Implantable/Wearable System for on-line Monitoring

of Human Metabolic Conditions

(Implantable-IRONIC)

G. De Micheli,

Q. Huang, L. Thoeny-Meyer, Y. Leblebici,C. Dehollain, F. Grassi, S. Carrara

4

GlucoDay® and GlucoMenDay® consist of a micro-pump and a biosensor coupled to a micro-dialysis system

A. Menarini Diagnostics, Florence

Implanted devices for monitoring

In/Out tubing Almost only for diabetes Almost only for glucose

5

Fully implanted system with sensors, electronics and transmission

Target objective

Cylinder: about 2 mm in diameter and below 20 mm in length

6

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

7

The platform and its components

Specific components Probes and electrodes Chambers and fluidic circuits

Electronic components Transconductance amplifier and data conversion Transmission and powering

Powering

Transmission

Readout

Signal processing

Potentiostat

Probes

Electrodes

8

The electrochemical sensing principles

I

V

Oxidation peak

Reduction peak

Reduction Potential

Oxidation Potential

Peak position returns the molecule signature the sample

Peak current returns the concentration of the target

9

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

11

Cytochromes for biosensors

12

Electrode nanostructure

13

Enhanced Nano-Bio-Sensing

BARE ELECTRODE

CARBON NANOTUBES

CNTs + PROBE ENZYMES

14

Enhanced Nano-Bio-Sensing

VERTICAL

RANDOMLY ORIENTED

BENT

15

Sensor sensitivity is enhanced by nano-structuring the electrodes

~ 7.5 times more

Increased sensitivity

16

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

17

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

18

Block diagram of the Biosensing Platform

1.5

25 m

m

1.525 mm

First Block

Ramp generator

Third Block

Second Block

I/F converter

20

Energy & data transmission

Power consumption vs. complexity

Z(load)

21

Energy & data transmission

22

Prototype for in vivo remote monitoring

Léandre Bolomey, PhD. Thesis, EPFL

24

Glucose Monitoring (CNT+GOD)

25

Lactate Remote Monitoring (CNT+LOD)

26

ATP Monitoring (CNT+GOD+Hexokinase)

-700

-600

-500

-400

-300

-200

-100

0

0 200 400 600 800 1000 1200 1400

[ATP] uM

curr

ent

vari

atio

n (

nA

)

sensitivity: 34.2 pA/mM mm2

average standard deviation: 29.89

80

Sensitivity = 34.2 pA / mM mm2

Detection limit 346 μM

Interstitial ATP

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Performance of biosensors

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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

29

Thank you

1. Jacopo Olivo2. Sara Ghoreishizadeh3. Irene Taurino4. Enver Gürhan Kilinç 5. Giulia Siciliano 6. Roger Ulrich7. Tom Kleier8. Beat Muheim9. Michael Fairhead 10. Michael Richter

1. Thomas Burger2. Michele Proietti3. Renate Reiss4. Thomas Ramsauer5. Frank Gürkaynak

PhD Students

Scientists and Collaborators: