1. High Spatial Resolution 3D Probes for Neurobiology Applications PSD Conference ’08 2 nd September Deborah E. Gunning EPSRC Overseas Life Science Interface Postdoctoral Fellow K. Mathieson (U of Glasgow), A.M. Litke (UC Santa Cruz)

2. Outline: Background and motivation Why are position sensitive detection probes needed to study neuronal behaviour? Arrays: Design requirements Developed fabrication process Characterisation Mechanical Electrical Next step Conclusions and future work

3. Background Traditionally: amplification electrode neuron signal from neuron Ref: Hubel and Wiesel, Nobel prize winners 1981 physiological saline solution neural tissue microelectrode array amplification More recently: planar electrodes Ref: D.Gunning et al., Nuclear Instruments and Methods in Physics research, 2005. Developing: physiological saline solution neural tissue bed-of-nails array amplification probes Improve electrode/cell contact. Probe a 3-D distribution of cells such as found in brain slices

4. Background Utah Neural Array: 1.5mm 400  m Michigan Neural Probes: 2mm 500  m Current bed-of-nails devices: LOW SPATIAL RESOLUTION!

5. Previous studies with planar arrays have shown that 30-60  m provides excellent coverage of cells Design requirements: Unprecedented dimensions: Nanofabricated on silicon wafers 61 hexagonally close packed electrodes Up to 200  m high spikes (variable) <10  m diameter tips 60  m inter-electrode spacing Bed-of-nails ~ design <10  m 200  m 60  m

6. Existing 61 channel readout system –Extensive and successful use with planar microelectrode arrays Bed-of-nails compatible with system –Wire bonded in to custom made daughter board Specifications: –Bandpass filter 50 – 2000 Hz –Noise 5  Vrms –Sampling rate 20 kHz W. Dabrowski et al., Biosensors and Bioelectronics 19, 2004 Bed-of-nails ~ readout system array placed here

7. Bed-of-nails ~ fabrication 1. DRI etch holes in silicon 2. Conformally coat with oxide and tungsten 3. Etch tungsten - isolate electrodes electrically 4. Deposit and etch polySi to expose W 5. Deposit and etch 1um aluminium 6. Protect holes and turn wafer upside down 7. Half etch oxide covered tip 8. Etch more Si - defining length of needles

8. Bed-of-nails ~ fabrication results

9. Bed-of-nails ~ daughter board Side 1: Bed-of-nails wire bonded to daughter board Side 2: Chamber glued with grounding platinum wire Daughter board fixed to 61-channel readout system needles wire bonds glass chamber daughter board Side 1 Side 2

10. Electrical tests Tungsten tip needles – very high impedance (~5 M  ) Need ~300 k  at 1 kHz Lower impedance by platinising: Apply current to electrode through platinic chloride solution Tungsten electroplated with “platinum black” Granular platinum formation increases surface area Preliminary result: 565 k  at 1 kHz

11. Next step Placement of daughter board/bed-of-nails into 61-channel system Characterise: –Noise: noise compares with 61-channel system (8  Vrms in saline) signal improvement on 61-channel system (>200  V) signal to noise improvement Recordings from: –Mouse retina Dr. A. Sher, Dr. D. Feldheim at UC Santa Cruz More comprehensive study of retina –Cortical slices Dr. J. Beggs, Indiana University Further study neuronal firing behaviour and phenomena

12. Conclusion and future work Unique array developed to study neural networks Unprecedented dimensions Mechanically stable Promising electrical characteristics Future: Arrays of longer needles (up to 500  m) Arrays of multi-length needles Proof of principle: Arrays on flexible substrates In-vivo studies