1. G. De Micheli,
Q. Huang, L. Thoeny-Meyer, Y. Leblebici,
C. Dehollain, F. Grassi, S. Carrara
Implantable/Wearable System for
on-line Monitoring
of Human Metabolic Conditions
(Implantable-IRONIC)

2. Implanted devices for monitoring
 In/Out tubing
 Almost only for diabetes A. Menarini Diagnostics, Florence
 Almost only for glucose
GlucoDay® and GlucoMenDay® consist of a micro-pump
and a biosensor coupled to a micro-dialysis system
4

3. Target objective
Cylinder: about 2 mm in diameter
and below 20 mm in length
Fully implanted system with
sensors, electronics and transmission 5

4. Challenges in implant design
 Miniaturization:
 Small size, low-power consumption, low-impact
 Biocompatibility:
 Membrane design
 A set of target measurements
 Molecules, pH, temperature, pressure
 Reliable, highly-sensitive readout electronics
 Data processing and/or transmission
 Commercial feasibility is related to volume production
Platform-based design
6

5. The platform and its components
 Specific components
 Probes and electrodes
 Chambers and fluidic circuits
 Electronic components
 Transconductance amplifier and data conversion
 Transmission and powering
Probes
Electrodes
Readout Potentiostat
Signal processing
Transmission
Powering
7

6. The electrochemical sensing principles
Oxidation peak
Oxidation Potential
V
Reduction Potential
I
Reduction peak
Peak position returns the molecule signature the sample
Peak current returns the concentration of the target
8

7. Electrode functionalization
 A probe is a molecule reacting with a selected target
 Many possibilities
 Our goal is modularity and targeting proteins
 Oxidases (e.g., glucose oxidase)
 React with target and release H2O2
 H2O2 oxidizes at a specific potential (close to 650mv) generating
current
 Chronoamperometry – measure current in a time window
 Cytochrome P450 (family of enzymes)
 React with target(s) and generate current at specific potentials
 Cyclic voltammetry– measure current while sweeping voltage
9

8. Cytochromes for biosensors
11

9. Electrode nanostructure
12

10. Enhanced Nano-Bio-Sensing
BARE ELECTRODE
CARBON NANOTUBES
CNTs + PROBE ENZYMES
13

11. Enhanced Nano-Bio-Sensing
RANDOMLY ORIENTED
VERTICAL
BENT
14

12. Increased sensitivity
~ 7.5 times more
Sensor sensitivity is enhanced by
nano-structuring the electrodes 15

13. Single/multiple target sensing
 Extending or arraying the probes
 Proximity and interference of molecules
 Separate chambers and fluidics
 Using probe with different redox potentials
 Cyclic voltammetry
 Analyze different redox peaks
Etoposide electrochemical detection
16

14. Platform design challenges
 Design modular platform that can be adapted to
 Single/multiple targets
 Parametrize components and potentiostat
 Potentials must vary slowly
 Watch out for drifts and noise
 Transconductance amplifier
 High-sensitivity, linearity, low noise
 Overall low-power consumption for data acquisition,
processing and transmission
 Power can be transmitted as magnetic field
17

15. Block diagram of the Biosensing Platform
18

16. First Block Third Block
1.525 mm
Second I/F
Block converter
Ramp generator
1.525 mm

17. Energy & data transmission
Z(load)
Power consumption vs. complexity
20

18. Energy & data transmission
21

19. Prototype for in vivo remote monitoring
LéandreBolomey, PhD. Thesis, EPFL
22

20. Glucose Monitoring (CNT+GOD)
24

21. Lactate Remote Monitoring (CNT+LOD)
25

22. ATP Monitoring (CNT+GOD+Hexokinase)
-700
Sensitivity = 34.2 pA / M mm2
-600
Detection limit 346 μM
current variation (nA)
-500
average standard deviation: 29.89
-400 sensitivity: 34.2 pA/ M mm2
Interstitial ATP
-300
-200
-100
0
80
0 200 400 600 800 1000 1200 1400
[ATP] uM 26

23. Performance of biosensors
27

24. Conclusions
 Medical implants are an important testbed for
advanced electronic and sensor design
 Specific issues relate to co-design of sensors and
electronics:
 New materials, nanostructuring, new circuits
 Low-energy sensing and computation
 Platform-based design is key to low-cost production
and to commercialization
 Challenges to integration are both technical and commercial
28

25. Thank you
PhD Students
1. Jacopo Olivo
2. Sara Ghoreishizadeh
3. Irene Taurino
4. EnverGürhan Kilinç
5. Giulia Siciliano
6. Roger Ulrich Scientists and Collaborators:
7. Tom Kleier 1. Thomas Burger
8. Beat Muheim 2. Michele Proietti
9. Michael Fairhead 3. Renate Reiss
10. Michael Richter 4. Thomas Ramsauer
5. Frank Gürkaynak
29