# US 11,896,373 B2 · Tunable hybrid III-V/ IV laser sensor system-on-a chip for real-time monitoring of a blood constituent concentration level > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,896,373 B2 - Document ID: US11896373B2 - Status: Granted - Kind: B2 - Application number: 16/609,355 - Filed: 2018-05-21 - Published: 2020-03-05 - Granted: 2024-02-13 - Earliest claimed: 2017-05-22 - Assignees: Brolis Sensor Technology, UAB - Applicants: Brolis Sensor Technology, UAB; Universiteit Gent; Imec Vzw - Inventors: Augustinas Vizbaras; Kristijonas Vizbaras; Ieva Simonyte; Günther Roelkens - Web page: https://patentgrep.com/patent/US11896373B2 ## CPC - A61B 5/1455: using optical sensors, e.g. spectral photometrical oximeters - G01J 3/10: Arrangements of light sources specially adapted for spectrometry or colorimetry - G01J 3/42: Absorption spectrometry; Double beam spectrometry; Flicker spectrometry; Reflection spectrometry (beam switching arrangements G01J3/08) - G01N 21/39: using tunable lasers - H01S 5/1032: {Coupling to elements comprising an optical axis that is not aligned with the optical axis of the active region} - H01S 5/142: {which comprises an additional resonator} - H01S 5/4062: {with an external cavity or using internal filters, e.g. Talbot filters} - A61B 2562/0238: Optical sensor arrangements for performing transmission measurements on body tissue - G01J 2003/423: {Spectral arrangements using lasers, e.g. tunable} - H01S 3/106: by controlling devices placed within the cavity ({H01S3/10076,} H01S3/13 take precedence) - H01S 5/021: {Silicon based substrates} - H01S 5/02326: Arrangements for relative positioning of laser diodes and optical components, e.g. grooves in the mount to fix optical fibres or lenses - H01S 5/0234: Up-side down mountings, e.g. Flip-chip, epi-side down mountings or junction down mountings - H01S 5/026: Monolithically integrated components, e.g. waveguides, monitoring photo-detectors, drivers (stabilisation of output H01S5/06) - H01S 5/0264: {for monitoring the laser-output} - H01S 5/0287: {Facet reflectivity} - H01S 5/0612: {controlled by temperature} - H01S 5/125: Distributed Bragg reflector [DBR] lasers - H01S 5/20: Structure or shape of the semiconductor body to guide the optical wave {; Confining structures perpendicular to the optical axis, e.g. index or gain guiding, stripe geometry, broad area lasers, gain tailoring, transverse or lateral reflectors, special cladding structures, MQW barrier reflection layers} - H01S 5/4012: {Beam combining, e.g. by the use of fibres, gratings, polarisers, prisms} - H01S 5/4087: {emitting more than one wavelength} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - H01S: DEVICES USING THE PROCESS OF LIGHT AMPLIFICATION BY STIMULATED EMISSION OF RADIATION [LASER] TO AMPLIFY OR GENERATE LIGHT; DEVICES USING STIMULATED EMISSION OF ELECTROMAGNETIC RADIATION IN WAVE RANGES OTHER THAN OPTICAL ## Abstract A spectroscopic laser sensor based on hybrid lll-V/IV system-on-a-chip technology. The laser sensor is configured to either (i) be used with a fiber-optic probe connected to an intravenous/intra-arterial optical catheter for direct invasive blood analyte concentration level measurement or (ii) be used to measure blood analyte concentration level non-invasively through an optical interface attached, e.g., to the skin or fingernail bed of a human. The sensor includes a lll-V gain-chip, e.g., an AIGalnAsSb/GaSb based gain-chip, and a photonic integrated circuit, with laser wavelength filtering, laser wavelength tuning, laser wavelength monitoring, laser signal monitoring and signal output sections realized on a chip by combining IV-based semiconductor substrates and flip-chip AIGal-nAsSb/GaSb based photodetectors and embedded electronics for signal processing. Embodiments of the invention may be applied for real-time monitoring of critical blood analyte concentration levels such as lactates, urea, glucose, ammonia, albumin, etc. ## Claims ### Claim 1 A laser-based sensor system-on-a-chip for real-time monitoring of a constituent concentration level in a subject, the system-on-a-chip comprising: a tunable hybrid III-V/IV laser sensor; and a fiber-optic interface coupled to the laser sensor, the interface comprising a probe, wherein during use the laser sensor is remote from the subject and the probe is in optical communication with the subject. ### Claim 2 (depends on 1) A laser-based sensor system-on-a-chip of claim 1, wherein the IV comprises a IV-based semiconductor substrate selected from the group consisting of silicon, silicon-on-insulator, silicon nitride on silicon-on-insulator, germanium-on-insulator, and silicon nitride on silicon. ### Claim 3 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, wherein the tunable laser sensor comprises a III-V gain-chip and a photonic integrated circuit disposed on a IV-based substrate, the