Substance monitoring and control in human or animal bodies

Patent metadata

Field	Value
Publication number	US-8977504-B2
Application number	US-68254308-A
Country	US
Kind code	B2
Filing date	Oct 10, 2008
Priority date	Oct 12, 2007
Publication date	Mar 10, 2015
Grant date	Mar 10, 2015

Abstract

Apparatus for monitoring a substance in human or animal in real time, the apparatus comprising a sensor providing a time series of measurements of substance level, said measurements being indicative of an inferred level of said substance in a part of said human or animal and a processor which applies an interacting multiple model strategy to a system model to provide a combined estimate of the inferred substance level from the substance level measurements. The substance may be glucose. The apparatus may also be adapted to control said substance using said interacting multiple model strategy to a system model to provide a combined estimate of a dose to be applied.

First claim

The invention claimed is:

1. Apparatus for real time control of glucose in a human or an animal, the apparatus comprising:
a sensor providing a time series of measurements of glucose level, said measurements being indicative of an inferred level of said glucose in a part of said human or animal,
a processor which is adapted to perform the following steps:
calculate a first estimate of said inferred glucose level from said measured glucose level using a first glucoregulatory system model,
calculate a second estimate of said inferred glucose level from said measured glucose level using a second glucoregulatory system model with said second system model being a variation of said first system model, and
predict a combined estimate of the inferred glucose level based on a combination of the first and second estimates,

wherein the processor is a state estimator and is adapted to define a state vector for each model, the state vector comprising a set of variables each having an associated uncertainty, the set of variables including a variable representing an unexplained change in glucose level with each model having a different standard deviation in the unexplained change in glucose level;
wherein the first and second glucoregulatory models each comprise a sub-model of glucose kinetics in the blood of said human or animal, a sub-model of interstitial glucose kinetics, a sub-model of insulin absorption, a sub-model of insulin action and a sub-model of gut absorption; and
wherein the state vector includes the following states
x k =( q 1ƒ,k ,q 2ƒ,k u S,k ,F k ,q 3ƒ,k ) T

where q 1ƒ,k , q 2ƒ,k , and q 3ƒ,k represent glucose amounts in the accessible, non-accessible, and interstitial compartments excluding the contribution from meals, u s,k is the unexplained glucose influx and F k is glucose availability, and a dispenser that delivers a specified amount of medication to a user in response to a command from the processor based on the predicted combined estimate of the inferred glucose level.

2. Apparatus according to claim 1 , wherein the processor is adapted to calculate a combined estimate by weighting each estimate according to an associated mixing probability representing a respective probability of each said model correctly predicting said glucose level.

3. Apparatus according to claim 2 , wherein the processor is further adapted to update said mixing probability responsive to a difference between said predicted glucose level measurement of each respective said model and said glucose level measurement from said sensor.

4. Apparatus according to claim 1 , further comprising a user monitor to receive inputs from the user and/or to display the status of the apparatus.

5. Apparatus according to claim 1 , wherein the sensor measures the glucose intravenously, subcutaneously and/or intradermally.

6. Apparatus according to claim 1 , further comprising a real-time alarm which is activated when the combined estimate or the combined estimate of future glucose level is below a preset hypoglycaemia threshold or above a preset hyperglycaemia threshold.

7. Apparatus for real time control of a substance in a human or an animal, the apparatus comprising:
a sensor providing a time series of measurements of substance level, said measurements being indicative of an interred level of said substance in a part of said human or animal,
a processor which applies an interacting multiple model strategy to a system model to predict a combined estimate of the inferred substance level from the substance level measurements,
wherein the interacting multiple model strategy comprises first and second glucoregulatory models each of which comprise a sub-model of glucose kinetics in the blood of said human or animal, a sub-model of interstitial glucose kinetics, a sub-model of insulin absorption, a sub-model of insulin action and a sub-model of gut absorption;
wherein said inferred substance level comprises a level of glucose in said blood and said substance level measurements comprise measurements of an interstitial glucose level;
wherein the processor is a state estimator and is adapted to define a state vector for each model, the state vector comprising a set of variables each having an associated uncertainty, the set of variables including a variable representing an unexplained change in glucose level with each model having a different standard deviation in the unexplained change in glucose level;
wherein the state vector includes the following states
x k e =( i 1,k ,i 2,k ,r D,k ,r E,k ,a 1,k ,a 2,k ,q 1,k ,q 3,k ,u S,k ) T

where i 1,k and i 2,k is the amount of insulin in the two subcutaneous insulin depots at time k, r D,k and r E,k are the remote insulin actions affecting glucose disposal and endogenous glucose production, a 1,k and a 2,k are the amount of glucose in the two absorption compartments q 1,k , q 2,k , q 3,k represent glucose amounts in the accessible, non-accessible, and interstitial compartments and u s,k is the unexplained glucose influx; and
wherein said processor is configured to apply the interacting multiple model strategy to calculate a first estimate for said inferred glucose level from said measured substance level using said first glucoregulatory system model, calculate a second estimate for said inferred glucose level from said measured substance level using said second glucoregulatory system model and predict said combined estimate of the inferred glucose level based on a combination of said first and second estimates, and a dispenser that delivers a specified amount of medication to a user in response to a command from the processor based on the predicted combined estimate of the inferred glucose level.

8. Apparatus for real time control of glucose in a human or an animal, the apparatus comprising:
a sensor providing a time series of measurements of glucose level, said measurements being indicative of an inferred level of said glucose in a part of said human or animal;
a processor which is adapted to
construct at least two state vectors each comprising a set of variables for a respective one of at least two glucose level models, said state vectors representing states of said at least two models, said state vectors also including a variable representing an uncertainty in a change in glucose level with time, each of said variables having an associated probability distribution;
predict a value of a said glucose level using said probability distribution and said state vectors;
update values of said state vectors responsive to a difference between a predicted glucose level measurement for each said model and a glucose level measurement from said sensor;
update a mixing probability representing a respective probability of each said model correctly predicting said glucose level responsive to a difference between said predicted glucose level measurement of each respective said model and said glucose level measurement from said sensor; and
determine a combined predicted glucose level measurement for said human or animal by combining outputs from said glucose level models according to said updated mixing probability,

wherein said at least two models each comprise a sub-model of glucose kinetics in the blood of said human or animal, a sub-model of interstitial glucose kinetics, a sub-model of insulin absorption, a sub-model of insulin action and a sub-model of gut absorption; and
wherein the state vector includes the following states
x k =( q 1ƒ,k ,q 2ƒ,k ,u S,k ,F k ,q 3ƒ,k ) T

where q 1ƒ,k , q 2ƒ,k , and q 3ƒ,k represent glucose amounts in the accessible, non-accessible, and interstitial compartments excluding the contribution fro

Assignees

• Hovorka Roman
• Cambridge Entpr Ltd

Inventors

• Hovorka Roman

Classifications

• G16Z99/00

  Subject matter not provided for in other main groups of this subclass · CPC title

• G16H50/50

  for simulation or modelling of medical disorders · CPC title

• G16H50/20

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• G16H20/17 Primary

  delivered via infusion or injection · CPC title

• A61M5/1723 Primary

  using feedback of body parameters, e.g. blood-sugar, pressure (measurement of body parameters A61B5/00) · CPC title