G. De Micheli,Q. Huang, L. Thoeny-Meyer, Y. Leblebici,   C. Dehollain, F. Grassi, S. CarraraImplantable/Wearable System fo...
Implanted devices for monitoring In/Out tubing Almost only for diabetes       A. Menarini Diagnostics, Florence Almost ...
Target objectiveCylinder: about 2 mm in diameter   and below 20 mm in length            Fully implanted system with       ...
Challenges in implant design Miniaturization:    Small size, low-power consumption, low-impact Biocompatibility:    Me...
The platform and its components Specific components    Probes and electrodes    Chambers and fluidic circuits Electron...
The electrochemical sensing principles                                                              Oxidation peak        ...
Electrode functionalization A probe is a molecule reacting with a selected target    Many possibilities    Our goal is ...
Cytochromes for biosensors                             11
Electrode nanostructure                          12
Enhanced Nano-Bio-Sensing           BARE ELECTRODE              CARBON NANOTUBES                CNTs + PROBE ENZYMES      ...
Enhanced Nano-Bio-Sensing           RANDOMLY ORIENTED              VERTICAL                   BENT                        ...
Increased sensitivity~ 7.5 times more  Sensor sensitivity is enhanced by    nano-structuring the electrodes   15
Single/multiple target sensing Extending or arraying the probes    Proximity and interference of molecules    Separate ...
Platform design challenges Design modular platform that can be adapted to    Single/multiple targets Parametrize compon...
Block diagram of the Biosensing Platform                                           18
First Block     Third Block                                        1.525 mmSecond                         I/F Block       ...
Energy & data transmission                            Z(load)Power consumption vs. complexity                             ...
Energy & data transmission                             21
Prototype for in vivo remote monitoring                      LéandreBolomey, PhD. Thesis, EPFL                            ...
Glucose Monitoring (CNT+GOD)                               24
Lactate Remote Monitoring (CNT+LOD)                                 25
ATP Monitoring (CNT+GOD+Hexokinase)                         -700                                    Sensitivity = 34.2 pA ...
Performance of biosensors                            27
Conclusions Medical implants are an important testbed for  advanced electronic and sensor design Specific issues relate ...
Thank you PhD Students1.    Jacopo Olivo2.    Sara Ghoreishizadeh3.    Irene Taurino4.    EnverGürhan Kilinç5.    Giulia S...
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I-ironic

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  • It has been shown that administration of ATP at micro-molar concentrations can block tumor growth18-20. A possible application of our sensor, which is sensitive to micro-molar concentrations, is the monitoring of ATP in tumors: ensuring constant control of ATP concentration may represent a tool to personalize the anticancer therapy, helping to minimize the side effects coming from over-dosage of the compound, and to establish the optimal amount for the maximum therapeutic effect.
  • I-ironic

    1. 1. G. De Micheli,Q. Huang, L. Thoeny-Meyer, Y. Leblebici, C. Dehollain, F. Grassi, S. CarraraImplantable/Wearable System for on-line Monitoring of Human Metabolic Conditions (Implantable-IRONIC)
    2. 2. Implanted devices for monitoring In/Out tubing Almost only for diabetes A. Menarini Diagnostics, Florence Almost only for glucoseGlucoDay® and GlucoMenDay® consist of a micro-pump and a biosensor coupled to a micro-dialysis system 4
    3. 3. Target objectiveCylinder: about 2 mm in diameter and below 20 mm in length Fully implanted system with sensors, electronics and transmission 5
    4. 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. 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. 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. 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. 8. Cytochromes for biosensors 11
    9. 9. Electrode nanostructure 12
    10. 10. Enhanced Nano-Bio-Sensing BARE ELECTRODE CARBON NANOTUBES CNTs + PROBE ENZYMES 13
    11. 11. Enhanced Nano-Bio-Sensing RANDOMLY ORIENTED VERTICAL BENT 14
    12. 12. Increased sensitivity~ 7.5 times more Sensor sensitivity is enhanced by nano-structuring the electrodes 15
    13. 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. 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. 15. Block diagram of the Biosensing Platform 18
    16. 16. First Block Third Block 1.525 mmSecond I/F Block converter Ramp generator 1.525 mm
    17. 17. Energy & data transmission Z(load)Power consumption vs. complexity 20
    18. 18. Energy & data transmission 21
    19. 19. Prototype for in vivo remote monitoring LéandreBolomey, PhD. Thesis, EPFL 22
    20. 20. Glucose Monitoring (CNT+GOD) 24
    21. 21. Lactate Remote Monitoring (CNT+LOD) 25
    22. 22. ATP Monitoring (CNT+GOD+Hexokinase) -700 Sensitivity = 34.2 pA / M mm2 -600 Detection limit 346 μMcurrent 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. 23. Performance of biosensors 27
    24. 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. 25. Thank you PhD Students1. Jacopo Olivo2. Sara Ghoreishizadeh3. Irene Taurino4. EnverGürhan Kilinç5. Giulia Siciliano6. Roger Ulrich Scientists and Collaborators:7. Tom Kleier 1. Thomas Burger8. Beat Muheim 2. Michele Proietti9. Michael Fairhead 3. Renate Reiss10. Michael Richter 4. Thomas Ramsauer 5. Frank Gürkaynak 29

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