Fabrication of a large area flexible active microelectrode array with more than 1000 recording electrodes
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1
Hochschule Furtwangen, Germany
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2
Natural and Medical Sciences Institute, Germany
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3
Mannheim University of Applied Sciences, Germany
Motivation
Microelectrode arrays (MEAs) not only allow the examination of tissue in vitro, they can also build an in vivo interface between the nervous system and technical systems [1, 2]. The investigation of bioelectrical systems in the body, as well as the stimulation of nerves using electrodes provide new insights in the functioning of the body and provide new therapy possibilities (“electroceuticals”) [3].
Currently there are two main types of MEAs – passive and active. Passive MEAs contain electrodes firmly connected to a conducting track limiting the electrode density and the number of electrodes. Active MEAs based on CMOS-chips allow high electrode densities but are limited to small areas and are rigid [4].
The project Neuro-Flexarray aims for a new MEA closing the gap between these two types building a hybrid type MEA: the Neuroflexarray (NFA).
Materials and Methods
A flexible MEA with more than 1000 recording electrodes is formed by integrating an array of equal square-cut CMOS-dies with an edge length of only 250 µm into a flexible polymer foil.
The applied chip is developed within the project and contains a single 2-stage amplifier, a digital multiplexing unit and several switches. Herein the signals of a cluster of 25 electrodes are multiplexed, amplified and exported to a single wire thus reducing the number of output lines compared to a passive MEA. The size of the complete MEA may be scaled by adding further clusters. The pitch of the chips on the flexible substrate is 1140 µm preserving the flexibility of the whole array.
The CMOS chip has been developed in a CMOS 350 nm technology and features low power consumption (< 300 µW), low input referred noise (< 10 μVrms) and a signal amplification of 25 (28 dB).
The 2-stage operational amplifier has an open loop gain exceeding 100 dB and a gain-bandwidth product of 10 MHz – high enough to support the multiplexing with 10,000 cycles per second for 25 electrodes per cluster. The high open loop gain of the amplifier ensures high Common Mode Rejection (CMRR) and Power Supply Rejection Ratios (PSRR).
The fabrication process of the array was developed using non-functional die-dummies consisting of silicon wafer with aluminum contact areas on top. It starts with a selective transfer printing step where all dies for one array are transferred in a single step, by collecting every third die of each row and column by a stamp. Therefore the distance between neighboring dies is increased and the precision of die placement on the wafer is preserved. Afterwards the complete array is transferred face down to another substrate. Subsequently the structure is poured in PDMS. Hereafter another glass substrate is placed on top. Spacers guarantee the plane-parallel alignment of the two substrates. The first substrate is removed and the surface cleaned resulting in a flat topology allowing the use of photolithographic fabrication processes. Two layers of conducting tracks are then formed connecting the dies and forming the electrodes. Parylene C is used as insulator between the metal layers (see Figure 1).
Results and Discussion
The transfer printing process at the beginning shows perfect selectivity and almost 100% yield. At the edges of the dies, the PDMS exhibits a topography in the range of 20 µm in height, while the height of the die-dummies is 210 µm.
The contact pitch on the die surfaces is 40 µm. In order to allow the alignment of a photomask on the array the process is based on the conservation of the relative positions of all dies of an array throughout the whole process.
It showed that deviations in the relative positions occurred only in the first process steps (separation and transfer printing) and were below 20 µm for most dies of an array.
The first photomask for opening the parylene C passivation on top of the contacts of the dies could successfully be aligned on top of an array of die-dummies. Overlap between openings in the passivation on the die contacts has been reached for almost all dies of an array. However, this overlap is only small for most die-dummies as there is a slight shift of relative die positions (see Figure 2).
The transfer printing process described above allows a dense and thus cost efficient fabrication on wafers.
Conclusion and Outlook
A process for the fabrication of a new kind of flexible active microelectrode array has been developed using nonfunctional dies, while the functional die has been developed. These ASICs are planned to be available in summer 2018 so that functional Neuroflexarrays can be build. Simulations and measurements of the electronic chip show that amplifying and multiplexing is possible using a very small die area. An array of potentially 49 dies will result in 1225 electrodes with a pitch of 228 µm. This approach is suitable for further increase of the number of electrodes.
Figure Legend
Figure 1: Schematic principle of the fabrication process: The dies are separated using wafer dicing (1) and then transferred to a sugar coated substrate using a PDMS-stamp (2). The array is then turned upside down by transferring it to a shellac coated substrate (3). The array is then poured in PDMS and the shellac removed leaving a flat surface (4). Two layers of conducting tracks are formed on top using photolithography and parylene C as insulating material (5). Finally, the flexible array is released from its handling substrate (6).
Figure 2: Picture of six embedded die-dummies with patterned photoresist (round openings) on top. The little square contacts of the die have a size of (15 µm)² size and a pitch of 40 µm.
Acknowledgements
The authors acknowledge financial support via the project Neuro-Flexarray (Project no. 13FH031IB5 and 13FH03IA5) funded by the German Federal Ministry of Education and Research (BMBF).
References
[1] Spira, Micha E., and Aviad Hai. "Multi-electrode array technologies for neuroscience and cardiology." Nature nanotechnology 8.2 (2013): 83.
[2] Rubehn, Birthe, et al. "A MEMS-based flexible multichannel ECoG-electrode array." Journal of neural engineering 6.3 (2009): 036003.
[3] Famm, Kristoffer, et al. "Drug discovery: a jump-start for electroceuticals." Nature 496.7444 (2013): 159.
[4] Frey, Urs, et al. "Cell recordings with a CMOS high-density microelectrode array." Engineering in Medicine and Biology Society, 2007. EMBS 2007. 29th Annual International Conference of the IEEE. IEEE, 2007.
Keywords:
active MEA,
flexible,
chip in foil,
Bioamplifier,
CMOS-MEAs,
mesomanufacturing
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Poster Presentation
Topic:
Microelectrode Array Technology
Citation:
Heid
A,
Camoleze De Andrade
M,
Von Metzen
R,
Giehl
J and
Bucher
V
(2019). Fabrication of a large area flexible active microelectrode array with more than 1000 recording electrodes.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00040
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Received:
16 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Mr. Andreas Heid, Hochschule Furtwangen, Furtwangen im Schwarzwald, Germany, andreas.heid@hs-furtwangen.de