A benchtop closed-loop system controlled by a bio-inspired silicon implementation of the pancreatic beta cell.
The normal pancreatic beta-cell membrane depolarizes in response to increasing concentrations of glucose in a bursting pattern. At <7 mM (126 mg/dl), the cell is electrically silent. The bursting pulse width increases as glucose rises >7 mM (126 mg/dl) until a continuous train of bursting is seen at >25 mM (450 mg/dl). A bio-inspired silicon device has been developed using analogue electronics to implement membrane depolarization of the beta cell. The device is ultralow powered, miniaturized (5 x 5 mm), and produces a bursting output identical to that characterized in electrophysiological studies.


OBJECTIVE
The goal of this study was to demonstrate the ability of silicon implementation of beta-cell electrophysiology to respond to a simulated glucose input and to drive an infusion pump in vitro.


METHODS
The silicon device response to a current source was recorded at varying simulated glucose concentrations. Subsequently, the bursting response to a changing analyte concentration measured by an amperometric enzyme electrode was converted to a voltage, driving a syringe pump loaded with a 50-ml syringe containing water.


RESULTS
Bursting responses are comparable to those recorded in electrophysiology. Silicon beta-cell implementation bursts with a pulse width proportional to concentration and is able to drive an infusion pump.


CONCLUSIONS
This is the first in vitro demonstration of closed loop insulin delivery utilizing miniaturized silicon implementation of beta-cell physiology in analogue electronics.
Institute of Biomedical Engineering, Imperial College, London, UK. nick.oliver@imperial.ac.uk
Nick
N
Oliver
Pantelis
P
Georgiou
Desmond
D
Johnston
Christofer
C
Toumazou
D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D019719:Diagnostic Equipment; D004867:Equipment Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008422:Materials Testing; D008564:Membrane Potentials; D008904:Miniaturization; D008954:Models, Biological; D008991:Monitoring, Physiologic / Q000295:instrumentation*; D012825:Silicon; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D012825:Silicon