# US 11,439,313 B2 · Small form factor digitally tunable NMR in vivo biometric monitor for metabolic state of a sample > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,313 B2 - Document ID: US11439313B2 - Status: Granted - Kind: B2 - Application number: 15/597,053 - Filed: 2017-05-16 - Published: 2017-11-16 - Granted: 2022-09-13 - Earliest claimed: 2016-05-16 - Assignees: Bitome, Inc. - Applicants: Bitome, Inc. - Inventors: Herbert B. Ryan; Jens Peter Höfflin; Trevor H. Kemp - Web page: https://patentgrep.com/patent/US11439313B2 ## CPC - A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging - A61B 5/4875: {Hydration status, fluid retention of the body} - A61B 5/6826: {Finger} - G01R 33/288: {Provisions within MR facilities for enhancing safety during MR, e.g. reduction of the specific absorption rate [SAR], detection of ferromagnetic objects in the scanner room} - G01R 33/34092: {RF coils specially adapted for NMR spectrometers} - G01R 33/3621: {NMR receivers or demodulators, e.g. preamplifiers, means for frequency modulation of the MR signal using a digital down converter, means for analog to digital conversion [ADC] or for filtering or processing of the MR signal such as bandpass filtering, resampling, decimation or interpolation} - G01R 33/3628: {Tuning/matching of the transmit/receive coil} - G01R 33/3804: {Additional hardware for cooling or heating of the magnet assembly, for housing a cooled or heated part of the magnet assembly or for temperature control of the magnet assembly} - G01R 33/422: of the radio frequency field - G01R 33/448: {Relaxometry, i.e. quantification of relaxation times or spin density (G01R33/50 takes precedence)} - G01R 33/465: applied to biological material, e.g. in vitro testing - A61B 5/6824: {Arm or wrist} - A61B 5/6825: {Hand} - A61B 5/6829: {Foot or ankle} - A61B 2503/10: Athletes - A61B 2560/0431: Portable apparatus, e.g. comprising a handle or case - G01R 33/302: {Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips} - G01R 33/34053: {Solenoid coils; Toroidal coils} - G01R 33/3678: {involving quadrature drive or detection, e.g. a circularly polarized RF magnetic field} - G01R 33/3808: {Magnet assemblies for single-sided MR wherein the magnet assembly is located on one side of a subject only; Magnet assemblies for inside-out MR, e.g. for MR in a borehole or in a blood vessel, or magnet assemblies for fringe-field MR} - G01R 33/383: using permanent magnets - G01R 33/3875: using correction coil assemblies, e.g. active shimming - G01R 33/389: Field stabilisation {, e.g. by field measurements and control means or indirectly by current stabilisation} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) ## Abstract Methods and apparatus for determining at least one metabolic state of a subject using a nuclear magnetic resonance (NMR) monitoring device. The NMR monitoring device comprises at least one magnet configured to generate a primary magnetic field, a transceiver coil arranged within the primary magnetic field, wherein the transceiver coil is configured to apply a time series of radiofrequency (RF) pulses to a portion of a subject located within the primary magnetic field and detect an NMR signal generated in response to application of the time series of RF pulses, and an NMR spectrometer communicatively coupled to the transceiver coil. The NMR spectrometer is configured to process the detected NMR signal to determine at least one metabolic state of the subject. ## Claims ### Claim 1 A nuclear magnetic resonance (NMR) monitoring device, comprising: at least one magnet configured to generate a primary magnetic field; a transceiver coil arranged within the primary magnetic field, wherein the transceiver coil is configured to apply a time series of radiofrequency (RF) pulses to a sample located within the primary magnetic field and to detect an NMR signal generated in response to application of the time series of RF pulses; a tuning circuit coupled to the transceiver coil, wherein the tuning circuit automatically adjusts a resonant frequency of the transceiver coil to a frequency associated with the primary magnetic field based on a dynamically determined transmitted signal, wherein the dynamically determined transmitted signal is different from the time series of RF pulses; and an NMR spectrometer having a software defined radio (SDR) architecture, wherein the NMR spectrometer is communicatively coupled to the transceiver coil, wherein the NMR spectrometer comprises: digital pulse generation circuitry configured to generate a digital representation of the time series of RF pulses; a digital-to-analog converter configured to convert the digital representation of the time series of RF pulses to an analog signal provided to the transceiver coil; an analog-to-digital converter configured to convert the detected NMR signal to a digital signal; and digital receive circuitry configured to process the digital signal to determine at least one metabolic state of the sample; at least one field sensor configured to measure at least one property of the primary magnetic field; at least one microcontroller unit configured to determine the frequency associated with the primary magnetic field based, at least in part, on the at least one measured property of the primary magnetic field and stored values; and wherein the tuning circuit comprises at least one digitally-tunable component arranged in series with the transceiver coil, and wherein the microcontroller unit is further configured to adjust a value of the at least one digitally-tunable component based, at least in part, on the determined frequency associated with the primary magnetic field. ### Claim 2 (depends on 1) The NMR monitoring device of claim 1, wherein the digital receive circuitry is configured to perform quadrature detection and bandpass filtering. ### Claim 3 (depends on 1) The NMR monitoring device of claim 1, wherein the analog-to-digital converter is configured to convert the detected NMR signal to the digital signal without first downconverting the detected NMR signal to baseband. ### Claim 4 (depends on 1) The NMR monitoring device of claim 1, further comprising: wherein the NMR spectrometer is further configured to adjust, during operation of the NMR monitoring device, a frequency of the RF pulses in the time series of RF pulses based on the frequency associated with the primary magnetic field. ### Claim 5 (depends on 1) The NMR monitoring device of claim 1, wherein the at least one magnet comprises a plurality of permanent magnets arranged in a Halbach configuration. ### Claim 6 (depends on 1) The NMR monitoring device of claim 1, further comprising a shielding structure arranged between the sample within the primary magnetic field and the transceiver coil, wherein the shielding structure is configured to electrically decouple the sample from the transceiver coil. ### Claim 7 (depends on 6) The NMR monitoring device of claim 6, wherein the shielding structure comprises a grating of conductive material. ### Claim 8 (depends on 1) The NMR monitoring device of claim 1, wherein the at least one field sensor comprises a temperature sensor and/or a magnetometer. ### Claim 9 (depends on 1) The NMR monitoring device of claim 1, further comprising: at least one shim coil configured to compensate for inhomogeneities in the primary magnetic field when a current flows through the at least one shim coil; and a feedback loop shim controller configured to automatically adjust a value of the current flowing through the at least one shim coil during operation of the NMR monitoring device. ### Claim 10 (depends on 9) The NMR monitoring device of claim 9, wherein the value of the current is automatically adjusted based, at least in part, on an intensity of the detected NMR signal. ### Claim 11 (depends on 9) The NMR monitoring device of claim 9, wherein the value of the current is automatically adjusted based, at least in part, on data received from at least one field sensor arranged within the primary magnetic field. ### Claim 12 (depends on 1) The NMR monitoring device of claim 1, further comprising a transmitter coil arranged near the transceiver coil to generate the dynamically determined transmitted signal, wherein the transceiver coil when operating in receive mode is configured to detect the dynamically determined transmitted signal from the transmitter coil in addition to the detected NMR signal, wherein the spectrometer is configured to quantify the detected NMR signal based, at least in part, on the detected dynamically determined transmitted signal from the transmitter coil. ### Claim 13 (depends on 1) The NMR monitoring device of claim 1, wherein determining the metabolic state of the sample comprises determining a hydration state of the sample. ### Claim 14 A method of monitoring a metabolic rate of a sample using a nuclear magnetic resonance (NMR) monitoring device, comprising: generating a primary magnetic field via at least one magnet; arranging a transceiver coil within the primary magnetic field, wherein the transceiver coil is configured to apply a time series of radiofrequency (RF) pulses to a sample located within the primary magnetic field and to detect an NMR signal generated in response to application of the time series of RF pulses; coupling a tuning circuit to the transceiver coil, wherein the tuning circuit automatically adjusts a resonant frequency of the transceiver coil to a frequency associated with the primary magnetic field based on a dynamically determined transmitted signal, wherein the dynamically determined transmitted signal is different from the time series of RF pulses; and communicatively coupling an NMR spectrometer having a software defined radio (SCR) architecture to the transceiver coil, where the NMR spectrometer comprises: generating a digital representation of the time series of RF pulses with digital pulse generation circuitry; converting the digital representation of the time series of RF pulses to an analog signal provided to the transceiver coil using a digital-to-analog converter; convert the detected NMR signal to a digital signal with an analog-to-digital converter; and processing the digital signal to determine at least one metabolic state of the sample using digital receive circuitry; measuring at least one property of the primary magnetic field with at least one field sensor; determining, with at least one microcontroller unit, the frequency associated with the primary magnetic field based, at least in part, on the at least one measured property of the primary magnetic field and stored values; and wherein the tuning circuit comprises at least one digitally-tunable component arranged in series with the transceiver coil, and wherein the microcontroller unit is further configured to adjust a value of the at least one digitally-tunable component based, at least in part, on the determined frequency associated with the primary magnetic field. ### Claim 15 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: configuring the digital receive circuitry to perform quadrature detection and bandpass filtering. ### Claim 16 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: converting, with the analog-to-digital converter, the detected NMR signal to the digital signal without first downconverting the detected NMR signal to baseband. ### Claim 17 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: adjusting with the NMR spectrometer, during operation of the NMR monitoring device, a frequency of the RF pulses in the time series of RF pulses based on the frequency associated with the primary magnetic field. ### Claim 18 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, wherein the at least one magnet comprises a plurality of permanent magnets arranged in a Hallbach configuration. ### Claim 19 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: electrically decoupling the sample from the transceiver coil by arranging a shielding structure between the sample within the primary magnetic field and the transceiver coil. ### Claim 20 (depends on 19) The method of monitoring a metabolic rate of a sample of claim 19, wherein the shielding structure comprises a grating of conductive material. ### Claim 21 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, wherein the at least one field sensor comprises a temperature sensor and/or a magnetometer. ### Claim 22 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: compensating, using at least one shim coil, for inhomogeneities in the primary magnetic field when a current flows through the at least one shim coil; and automatically adjusting, using a feedback loop shim controller, a value of the current flowing through the at least one shim coil during operation of the NMR monitoring device. ### Claim 23 (depends on 22) The method of monitoring a metabolic rate of a sample of claim 22, further comprising: automatically adjusting the value of the current based, at least in part, on an intensity of the detected NMR signal. ### Claim 24 (depends on 22) The method of monitoring a metabolic rate of a sample of claim 22, further comprising: automatically adjusting the value of the current based, at least in part, on data received from at least one field sensor arranged within the primary magnetic field. ### Claim 25 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: generating the dynamically determined transmitted signal based on a transmitter coil arranged near the transceiver coil, wherein the transceiver coil when operating in receive mode is configured to detect the dynamically determined transmitted signal from the transmitter coil in addition to the detected NMR signal; and quantifying, using the spectrometer, the detected NMR signal based, at least in part, on the detected dynamically determined transmitted signal from the transmitter coil. ### Claim 26 (depends on 14) The method of monitoring a metabolic rate of a sample of claim 14, further comprising: determining the metabolic state of the sample by determining a hydration state of the sample.