Method and system for closed-loop control of an artificial pancreas
First Claim
1. Apparatus for the delivery of insulin, the apparatus comprising:
- a) a glucose monitor adapted to measure respective glucose levels of a subject at discrete time intervals and provide respective glucose measurement data indicating each measured glucose level;
b) an insulin infusion pump configured to deliver insulin in response to a delivery control signal;
c) a memory configured to store a plurality of basal insulin delivery amounts at respective ones of the discrete time intervals; and
d) a model predictive controller adapted to, for each of a plurality of the discrete time intervals;
i) receive the glucose measurement data for that time interval from the glucose monitor;
ii) determine an insulin delivery amount for that time interval using model predictive control based on a selected target glucose concentration range, the received glucose measurement data, the stored basal insulin delivery profile amounts for that time interval and n−
1 successive time intervals; and
iii) provide to the insulin infusion pump a delivery control signal corresponding to the determined insulin delivery amount, so that a corresponding amount of insulin is delivered by the infusion pump;
e) in which the model predictive controller is adapted to determine the insulin delivery amount by mathematical minimization of a cost function that computes a cost metric correlated with physiological-fluid glucose-level excursions from a selected target glucose range for a particular set of n successive candidate insulin delivery amounts beginning from the selected one of the time intervals, and the model predictive controller, in order to carry out the mathematical minimization, is adapted to;
i) select n candidate insulin delivery values for a real-type n-dimensional test point;
ii) for each dimension i of the n dimensions;
A) set a complex-type n-dimensional computation point c equal to the test point;
B) set an imaginary part of element i of c equal to a nonzero increment;
C) compute a complex-type value of the cost function at c; and
D) divide the imaginary part of the complex-type computed function value by the increment to form element i of an approximate Jacobian of the function at the test point;
iii) for each pair of dimensions (i,j), each i and j one of the n dimensions;
A) set a multicomplex-type n-dimensional computation point b equal to the test point;
B) set a first imaginary part of element i of b equal to a nonzero first increment;
C) set a second imaginary part of element j of b equal to a nonzero second increment;
D) compute a multicomplex-type value of the cost function at b; and
E) divide the third imaginary part of the computed multicomplex-type function value by the product of the first and second increments to form element (i,j) of an approximate Hessian of the function at the test point;
iv) solve a system of equations defined by the approximate Hessian and the approximate Jacobian to find a delta;
v) modify the test point according to the delta to form a next point;
vi) determine whether the next point satisfies selected convergence criteria;
vii) if not, assign the value of the next point to the test point and repeat the computation of the approximate Jacobian and Hessian of the function, solution of the system of equations, modification of the test point, and determination of whether the next point satisfies the selected convergence criteria; and
viii) if so, select the first element of the next point as the candidate insulin delivery amount for the selected one of the time intervals;
f) and further in which the model predictive controller is adapted to, in order to compute the cost function for each input set of n successive candidate insulin delivery amounts;
i) predict an excursion of the glucose level from a selected target glucose range using at least some of the glucose measurements, a glucose-insulin dynamic model of the subject, and an input set of n candidate insulin delivery amounts;
ii) compute a deviation of the candidate insulin delivery amounts from respective selected basal delivery amounts; and
iii) form a weighted sum of respective values representing the predicted excursion and the computed deviation using respective selected weights, such that the output of the cost function includes the weighted sum; and
g) deliver, with the insulin infusion pump, the determined insulin delivery amount of insulin to the subject, as provided by the delivery control signal from the controller.
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Abstract
A local extremum of a function ƒ is determined by computing a Jacobian of ƒ at a test point x by adding an imaginary part to x and a Hessian of ƒ by adding two imaginary parts to a multicomplex copy of x and extracting a third imaginary part. Solving a system of equations defined by the Jacobian and Hessian yields a delta; the process is repeated until convergence. This method is used in each of a series of time intervals to compute an insulin-delivery amount for an insulin pump. ƒ is a model-predictive-control cost function; x is a set of successive candidate insulin delivery amounts beginning from a selected time interval. A system includes a glucose monitor and a controller using glucose measurement data therefrom to determine an insulin delivery amount for a time interval by minimizing ƒ; an insulin pump provides insulin corresponding to the delivery amount.
