Sensor for measuring the activity of beta-pancreatic cells or of islets of langerhans, manufacture and use of such a sensor

• US 9,962,113 B2
• Filed: 01/12/2011
• Issued: 05/08/2018
• Est. Priority Date: 01/13/2010
• Status: Active Grant

• Current Assignee: Centre National De La Recherche Scientifique, Institut polytechnique de Bordeaux, Universite Bordeaux Segalen, Universite De Bordeaux I
• Original Assignee: Centre National De La Recherche Scientifique, Institut polytechnique de Bordeaux, Universite Bordeaux Segalen, Universite De Bordeaux I
• Inventors: Lang, Jochen, Catargi, Bogdan, Renaud, Sylvie, Raoux, Matthieu, Charpentier, Gilles
• Primary Examiner(s): Cohen, Lee S
• Assistant Examiner(s): Cardinal, Erin M
• Application Number:
  US13/521,724
• Publication Number:
  US 20130030271A1
• Time in Patent Office: 2,673 Days
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/425 pancreas
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• 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 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

The invention relates to a sensor (2) including: a microelectrode assembly (21); and β-pancreatic cells (23) or islets (230) of Langerhans in culture on the microelectrode assembly (21); characterized in that the microelectrode assembly (21) is designed to measure dynamically, continuously and in real time, electrical signals (V) produced by the β-pancreatic cells (23) or the islets of Langerhans (230) upon physiological activation. The invention also relates to the field of devices that can be implantable in the body of a patient, and including an insulin dispenser for dispensing an amount of insulin. The invention also relates to a method for manufacturing such a sensor and to such a device and a use of such a sensor.

Claims

1. A sensor including:

microelectrodes which are configured to dynamically measure in real time and continuously, electrical signals produced by all cells types in islets of Langerhans in culture disposed on the microelectrodes during their physiological activation, wherein the sensor also includes at least one set of processing units, in which each processing unit is coupled to a corresponding one of said microelectrodes and;

each processing unit is configured to process the electrical signals measured by said corresponding one of said microelectrodes and extract at least one parameter from said processed electrical signals indicating a need for insulin by a patient, in real time and continuously.

2. The sensor of claim 1, in which at least one of the processing units is configured to detect action potentials in the electrical signals.

3. The sensor of claim 1, also including a regulator for transforming the parameter indicating the need for insulin into a control signal for controlling an insulin dispenser.

4. The sensor of claim 1, also including a semiconductor substrate comprising at least the microelectrodes.

5. The sensor of claim 1, also including a semi-permeable membrane, for:

filtering a liquid needing access to the islets of Langerhans, and

blocking the molecules of said liquid of which the weight is greater than 65 kDa.

6. The sensor of claim 5, configured to be implanted in the patient'"'"'s body.

7. The sensor of claim 1, in which the islets of Langerhans are of porcine, murine or human origin.

8. The sensor of claim 1, in which each processing unit:

extracts at least one parameter indicating the state of electrical activity of the islets of Langerhans for;

a physiological study for screening toxic molecules;

or

a physiological study for a therapeutic end;

or

a physiological study for monitoring the differentiation of cells from stem cells into β

-pancreatic cells.

9. The sensor of claim 1, wherein each said processing unit includes an action potentials detector sub-unit and an extraction sub-unit.

10. The sensor of claim 1, wherein the processing units are analog microelectronic units.

11. The sensor of claim 10 wherein the analog microelectronic units include sub-micronic CMOS technology.

12. The sensor of claim 1, wherein the at least one parameter is calculated from the processed electrical signals and a set-point value.

13. A device including an insulin dispenser for dispensing an amount of insulin into the patient'"'"'s body, and the sensor of claim 1, wherein the sensor is configured to control the insulin dispenser.

14. The device of claim 13, which is configured to be implantable into the patient'"'"'s body.

15. A process for producing the sensor of claim 1, including:

providing a substrate having the microelectrodes and the processing units,

cleaning the substrate with plasma;

culturing islets of Langerhans on the microelectrodes.

16. The sensor according to claim 1, wherein each said processing unit is configured for processing the electrical signals according to mathematical functions of at least one of amplification and filtration.