Agnès Tixier-Mita

Review on thin-film transistor technology, its applications, and possible new applications to biological cells

This paper presents a review on state-of-the-art of thin-film transistor (TFT) technology and its wide range of applications, not only in liquid crystal displays (TFT-LCDs), but also in sensing devices. The history of the evolution of the technology is first given. Then the standard applications of TFT-LCDs, and X-ray detectors, followed by state-of-the-art applications in the field of chemical and biochemical sensing are presented. TFT technology allows the fabrication of dense arrays of independent and transparent microelectrodes on large glass substrates. The potential of these devices as electrical substrates for biological cell applications is then described. The possibility of using TFT array substrates as new tools for electrical experiments on biological cells has been investigated for the first time by our group. Dielectrophoresis experiments and impedance measurements on yeast cells are presented here. Their promising results open the door towards new applications of TFT technology.

TFT display panel technology as a base for biological cells electrical manipulation - application to dielectrophoresis

This paper reports for the first time the use of TFT (Thin Film Transistor) technology of display panels for biological cells electrical manipulation. This technology allows to have high density distributed transparent micro-electrodes, independently controllable, covering centimeter-size glass substrates. This technology is much superior to usual micro-technology used for Multielectrode Arrays (MEAs), which allows only millimeter size surface with micro-electrodes, and with a limited number of 64 micro-electrodes maximum. The chosen application, to demonstrate the capability of such technology, is dielectrophoresis on micro-beads and yeast cells.

A Balanced-SeeSaw MEMS swing probe for vertical profilometry of deep micro structures

An actuator-integrated MEMS needle probe is improved to measure vertical surface profile of narrow and deep test structures such as microholes and trenches. A newly developed surface scanning method, called ¿swing probing¿, can reduce the measurable feature size by factor of up to eight (i.e. from 40 ¿m down to 5 ¿m for 50¿m-deep trenches, and down to 25 ¿m for 1 mm-deep ones) as compared to traditional ¿slide probing¿. The improvement is due to the new ¿Balanced-SeeSaw¿ probe design that guarantees rotational movement without wobbling as well as sensitivity increase. Since the design is highly scalable, the probe can further reduce target feature size as well as measurement resolution thus may enlarge the application field of such surface quality assessment technology to MEMS process test structure monitoring.

To Place Cells as an Array Using Aspiration Technique

Thousands of cells are simultaneously aligned in array in grace of a silicon micro-strainer. The cells alignment was performed in few seconds with sub-micron precision.

A simple, robust and controllable nano-structures fabrication technique using standard silicon wafers

We succeeded to realize nano-structures using standard {100} silicon wafers and anisotropic etching; this technique makes use of the low etching rate in TMAH of {111} planes or silicon, in comparison to {100} planes, to adjust the nanometric dimensions of the structures. No sub-micron lithography is required in this technique: it is compatible with normal UV photolithography. Neither complicated process steps are required: a succession of oxidation, oxide patterning and anisotropic etching only are needed. Nano-holes and nano-wires were made using this technique and possible applications of the structures are described for two BIO-MEMS projects.

In vitro cyto-biocompatibility study of thin-film transistors substrates using an organotypic culture method

Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field of displays. However, the structure of these devices presents interest not only in that field, but also for biomedical applications. One of the key components, called here TFT substrate, is a glass substrate with a dense and large array of thousands of transparent micro-electrodes that can be considered as a large scale multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro electrical investigations on neurons and brain, allowing excitation, registration, and recording of their activity. However, the range of application of conventional multi-electrode array(s) is usually limited to some tens of cells in a homogeneous cell culture, because of a small area, small number and a low density of the micro-electrodes. TFT substrates do not have these limitations and the authors are currently studying the possibility to use TFT substrates as new tools for in vitro electrical investigation on tissues and organoids. In this respect, experiments to determine the cyto-biocompatibility of TFT substrates with tissues were conducted and are presented in this study. The investigation was performed using an organotypic culture method with explants of brain and liver tissues of chick embryos. The results in term of morphology, cell migration, cell density and adhesion were compared with the results from Thermanox®, a conventional plastic for cell culture, and with polydimethylsiloxane, a hydrophobic silicone. The results with TFT substrates showed similar results as for the Thermanox®, despite the TFT hydrophobicity. TFT substrates have a weak cell adhesion and promote cell migration similarly to Thermanox®. It could be concluded that the TFT substrates are cyto-biocompatible with the two studied organs.

Transparent Thin Film Transistor electrode array for real-time Electrical Impedance Spectroscopy of cell cultures

We present the usage of an optically transparent Thin Film Transistor (TFT) electrode array to perform arbitrarily spatially confined electrical characterizations of a cell culture. These arrays are a mature technology commonly used in Liquid Crystal Displays, and manufacturable on a scale of up to square meters. Electrical characterization allows one to detect not only changes of concentration of cells in cultures, but also the components and state of the cells in the culture. Unfortunately these characterizations are extremely dependent on the positioning of the cell with respect to the electrode and as such require specialized conditions or trapping mechanisms to garner consistent data. By utilizing a large TFT electrode array we are able to get around this by providing a stochastic aggregate throughout the array that provides consistent metrics for the culture. It has been verified that this device is capable of electrically detecting changes in the living and dead cell populations of yeast (S. Cerevisiae).

Compressively-stressed test structures for opaque micro-stmctures releasing visualization

Stressed test structures have been fabricated to precisely determine the releasing time of low stress and opaque MEMS. These test structures will deform as soon as they are released, in contrast to low stress target structures that remain flat. Thanks to the test structures, it becomes possible to detect the releasing with an optical microscope.

Single crystal nanoresonators at 100 MHz fabricated by a simple batch process

Nanoresonators with resonant frequency until 100 MHz and with Q-factors until 15000 were realized in a single crystal <100> standard silicon wafer, using standard UV photolithography and anisotropic etching with TMAH. Their cross-section is triangular, with edges following <111> and <100> planes, and they are aligned along the {110} direction. While the resonant frequency decreases with the increase of the length, as expected, the Q factor shows quite different values between the two tested batch process. This is due to the connecting parts of the resonators to the bulk, which differs in the two batch process, with one giving more dissipation losses than the other one.

Gold functionalized nano-needles for angular protein movement visualization

We have investigated and compared various methods of fabricating silicon nano-needles of 100–200 nm in diameter and 1–2 µm in length for visualization of motor protein movement. Owing to their thin and long geometry, the needles are ideal to amplify and visualize angular movement. To enable highly localized protein attachment, a well-defined attachment point at one end of the needles was prepared. Fabrication by electron-beam lithography as well as by a highly parallel non-lithographic process were implemented and compared. Sensitive angular motion amplification was demonstrated by attachment of needles to F1 ATPase rotation motor proteins. In this report we characterize the fabrication processes, discuss the differences, and present the results of motor protein motion visualization.