Methods of in-vitro analysis using time-domain NMR spectroscopy
View Patent ↗An in vitro method of determining an analyte concentration of a sample includes placing the sample into a low-field, bench-top time-domain nuclear magnetic resonance (TD-NMR) spectrometer. The NMR spectrometer is tuned to measure a selected type of atom. A magnetic field is applied to the sample using a fixed, permanent magnet. At least one 90 degree radio-frequency pulse is applied to the sample. The radio-frequency pulse is generally perpendicular to the magnetic field. The 90 degree radio-frequency pulse is removed from the sample so as to produce a decaying NMR signal. The decaying NMR signal is measured at a plurality of times while applying a plurality of 180 degree refocusing radio-frequency pulses to the sample. The analyte concentration is calculated from the plurality of measurements associated with the decaying NMR signal and a selected model.
1. An in vitro method of determining an analyte concentration of a sample, the method comprising the acts of:
placing a sample into a low-field, bench-top time-domain nuclear magnetic resonance (TD-NMR) spectrometer, the NMR spectrometer being tuned to measure a selected type of atom;
applying a magnetic field to the sample;
applying at least one radio-frequency pulse to the sample;
removing the radio-frequency pulse from the sample so as to produce a T 2 relaxation signal;
measuring the T 2 relaxation signal; and
calculating an analyte concentration from the measurement associated with the T 2 relaxation signal.
2. The method of claim 1 , wherein the sample is a body fluid.
3. The method of claim 2 , wherein the sample is a blood plasma sample.
4. The method of claim 2 , wherein the sample is a blood serum sample.
5. The method of claim 2 , wherein the sample is a urine sample.
6. The method of claim 1 , wherein the method is a reagentless method.
7. The method of claim 1 , further comprising associating the T 2 relaxation signal with a model.
8. The method of claim 7 , wherein the model is a multivariate calibration model.
9. The method of claim 1 , wherein the NMR spectrometer includes a permanent magnet less than about 1.4 tesla in the absence of hardware or electronics for locking or shimming.
10. The method of claim 1 , wherein the selected type of atom is hydrogen.
11. The method of claim 1 , wherein the T 2 relaxation signal is a decaying signal.
12. A method of determining an analyte concentration of a sample, the method comprising the acts of:
placing a sample into a low-field, bench-top time-domain nuclear magnetic resonance (TD-NMR) spectrometer, the NMR spectrometer being tuned to measure hydrogen;
applying a magnetic field to the sample;
applying at least one radio-frequency pulse to the sample;
removing the radio-frequency pulse from the sample so as to produce a T 2 relaxation signal;
measuring the T 2 relaxation signal; and
calculating an analyte concentration from the measurement associated with the T 2 relaxation signal.
13. The method of claim 12 , wherein the analyte is one of glucose, cholesterol, triglycerides, globulin, albumin, protein, blood urea nitrogen, alkalinie phosphastase, or creatinine.
14. The method of claim 12 , wherein the sample comprises blood plasma.
15. The method of claim 12 , wherein the sample comprises blood serum.
16. The method of claim 12 , wherein the sample comprises urine.
17. The method of claim 12 , wherein the sample is reagentless.
18. The method of claim 12 , wherein the NMR spectrometer comprises at least one fixed, permanent magnet.
19. The method of claim 12 , wherein the NMR spectrometer includes a permanent magnet less than about 1.4 tesla in the absence of hardware or electronics for locking or shimming.
20. The method of claim 12 , further comprising associating the T 2 relaxation signal with a model.