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Citations
13 Claims
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1. Apparatus for the delivery of insulin, the apparatus comprising:
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a) a glucose monitor adapted to measure respective glucose levels of a subject at discrete time intervals and provide respective glucose measurement data indicating each measured glucose level; b) an insulin infusion pump configured to deliver insulin in response to a delivery control signal; c) a memory configured to store a plurality of basal insulin delivery amounts at respective ones of the discrete time intervals; and d) a model predictive controller adapted to, for each of a plurality of the discrete time intervals; i) receive the glucose measurement data for that time interval from the glucose monitor; ii) determine an insulin delivery amount for that time interval using model predictive control based on a selected target glucose concentration range, the received glucose measurement data, the stored basal insulin delivery profile amounts for that time interval and n−
1 successive time intervals; andiii) provide to the insulin infusion pump a delivery control signal corresponding to the determined insulin delivery amount, so that a corresponding amount of insulin is delivered by the infusion pump; e) in which the model predictive controller is adapted to determine the insulin delivery amount by mathematical minimization of a cost function that computes a cost metric correlated with physiological-fluid glucose-level excursions from a selected target glucose range for a particular set of n successive candidate insulin delivery amounts beginning from the selected one of the time intervals, and the model predictive controller, in order to carry out the mathematical minimization, is adapted to; i) select n candidate insulin delivery values for a real-type n-dimensional test point; ii) for each dimension i of the n dimensions; A) set a complex-type n-dimensional computation point c equal to the test point; B) set an imaginary part of element i of c equal to a nonzero increment; C) compute a complex-type value of the cost function at c; and D) divide the imaginary part of the complex-type computed function value by the increment to form element i of an approximate Jacobian of the function at the test point; iii) for each pair of dimensions (i,j), each i and j one of the n dimensions; A) set a multicomplex-type n-dimensional computation point b equal to the test point; B) set a first imaginary part of element i of b equal to a nonzero first increment; C) set a second imaginary part of element j of b equal to a nonzero second increment; D) compute a multicomplex-type value of the cost function at b; and E) divide the third imaginary part of the computed multicomplex-type function value by the product of the first and second increments to form element (i,j) of an approximate Hessian of the function at the test point; iv) solve a system of equations defined by the approximate Hessian and the approximate Jacobian to find a delta; v) modify the test point according to the delta to form a next point; vi) determine whether the next point satisfies selected convergence criteria; vii) if not, assign the value of the next point to the test point and repeat the computation of the approximate Jacobian and Hessian of the function, solution of the system of equations, modification of the test point, and determination of whether the next point satisfies the selected convergence criteria; and viii) if so, select the first element of the next point as the candidate insulin delivery amount for the selected one of the time intervals; f) and further in which the model predictive controller is adapted to, in order to compute the cost function for each input set of n successive candidate insulin delivery amounts; i) predict an excursion of the glucose level from a selected target glucose range using at least some of the glucose measurements, a glucose-insulin dynamic model of the subject, and an input set of n candidate insulin delivery amounts; ii) compute a deviation of the candidate insulin delivery amounts from respective selected basal delivery amounts; and iii) form a weighted sum of respective values representing the predicted excursion and the computed deviation using respective selected weights, such that the output of the cost function includes the weighted sum; and g) deliver, with the insulin infusion pump, the determined insulin delivery amount of insulin to the subject, as provided by the delivery control signal from the controller. - View Dependent Claims (2, 3, 4, 5)
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6. A method to control an infusion pump responsive to a controller that receives data from a glucose sensor, the method comprising:
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a) measuring respective glucose levels of a physiological fluid from a subject for each time interval of a series of discrete time intervals using the glucose sensor; and b) using a controller, automatically calculating an insulin delivery amount for a selected one of the time intervals by mathematically minimizing a cost function that computes a cost metric correlated with physiological-fluid glucose-level excursions from a selected target glucose range for a particular set of n successive candidate insulin delivery amounts beginning from the selected one of the time intervals, the minimizing including; i) selecting n candidate insulin delivery values for a real-type n-dimensional test point; ii) computing an approximate Jacobian of the cost function at the test point by evaluating the cost function, in which the model predictive controller computes the cost function for each input set of n successive candidate insulin delivery amounts by; A) predicting an excursion of the glucose level from a selected target glucose range using at least some of the glucose measurements, a glucose-insulin dynamic model of the subject, and the candidate insulin delivery amounts; B) computing a deviation of the candidate insulin delivery amounts from respective selected basal delivery amounts; and C) forming a weighted sum of respective values representing the predicted excursion and the computed deviation using respective selected weights such that the output of the cost function includes the weighted sum; iii) computing an approximate Hessian of the cost function at the test point by evaluating the cost function; iv) solving a system of equations defined by the approximate Hessian and the approximate Jacobian to find a delta; v) modifying the test point according to the delta to form a next point; vi) determining whether the next point satisfies selected convergence criteria; vii) if not, assigning the value of the next point to the test point and repeating the computing of the approximate Jacobian and Hessian, solving the system of equation, modifying the test point and the determining step; and viii) if so, selecting a first element of the next point as the candidate insulin delivery amount for the selected one of the time intervals; (c) commanding, with a control signal from the controller, the infusion pump to deliver the calculated insulin delivery amount to the subject; and d) delivering, with the infusion pump, the calculated insulin delivery amount of insulin to the subject. - View Dependent Claims (7, 8, 9, 10, 11, 12, 13)
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Specification