Presents: Towards an implantable continuous glucose sensor. by Erik Johannessen. Illustration: Flemming Sveen

Transcription

1 Presents: Towards an implantable continuous glucose sensor. by Erik Johannessen Illustration: Flemming Sveen

2 Π = i c RT, i = 1, n 2, 3... n Π = osmotic pressure (Pa) i = Van t Hoff factor c n = molar concentration (M) R = JK -1 mol -1 T = absolute temperature (K)

3 H 2 O Osmotic Pressure Principle of operation: LHS RHS

4 H 2 O Glucose Osmotic Pressure Principle of operation: LHS RHS

5 H 2 O Glucose Osmotic Pressure Principle of operation: LHS RHS

6 H 2 O Glucose Osmotic Pressure Principle of operation: LHS Membrane RHS

7 H 2 O Glucose Osmotic Pressure Principle of operation: LHS RHS

8 H 2 O Glucose Osmotic Pressure Principle of operation: ΔP ΔP LHS RHS

9 H 2 O Glucose Osmotic Pressure Principle of operation: Pressure sensor ΔP LHS RHS

10 Background SINTEF: Feasibility study - osmotic sensing of glucose, Prototype based on polymeric RO membranes Response time ~ 15 min : Microfabricated prototype BIA Research grant: 2.2 mill USD, Fig. 1: Prototype osmotic glucose sensor.

11 Why make it small? t = 2 x 2D cube (x) 1 mm volume 1 μl time (t) 500 s 100 μm 1 nl 5 s 10 μm 1 pl 50 ms -5 D = 10 cm -2s -1 x Smaller, reduced cost, power & reagent consumption Increased surface:volume ratio Control of heat flux (rapid heating&cooling - PCR) System integration: lab on a chip, lab in a pill

12 Biocompatibility Foreign Body Reaction Injury Blood-material interactions Provisional matrix formation Acute/Chronic inflammation Fibrosis/fibrous capsule development Phagocytosis Recognition by IgG (antibodies) Neutrophil/macrophage attachment Killing Frustrated Phagocytosis (non degradable implant material) Fig. 2: Provisional matrix with fresh blood vessels, 4 days Massive release of leukocyte products in attempt to destroy implant material Oxygen radicals, nitric oxide, anti microbial proteins, lysozyme

13 Membrane: Silicon, Si 3 N 4, SiO 2 Step 2: Support structure Step 1: Thin film membrane Membrane Step 3: Membrane element Step 5: Nanopore Step 4: Porosification of membrane Fig. 3: Osmotic membrane

14 Glucose Sensor Architecture: LTCC

15 Glucose Sensor Architecture: Sensor Membrane

16 Ref. Chamber Glucose Sensor Architecture:

17 Glucose Sensor Architecture: Access channel Bioassay

18 Glucose Sensor Architecture: Power ASIC

19 Glucose Sensor Architecture: Access hole Capsule Access hole

20 Glucose Sensor Architecture: 3 mm 7 mm

21 Glucose Sensor Power Transfer from Reader: Skin Sensor Tissue

22 2 10 mm Glucose Sensor Power Transfer from Reader:

23 Reader Glucose Sensor Power Transfer from Reader:

24 Glucose Sensor Signal back from sensor: Reader Sensor

25 LTCC Chip carrier New slides from KNT/VTT Fig. 4: Three generations of LTCC chip carriers: bonding pads (top), antenna (middle), and attached sensor components (bottom).

26 Assembled Sensor Module Fig. 5: Size relation of the Lifecare blood glucose sensor placed on the tip of the finger.

27 1 mm Ultra low Power ASIC Architecture 2nd prototype October 2008 (Dr. P. Häfliger, UiO) 90 nm gate technology Chip size: 1x1 mm 2 Circuits operating in weak inversion Operating voltage: 1 volts Power consumption: 200 µw power budget 20 μw continuous Inductive power and communication link Fig. 6: System architecture, ASIC. Resolution: 2.5 mg glucose/ dl

28 Implant Fig. 8: Reader Prototype reader and implant modules. Prototype reader & implant power module Reader: Coil: 6 turn x 19 mm diameter, 0.56 μh, Q-factor: 22 Power supply: 4.5V/ 27.5 ma ~ 110 mw Sine wave carrier MHz Transmission distance: 0-7 mm Implant: Spiral coil: 6 turn 3x7.3 mm, 4 layers, 1.2 μh, Q-factor: 11 Ind. power: 2.5 V/ 0.25 ma ~ 0.65 mw End to end power transfer efficiency ~ 0.6 % at 7 mm Tissue effect: < 15% reduction in transfer efficiency.

29 Performance Inductive Link c d Fig. 9: (a) Resonant frequency of MHz, and (b) falling field strength with distance. (c) Uplink modulation pulse from implant to reader; (d) downlink modulation pulse from reader to implant.

30 Milestones & Challenges Upcoming milestones Control the distribution of membrane pore sizes, current March 2009 Reduction in membrane pore size to target, current March 2009 Functional tests (physical properties), December 2007 May 2009 Biocompatibility & Medical tests, June 2008 August 2011 Chip carrier & Package, current May 2009 Microelectronic control system, current August 2009 Inductive power supply & Communication system, current May 2008

31 On The Path Towards An Artificial Pancreas A closed loop system with continuous blood glucose sensing and insulin delivery Source:

32 Acknowledgements