic instrument for pathogen detection that uses a housing with a handle portion, a head portion and an end effector. The end effector includes a disposable speculum with a base detachably secured to the head portion and a tapered tip having an aperture, with 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 in the housing emits a coherent light beam from a laser and suppresses ambient light using a laser line filter. The beam splitter reflects the light beam through the aperture toward a sample to produce a Raman-shifted sample signal, and a collector transmits the sample signal through the beam splitter. A beam expander generates an expanded diameter sample signal, and an ultra-high resolution narrow range spatially graded filter isolates at least one narrow spectral band from a predetermined set of discrete spectral bands for a target pathogen.
An imager converts the isolated narrow spectral band(s) into image data representative of the Raman-shifted sample signal. A micro-controller reads the image data, analyzes the image data at the discrete spectral bands to detect the presence of the target pathogen, compares the image data with a baseline Raman spectrum, and communicates a test result based on the analysis and comparison. In the method aspect, the instrument transmits the coherent light beam, filters the Raman-shifted sample signal to simultaneously isolate a plurality of narrow spectral bands, generates image data, and displays a positive result when a match is indicated.
Claims Coverage
The independent claims are clm-00001, clm-00010, and clm-00015. Across these, the inventive features center on a hand-held Raman pathogen detection architecture with a vacuum-sampled disposable speculum, Raman-shifted signal generation, filtering into predetermined discrete narrow spectral bands using an ultra-high resolution spatially graded filter, and image-data analysis by comparison to a baseline Raman spectrum to display match/positive results. The independent claims contain a total of three core inventive-feature groupings that vary mainly in apparatus versus method framing and the specific sequence of signal handling and display.
Disposable tapered speculum with vacuum sampling path and optical window
The end effector comprises a disposable speculum with a base detachably secured to the head portion, a tapered tip with an aperture, 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.
Raman-shifted sample signal generation with ambient light suppression and imaging of isolated bands
A Raman spectroscopic probe includes a laser, a laser line filter to suppress ambient light, a beam splitter to reflect the light beam through the aperture to produce a Raman-shifted sample signal, and a beam expander to generate an expanded diameter sample signal, with an imager converting isolated narrow spectral band(s) into image data representative of the Raman-shifted sample signal.
Ultra-high resolution spatially graded filter isolating predetermined discrete narrow spectral bands for a target pathogen
An ultra-high resolution narrow range spatially graded filter filters 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; in the method, the Raman-shifted sample signal is filtered to simultaneously isolate a plurality of narrow spectral bands based on the predetermined set.
Micro-controller image-data analysis with baseline Raman spectrum comparison and positive result display
A micro-controller reads image data from the imager, analyzes the image data at the discrete spectral bands to detect the presence of the target pathogen, compares the image data with a baseline Raman spectrum, and communicates a test result; in the method, a positive result is displayed when the comparison indicates a match.
Method-level filtering into image data at discrete bands for match/positive result
The method transmits a coherent light beam to generate a Raman-shifted sample signal, filters the Raman-shifted sample signal to simultaneously isolate a plurality of narrow spectral bands based on a predetermined set for a target pathogen, generates image data representative of the filtered Raman-shifted sample signal, analyzes the image data at the discrete spectral bands to detect the presence of the target pathogen, compares the image data with a baseline Raman spectrum, and displays a positive result when a match is indicated.
Overall, the independent claims cover a hand-held Raman pathogen detection instrument and methods that use a disposable speculum with vacuum sampling to an optical window, generate Raman-shifted sample signals using ambient-light suppression, isolate predetermined discrete narrow spectral bands using an ultra-high resolution spatially graded filter, and analyze image data with baseline Raman spectrum comparison to detect a target pathogen and display a positive match result.
Stated Advantages
Rapid, cost-effective, near-real-time pathogen identification.
Minimal/no sample prep.
Field deployable.
Adaptable to different targets via learning algorithms.
Documented Applications
Point-of-care detection of protein-based pathogens using reagentless Raman spectral fingerprint analysis.
Detection and identification of staphylococci including separation by genus/strain and feasibility results for separating staphylococci.
Detection of influenza despite confounding background.
Mucosal examination including nares and oral/ear interrogation using disposable end effector/speculum configurations.
Wound interrogation using disposable interrogation tips.
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