High Resolution Neuro-Electronic Interface System for Electrophysiological Experiments

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1 High Resolution Neuro-Electronic Interface System for Electrophysiological Experiments Research presentation by Neil Joye (LSM, EPFL) on the 20 th June 2007

2 Content Introduction State of the Art 3D tip electrodes Current work MEA manufacturing Modeling Packaging Future work CMOS design and CMOS postprocessing

3 Introduction Goal of the work Built very high-density Microelectrode Arrays (MEAs) with CMOS processing on chip for recording and stimulating electrical activity in neuron cultures. In collaboration with the Laboratory of Neural Microcircuitry (LNMC) of the Brain Mind Institute MEA Neuron Neuron Culture Sensors / Actuators PC CMOS circuit Processing (Amplification, Addressing, ADC, )

4 Introduction Extracellular voltage that is sensed is 3-4 orders of magnitude smaller than the intracellular voltage (action potential) Main challenge High spatial resolution Small electrode size High electrode impedance High SNR

5 State of the Art (1) Prof. Hierlemann s group (ETHZ) 1 8 x 16 = 128 electrodes Techno CMOS 0.6 µm Sensor diameter = µm Pitch = µm Input noise = 17 µvrms (with 20 µm diameter electrodes) Advantages Able to record and stimulate A lot of signal processing is already done at the pixel level Low noise Disadvantages Low spatial resolution (neuron size around 10 µm) 1 F. Heer et al., Biosensors and Bioelectronics, 2007

6 State of the Art (1) F. Heer et al., JSSC, 2006 F. Heer et al., Biosensors and Bioelectronics, 2007

7 State of the Art (1) D.A Wagenaar et al., Journal of Neuroscience, 2005

8 State of the Art (1) F. Heer et al., Biosensors and Bioelectronics, 2007

9 State of the Art (1) F. Heer et al., Biosensors and Bioelectronics, 2007

10 State of the Art (2) SAMLAB, IMT, University of Neuchatel 2 64 x 64 = electrodes Techno CMOS 0.5 µm Sensor size = 20 x 20 µm 2 Pitch = 40 µm Input noise = 80 µvrms Advantages Higher spatial resolution (only 8 transistors per pixel) Disadvantages Higher input noise 2 L. Berdondini et al., Biosensors and Bioelectronics, 2005

11 State of the Art (2) L. Berdondini et al., Biosensors and Bioelectronics, 2005

12 3D tip electrodes Goal Decrease the distance electrode-neuron in order to improve the neuron-electrode coupling This assumption is currently being tested and proved theoretically with an electrical model experimentally with electrophysiological measurements

13 Current work A first generation of MEA is being manufactured at the moment in CMI No CMOS processing is done on these chips (future work) 3 versions are planed to be manufactured MEA Neuron Neuron Culture Sensors / Actuators PC CMOS circuit Processing (Amplification, Addressing, ADC, )

14 MEA version-1 Planar electrodes 6 x 6 = 64 electrodes Sensor size 2 20 µm Pixel size 4 40 µm Goal Compare measurements with different sensor and pixel sizes Results will be compared with the one obtained from 3D tip electrodes (version-2) Improve the neuron-sensor model that is being developed

15 MEA version-1

MEA version-2 3D tip electrodes Output wiring done on the surface Goal Study the manufacturing of the 3D tip electrodes (size, shape, process characteristics, etc.

16 MEA version-2 3D tip electrodes Output wiring done on the surface Goal Study the manufacturing of the 3D tip electrodes (size, shape, process characteristics, etc.) Measure electrical and biological characteristics of these arrays Establish a controlled and straightforward manufacturing process for these 3D tip electrode arrays

17 MEA version-2

18 MEA version-2

19 MEA version-2

20 MEA version-2 Challenges We are approaching the size limit for the 3D tip electrodes manufacturing

21 MEA version-3 3D tip electrode arrays with output wiring on 2 metal layers Biological measurements Compare with planar electrodes Compare with simulations obtained using developed model Improvement of the model to be made if necessary

22 Neuron-Sensor Model (1) Based on Hodgkin-Huxley model A model of the interaction between neurons and planar electrodes is being developed Simulations will be compared with biological and electrical measurements in order to improve the model I. Schoen and P. Fromherz, Biophysical Journal, 2007

23 Neuron-Sensor Model (2) For the 3D tip electrodes, a lower level model is been developed Lower level Electrical field Our model will be used for electrodes which are one order of magnitude smaller than the one shown on this graph M.O. Heuschkel el al., Journal of Neuroscience Methods, 2002

24 Neuron-Sensor Model (2) Current work using FEMLAB simulations

25 Neuron-Sensor Model (2) Current flow from neuron to electrode (recording of an action potential) Planar electrode 3D tip electrode

26 Neuron-Sensor Model (2) Electrical field simulation

27 Neuron-Sensor Model (2) Voltage potential simulation

28 Neuron-Sensor Model (2) Current and future work Improving the model Using the reel action potential waveform instead of a constant voltage Simulating the current flow from electrode to neuron (stimulation of an action potential) Simulating the interaction between a neuron culture and an electrode array Final goal of the model Find the optimum electrode array Size, shape, pitch, etc.

Bond wires must not be pulled off, either by thermal expansion of by swelling of the

29 Packaging PCB must be compatible with Multi Channel Systems equipment (used in LNMC) Packaging must protect the bond wires from being attacked by physiological solutions Bond wires must not be pulled off, either by thermal expansion of by swelling of the material due to liquid absorption In future work, alternatives to wire bonding will be investigated

30 Future work (CMOS) MEA Neuron Neuron Culture Sensors / Actuators PC CMOS circuit Processing (Amplification, Addressing, ADC, ) A CMOS chip is expected to be taped out during this fall Different functionalities will be implemented on this integrated circuit Amplification stage Filtering Addressing of each sensor Then, post-fabrication of electrodes on the surface of the chip is expected to be done next spring

A 256-by-256 CMOS Microelectrode Array for Extracellular Neural Stimulation of Acute Brain Slices. Columbia University, New York, NY

A 256-by-256 CMOS Microelectrode Array for Extracellular Neural Stimulation of Acute Brain Slices Na Lei 1, K L Shepard 1, Brendon O Watson 2, Jason N MacLean 2, Rafael Yuste 2 1 Department of Electrical