Cumulative measurement of an analyte
A method of monitoring the level of an analyte such as glucose in a subject comprises repeated steps of extracting a quantity of the analyte from the subject into a sample, for example using reverse iontophoresis, then measuring the concentration of the analyte with a method that depletes the analyte. Whereas known methods aim to deplete the analyte fully between extraction steps, the present method allows the concentration to build up with each cycle and measures successive changes in concentration. The higher concentrations present permit more reliable measurements to be made. The sample may be primed with an initial quantity of the analyte.
1. A method of operating a device for monitoring the level of an analyte in a subject, wherein the device includes a sensor, a sensor chamber, and a microelectronic circuit, comprising the steps of:
(a) operating the microelectronic circuit to monitor the sensor to develop a measurement of the concentration of the analyte in a sample;
(b) operating the microelectronic circuit to induce a flow of a bodily fluid from the subject into the sensor chamber, thereby introducing into the sample a quantity of the analyte that is representative of the level of analyte in the subject;
(c) operating the microelectronic circuit to monitor the sensor to develop another measurement of the concentration of the analyte in the sample;
(d) operating the microelectronic circuit to determine a level of the analyte in the subject based on the difference between the measurement of concentration developed in step (c) and an immediately preceding measurement of concentration; and
(e) repeating steps (b) to (d) at intervals to generate a sequence of determinations over time.
2. A method according to claim 1 , wherein:
the process used to measure the concentration of analyte in the sample partially depletes the analyte in the sample.
3. A method according to claim 2 , wherein the measurement in step (c) is controlled such that each measurement depletes only a small proportion of the analyte, whereby the concentration of analyte in the sample increases over successive intervals.
4. A method according to claim 2 , wherein:
the microelectronic circuit is operated to allow for depletion of analyte in the sample due to the measurement process when operated to determine the level of analyte in step (d).
5. A method according to claim 2 , wherein:
the microelectronic circuit is operated to allow for depletion of analyte in the sample during the intervals between successive measurements when operated to determine the level of analyte in step (d).
6. A method according to claim 2 , wherein there is a rest period between each measurement step (c) and the succeeding introduction step (b);
the method further comprising a step of operating the microelectronic circuit to monitor the sensor to develop an interim measurement of the concentration of the analyte in the sample immediately before each introduction step (b), that interim measurement to be used as the immediately preceding measurement of concentration in the determination step (d).
7. A method according to claim 1 , further comprising an initial step of introducing into the sample a quantity of the analyte prior to the first measurement step (a).
8. A method according to claim 7 , wherein the quantity of the analyte introduced into the sample in the initial step is from a source other than the subject.
9. A method according to claim 7 , wherein the initial step further comprises monitoring the sensor to carry out a set of repeated measurements of the concentration of the analyte in the sample in order to achieve stable operation of the sensor.
10. A method according to claim 1 , wherein the measurement step (c) comprises taking a series of measurements and calculating an average of selected measurements in the series.
11. A method according to claim 1 , wherein the determination step (d) comprises operating the microelectronic circuit to reject any measurements that give rise to a change in the determined level of analyte exceeding a threshold value.
12. A method according to claim 1 , wherein the determination step (d) comprises operating the microelectronic circuit to reject any measurements before the determined level of analyte has substantially stabilized.
13. A method according to claim 1 , wherein step (b) of introducing into the sample a quantity of the analyte that is representative of the level of analyte in the subject comprises performing reverse iontophoresis to extract the quantity of the analyte from interstitial fluid of the subject.
14. A method according to claim 1 , wherein step (b) of introducing into the sample a quantity of the analyte that is representative of the level of analyte in the subject comprises using microneedles to extract from the subject a bodily fluid containing the quantity of the analyte.
15. A method according to claim 1 , wherein the analyte is glucose.