Fabrication of CMOS Compatible Sub-micron Nails for On-chip Phagocytosis
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1009-U08-05
Fabrication of CMOS Compatible Sub-micron Nails for On-chip Phagocytosis Roeland Huys1, Carmen Bartic1, Bart Van Meerbergen1, Dries Braeken1, Josine Loo1, Kurt Winters1, Chang Chen1, S. Yitzchaik2, M. Spira3, J. Shappir4, and Gustaaf Borghs1 1 Bioelectronic Systems, IMEC, Kapeldreef 75, Heverlee, 3001, Belgium 2 Dept. of Inorganic & Analytical Chemistry, The Hebrew University of Jerusalem, Givat-Ram Campus, Jerusalem, 91904, Israel 3 Dept. of Neurobiology, The Hebrew University of Jerusalem, Givat-Ram Campus, Jerusalem, 91904, Israel 4 School of Applied Physics, The Hebrew University of Jerusalem, Givat-Ram Campus, Jerusalem, 91904, Israel
ABSTRACT Neuronal research requires to efficiently perform long-time experiments on large-scale neuronal networks in a minimally invasive way. Such experiments imply stimulation and measurements of electrical activity on a large number of neurons. This could be achieved by on-chip integration of actuators, sensors and readout electronics with dimensions comparable to the sizes of neurons. Integration of biosensors at this scale creates new challenges: the processing of the sensors must be compatible with state-of-the art CMOS technology, the system must be biocompatible, and the down-scaled technology imposes restrictions on the applicable stimulation voltages and increases the electrical noise. Recently it has been demonstrated that biological phenomena can be exploited in order to achieve the best coupling between cells and sub-micron scale electronics. Engulfment of submicron nail structures by the cell membrane minimizes the distance between the sensor and the cell [1], [2]. This paper presents two methods to produce nails with sizes from sub-micrometer to micrometer scales, on top of a CMOS chip. Prototype chips have been fabricated, and cells have been cultured to examine the in-vitro bio-compatibility of the chip. INTRODUCTION In the last decade, it became possible to develop chips with integrated microelectronics and biosensors. Such chips can be used in several bio-related applications, like in-vitro research of neurodegenerative diseases, drug screening, and prosthetic devices. Neurons have the property to generate electrical signals called action potentials. It has been shown that these signals can be captured by MOS-based transistors with the gate metal removed and replaced by the neurons attached directly onto the gate oxide [3], [4]. Small mammalian neurons are particularly relevant for the investigation of neurological diseases. Fabrication of biosensors that match mammalian neuronal sizes around 10µm has recently become possible thanks to the miniaturization of microelectronics. Furthermore, state-of the art chips for neuronelectronic interfacing allow the organization of such sensors in large high-density arrays. Although such arrays allow to address neurons in brain slices [5], [6], high signal-to-noise recordings from dissociated cells still remain a challenge. The advantages of microelectronics come with new challenges: the fabrication of the sens
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