45 research outputs found

    A 16×16 CMOS proton camera array for direct extracellular imaging of hydrogen-ion activity

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    Over the past twenty-five years, silicon CMOS technology has firmly established itself as the dominant platform in the microelectronics industry. This has resulted in many recent initiatives to fabricate CMOS-based microelectrodes for the stimulation and recording of electrical activity of neurons. CMOS technology offers the potential for monolithic integration of sensors and electronics and it serves as an appropriate platform to facilitate the integration of large arrays of sensors into a small geometry. The extracellular pH of a cell culture is a particularly important indicator of global cellular metabolism, but up until now, this property has typically been measured with invasive and expensive techniques such as miniaturized glass microelectrodes, fluorescent ratio imaging microscopy and magnetic resonance spectroscopy. CMOS provides a scalable, low cost, mass manufacturing platform, and offers the potential to develop sensor arrays that can perform non-invasive and long term imaging on cultured cells. In this paper, we present the first 16x16 proton camera array for direct imaging of the hydrogen-ion activity of cell cultures grown in vitro. The proton camera is based on a single-chip ion-sensitive field-effect transistor (ISFET) sensor array technology that can be implemented using a standard commercial CMOS process

    Mechanical gradient cues for guided cell motility and control of cell behavior on uniform substrates

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    A novel method for the fabrication and the use of simple uniform poly(dimethylsiloxane) PDMS substrates for controlling cell motility by a mechanical gradient is reported. The substrate is fabricated in PDMS using soft lithography and consists of a soft membrane suspended on top of a patterned PDMS substrate. The difference in the gradient stiffness is related to the underlying pattern. It is shown experimentally that these uniform substrates can modulate the response of cell motility, thus enabling patterning on the surfaces with precise cell motility. Because of the uniformity of the substrate, cells can spread equally and a directional movement to stiffer regions is clearly observed. Varying the geometry underlying the membrane, cell patterning and movement can be quantitatively characterized. This procedure is capable of controlling cell motility with high fidelity over large substrate areas. The most significant advance embodied in this method is that it offers the use of mechanical features to control cell adhesion and not topographical or chemical variations, which has not been reported so far. This modulation of the response of cell motility will be useful for the design and fabrication of advanced planar and 3D biological assemblies suitable for applications in the field of biotechnology and for tissue-engineering purposes

    A large transistor-based sensor array chip for direct extracellular imaging

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    This paper describes the development and evaluation of a large transistor-based sensor array chip for direct extracellular imaging. All of the sensors and electronics are designed and fabricated using an unmodified CMOS process. The sensor array chip consists of a 16×16 pixel array of ISFETs along with signal acquisition and readout circuitry. Each ISFET employs a floating gate electrode structure and uses the passivation layer as a pH sensitive membrane. The chip layout is optimised so that the surface topography allows cultured cells to be grown directly above the pixel array. On return from the foundry, a double layer of SU-8 photoresist is used to provide a biocompatible and waterproof package for the chip. An elastomer-based microfluidic chamber is fabricated and integrated for conducting long term cell culture experiments. The performance of the chip is evaluated using an electrolyte and a well-established confluent cell line. The fabricated circuit provides a linear operating range of 2.5 V that allows each ISFET to operate as a pH sensor in the array. The ISFETs have a threshold voltage of − 1.5 V and a sensitivity of 46 mV/pH.<p></p&gt

    Interaction of animal cells with ordered nanotopography

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