Method and system for tuning a closed-loop controller for an artificial pancreas

• US 9,486,578 B2
• Filed: 12/07/2012
• Issued: 11/08/2016
• Est. Priority Date: 12/07/2012
• Status: Active Grant

• Current Assignee: JDRF International
• Original Assignee: Animas Corporation (Johnson & Johnson)
• Inventors: Finan, Daniel, McCann, Thomas, Venugopalan, Ramakrishna
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US13/708,032
• Publication Number:
  US 20140163517A1
• Time in Patent Office: 1,432 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61M 2005/14296 Pharmacokinetic models
• CPC Class Codes: A61M 2205/3553 remote, e.g. between patient's home and doctor's office
• CPC Class Codes: A61M 2205/3561 local, e.g. within room or hospital
• CPC Class Codes: A61M 2205/3592 using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2205/702 automatically during use
• CPC Class Codes: A61M 2209/01 Remote controllers for specific apparatus
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

Described and illustrated is a system for management of diabetes that includes an infusion pump, glucose sensor and controller with a method programmed into the controller. The infusion pump is configured to deliver insulin to a subject. The glucose sensor is configured to sense glucose levels in the subject and provide output signals representative of the glucose levels in the subject. The controller is programmed receives signals from at least one of the glucose sensor and the pump and configured to issue signals to the pump to deliver an amount of insulin determined by a feedback controller that utilizes a model predictive control of the subject based on desired glucose levels, insulin amount delivered and measured glucose levels of the subject. The controller is also configured to deliver insulin using a tuning factor based on either one of an omission index module or a calibration index module.

Claims

1. A method to control an infusion pump with a controller to control the pump and receive data from at least one glucose sensor, the method comprising:

measuring glucose level in the subject with the glucose sensor to provide at least one glucose measurement in each time interval in a series of discrete time interval index (“

k”

);

obtaining in the controller a glucose calibration measurement of the glucose sensor during at least one time interval in the series of time interval index to provide for a calibration index;

ascertaining whether one or more glucose measurements were not provided by the glucose sensor during a time interval of the series of time interval index to provide for an omission index;

determining a tuning factor based on both the calibration index and omission index;

calculating insulin amount for delivery by the controller based on a model predictive controller that utilizes (a) the plurality of glucose measurements to predict a trend of the glucose level from estimates of a metabolic state of the subject and (b) the tuning factor so as to provide a calculated insulin amount to be delivered to the subject for each interval of the interval index;

delivering insulin amount determined from the calculating step with the infusion pump.

2. The method of claim 1, in which the tuning factor comprises an equation of the form

R(k)=R_NOM+r₁*CAL(k)+r₂*MISSED(k)

where:

R(k) comprises a tuning factor at each time interval index k such that R_MIN≦

R(k)≦

R_MAX;

R_NOM comprises a predetermined nominal tuning factor;

k comprises a discrete time interval index;

R_NOM≦

R_MAX≦

100*R_NOM;

R_NOM/100≦

R_MIN≦

R_NOM;

(R_MAX−

R_MIN)/500≦

r₁≦

(R_MAX−

R_MIN)/50;

(R_MAX−

R_MIN)/50≦

r₂≦

(R_MAX−

R_MJN)/5;

CAL(k) comprises a calibration index in which

CAL(k)=k−

k_cal−

6 (for k−

k_cal≧

6) or

CAL(k)=k−

k_cal2−

6 (for k−

k_cal<

6);

k_cal comprises the sample index of the most recent calibration for the continuous glucose sensor;

k_cal2 comprises the sample index of the second most recent calibration for the continuous glucose sensor;

MISSED(k) comprises an omission index in which one or more glucose values during the series of time intervals of the index k are missing or unreported to the controller.

3. The method of claim 2, in which the at least one glucose sensor comprises a continuous glucose sensor and an episodic glucose meter.

4. The method of claim 2, in which r₁ comprises any number from about 1 to about 50 and for r₂ comprises any number from about 10 to about 500.

5. A system for management of diabetes comprising:

an episodic glucose meter to measure blood glucose of a subject at discrete non-uniform time intervals and provide such episodic blood glucose level as a calibration index for each interval in a time interval index (k);

a continuous glucose monitor to continuously measure glucose level of the subject at discrete generally uniform time intervals and provide the glucose level at each interval in the form of glucose measurement data, in which any omission of a glucose measurement in any interval is stored in an omission index;

an insulin infusion pump to deliver insulin;

a controller in communication with the pump, glucose meter and the glucose monitor in which the controller determines a tuning factor based on (a) a calibration index derived from episodic blood glucose measurement and (b) an omission index for a model-predictive-control such that controller determines an insulin delivery rate for each time interval in the time interval index (k) from the model predictive control based on (1) desired glucose concentration, (2) glucose concentration measured by the monitor at each interval of the interval index (k), and (3) the tuning factor.

6. The system of claim 5, in which the tuning factor comprises an equation of the form

R(k)=R_NOM+r₁*CAL(k)+r₂*MISSED(k)

where:

R(k) comprises a tuning factor at each time interval index k such that R_MIN≦

R(k)≦

R_MAX;

R_NOM comprises a predetermined nominal tuning factor;

k comprises a discrete time interval index;

R_NOM≦

R_MAX≦

100*R_NOM;

R_NOM/100≦

R_MIN≦

R_NOM;

(R_MAX−

R_MIN)/500≦

r₁≦

(R_MAX−

R_MIN)/50;

(R_MAX−

R_MIN)/50≦

r₂≦

(R_MAX−

R_MIN)/5;

CAL(k) comprises a calibration index in which

CAL(k)=k−

k_cal−

6 (for k−

k_cal≧

6) or

CAL(k)=k−

k_ca12−

6 (for k−

k_cal<

6);

k_cal comprises the sample index of the most recent calibration for the continuous glucose sensor;

k_cal2 comprises the sample index of the second most recent calibration for the continuous glucose sensor;

MISSED(k) comprises an omission index in which one or more glucose values during the series of time intervals of the index k are missing or unreported to the controller.

7. The system of claim 6, in which r₁ comprises any number from about 1 to about 50 and for r₂ comprises any number from about 10 to about 500.