Implantable biosensor with automatic calibration

• US 8,548,552 B2
• Filed: 03/09/2010
• Issued: 10/01/2013
• Est. Priority Date: 03/09/2009
• Status: Expired due to Fees

• Current Assignee: Achilleas Tsoukalis
• Original Assignee: Achilleas Tsoukalis
• Inventors: Tsoukalis, Achilleas
• Primary Examiner(s): Kahelin, Michael
• Assistant Examiner(s): TRAN, THO Q
• Application Number:
  US12/720,334
• Publication Number:
  US 20100228110A1
• Time in Patent Office: 1,302 Days
• Field of Search: 600/365, 600/347, 600/345, 600/348, 600/349, 600/354, 600/396, 436/14, 604/504
• US Class Current: 600/347
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 5/14528 invasively
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence

Abstract

Implantable self-calibrating biosensor Subcutaneously or intracorporeally implantable biosensor, characterized by a closed microfluidic circuit with calibrating fluids, which communicates by a backward micro-dialysis logic with the exterior of said circuit, an open and in contact with the tissues and the interstitial fluid working electrode, for its self-calibration. One or more working electrodes may be positioned inside openable boxes from EAP, and be opened for the duration of the measurement and closed immediately after, succeeding one another in the measurement, as their sensitivity is diminished.

Claims

1. Self-calibrating disposable biosensor comprising an electronic part and an electrochemical part, wherein the electrochemical part comprises

a needle having an external surface configured to contact living tissue, said needle having in its interior a microfluidic circuit (8, 9) for the circulation of at least one calibration fluid, and

two or three electrodes (1, 2, 3) arranged on the external surface of the needle, one of the electrodes being a working electrode (1), said working electrode comprising porous bio-chemical sensing materials (30-32) configured to contact living tissue after implantation, and

means for fluid communication (4) of the microfluidic circuit (8,9) for the calibration fluid which is in the interior of said needle with the layers (29-32) of the working electrode on the external surface of the needle.

2. Biosensor as in claim 1, wherein a disposable nonimplantable extracorporeal part (40) comprises bags (5,6) with or without a protective cover, the bags containing calibration and draining fluids;

a drain vessel (7); and

pumps;

flow control valves; and

contacts with the electronic part for both the measurement and control of the calibration micro flow.

3. Biosensor as in claim 1 for measuring glucose, wherein the working electrode (1) comprises a conductive base made preferably of carbon or ferrocyanide/carbon or platinum or gold (29), nanofibers (30) with embedded immobilized glucose oxidase (31) and a coating of biomimetically synthesized silicon dioxide matrix (32).

4. Biosensor as in claim 1, further comprising pumping fingers and valves (10-14) for intermittently circulating one or more glucose solutions and fluids without glucose within the interior microfluidic circuit (8, 9) for self-calibration of the biosensor.

5. Biosensor as in claim 1, further comprising pumping fingers and valves (10-14) comprising electroactive polymers, said pumping fingers and valves (10-14) configured for pumping of the microflow and selection of a circulating fluid.

6. Biosensor as in claim 1, wherein the electronic part comprises a processing section comprising neural networks capable of processing a glucose measurement in the subcutaneous tissue taking into account insulin injection and of putting out a prediction of current venal blood glucose concentration and of venal blood glucose concentration after 30 minutes for triggering alerts.

7. Biosensor as in claim 6, wherein the processing section comprises means for current glucose prediction, those means allowing for algebraic addition of the concentration prediction by means of the kinetics of meal digestion and of the prediction of the consumption kinetics during and after exercise, to obtain a blood glucose concentration prediction for triggering alarms and calculating closed-loop injection.

8. Biosensor as in claim 7, wherein the processing section comprises means for transmitting differences between the predicted blood glucose value and the desired glucose value preferably to a PID (proportional/integral/Differential) algorithm to obtain a corresponding insulin injection correction and a robotic (closed loop) insulin injection correction.

9. Biosensor as in claim 1 further comprising a mechanical introducer for the implantation.

10. Implantable device comprising a plurality of biosensors comprising at least one biosensor according to claim 1, wherein each sensor comprises a lid, the lids being capable of exposing only the currently active sensor for a short interval, necessary for a measurement or a calibration and otherwise remaining closed, while the other sensors remaining hermetically closed till replacing the active sensor and wherein said lids can have a protective filter to avoid the introduction of larger than desired particles or molecules.

11. Implantable artificial pancreas comprising

a sensor according to claim 1,

means for closed-loop injection algorithms,

vessels for insulin, aqueous buffer, calibration and corrective injection glucose solution, those vessels being arranged at different heights, the vessels being elastic or collapsible bags, and

insulin-injection dual pumps effecting the transport of insulin injection and calibration fluids and the drainage of calibration wastes.

12. Biosensor as in claim 1, comprising bag pumping and measuring electronics, wherein the bag pumping and measuring electronics comprise microelectromechanical systems (MEMS) circuit, an electromechanical autonomous circuit, or a combination of both.