photonic integrated circuit (i) being configured to perform wavelength filtering and tuning functions based on Vernier effect and (ii) defining an external cavity for the III-V gain-chip. ### Claim 4 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, wherein the laser sensor comprises at least one III-V photodiode coupled to a photonic integrated circuit by at least one of flip-chip bonding, gluing, transfer printing technology, or side coupling. ### Claim 5 (depends on 4) The laser-based sensor system-on-a-chip of claim 4, where the photonic integrated circuit comprises a signal and wavelength monitoring section. ### Claim 6 (depends on 5) The laser-based sensor system-on-a-chip of claim 5, wherein the signal and wavelength monitoring section comprises (i) at least one of a set of Mach-Zehnder interferometers or coupled ring resonators, and (ii) at least one flip-chip III-V photodiode. ### Claim 7 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, further comprising a discrete III-V photodiode disposed remotely from the tunable laser sensor, wherein, in use, a reflected signal from the subject is collected by the discrete III-V photodiode. ### Claim 8 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, wherein the laser sensor is configured to perform a wavelength sweep across a tuning range as a function of time, and the laser sensor comprises a photodiode configured to convert light reflected from the subject into an electrical signal. ### Claim 9 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, wherein the fiber-optic interface is connected to an optical catheter and is configured to (i) transmit a light signal from the sensor to blood of the subject and (ii) transmit reflected light from the blood of the subject to the sensor. ### Claim 10 (depends on 1) The laser-based sensor system-on-a-chip of claim 1, wherein the fiber optic interface is in optical communication with beam shaping optics configured to non-invasively illuminate a blood sample of the subject through the subject's skin or outer tissue. ### Claim 11 (depends on 1) A sensor comprising an array of cells, each cell comprising a laser-based sensor system-on-a chip of claim 1, wherein each array cell is targeted at a different spectral region and a separate target molecule. ### Claim 12 A method of manufacturing a laser-based sensor system-on-a chip for real-time monitoring of a constituent concentration level in a subject, the method comprising the steps of: manufacturing a tunable hybrid III-V/IV laser sensor by manufacturing a III-V semiconductor gain-chip, fabricating a photonic integrated circuit on a group IV-based semiconductor substrate by CMOS technology to define a group IV semiconductor chip, and hybridly integrating the III-V gain-chip and the group IV semiconductor chip, wherein the photonic integrated circuit is (i) configured to perform wavelength filtering and tuning functions based on Vernier effect and (ii) defines an external cavity for the III-V gain-chip; and coupling a fiber-optic interface to the laser sensor, the interface comprising a probe, wherein during use the laser sensor is remote from the subject and the probe is in optical communication with the subject. ### Claim 13 (depends on 12) The method of claim 12, wherein hybridly integrating the III-V gain-chip and the group IV semiconductor chip comprises edge-coupling the III-V gain-chip to the group IV semiconductor chip, actively aligning the two chips, and gluing the two chips together. ### Claim 14 (depends on 12) The method of claim 12, wherein hybridly integrating the chips comprises flipping the III-V gain-chip p-side down and bonding the gain-chip into a trench defined in the group IV semiconductor chip for edge coupling to the photonic integrated circuit. ### Claim 15 (depends on 12) The method of claim 12, wherein manufacturing the III-V semiconductor gain-chip comprises epitaxially growing a laser layer structure on a substrate by at least one of MBE or MOVPE growth. ### Claim 16 A laser-based sensor system-on-a-chip for real-time monitoring of a constituent concentration level in a subject, the system-on-a-chip comprising: a tunable hybrid III-V/IV sensor; and an optical interface coupled to the laser sensor, the optical interface comprising beam-shaping optics, wherein during use the laser sensor is remote from the subject, and the optical interface is configured to non-invasively illuminate a blood sample of the subject through the subject's skin or outer tissue. ### Claim 17 (depends on 16) A sensor comprising an array of cells, each cell comprising a laser-based sensor system-on-a chip of claim 16, wherein each array cell is targeted at a different spectral region and a separate target molecule. ### Claim 18 (depends on 16) The sensor array of claim 16, wherein the beam shaping optics comprise at least one optical element.