Thin-film transistors (TFTs) are the fundamental building blocks for the rapidly growing field of macroelectronics. The use of plastic substrates is also increasing in importance owing to their light weight, flexibility, shock resistance and low cost. Current polycrystalline-Si TFT technology is difficult to implement on plastics because of the high process temperatures required. Amorphous-Si and organic semiconductor TFTs, which can be processed at lower temperatures, but are limited by poor carrier mobility. As a result, applications that require even modest computation, control or communication functions on plastics cannot be addressed by existing TFT technology. Alternative semiconductor materials that could form TFTs with performance comparable to or better than polycrystalline or single-crystal Si, and which can be processed at low temperatures over large-area plastic substrates, should not only improve the existing technologies, but also enable new applications in flexible, wearable and disposable electronics. Here we report the fabrication of TFTs using oriented Si nanowire thin films or CdS nanoribbons as semiconducting channels. We show that high-performance TFTs can be produced on various substrates, including plastics, using a low-temperature assembly process. Our approach is general to a broad range of materials including high-mobility materials (such as InAs or InP).

A silicon-based device, dubbed a microphysiometer, can be used to detect and monitor the response of cells to a variety of chemical substances, especially ligands for specific plasma membrane receptors. The microphysiometer measures the rate of proton excretion from 10(4) to 10(6) cells. This article gives an overview of experiments currently being carried out with this instrument with emphasis on receptors with seven transmembrane helices and tyrosine kinase receptors. As a scientific instrument, the microphysiometer can be thought of as serving two distinct functions. In terms of detecting specific molecules, selected biological cells in this instrument serve as detectors and amplifiers. The microphysiometer can also investigate cell function and biochemistry. A major application of this instrument may prove to be screening for new receptor ligands. In this respect, the microphysiometer appears to offer significant advantages over other techniques.

Numerous biochemical reactions can be measured potentiometrically through changes in pH, redox potential, or transmembrane potential. An alternating photocurrent through an electrolyte-insulator-semiconductor interface provides a highly sensitive means to measure such potential changes. A spatially selectable photoresponse permits the determination of a multiplicity of chemical events with a single semiconductor device.

Cellular metabolism is affected by many factors in a cell's environment. Given a sufficiently sensitive method for measuring cellular metabolic rates, it should be possible to detect a wide variety of chemical and physical stimuli. A biosensor has been constructed in which living cells are confined to a flow chamber in which a potentiometric sensor continually measures the rate of production of acidic metabolites. Exploratory studies demonstrate several applications of the device in basic science and technology.

Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.

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Activation of 8-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular metabolic rates. Changes in cell metabolism were monitored continuously with a previously described silicon-based microphysiometer that detects small changes in extracellular pH. The amplitude and kinetics of the metabolic changes depend upon several factors including pretreatment of the cells prior to receptor stimulation, the dose of hormone/neurotransmitter used, and the receptor comple- Recent work has shown that the metabolic rates of small samples of living cells can be measured by using a semiconductor-based instrument, the silicon microphysiometer, to detect the rate of excretion of acidic metabolic products (1). These studies revealed the expected qualitative effects of various nonspecific toxic chemicals on the metabolic rates of a variety of cultured cells. In addition, epidermal growth factor (EGF) was shown to affect the metabolic rates of cells containing the EGF receptor. This is not unexpected because increases in cellular glycolytic rates in response to insulin and EGF have been reported and thought to be associated with initiation of a transition of the cells from a dormant (nonproliferating) state to a proliferative state (2).The ability to measure cellular responses to receptorligand interactions on a time scale of minutes suggests that the silicon microphysiometer may be particularly useful for screening new therapeutic drugs. Thus, a major objective of the work reported here was to evaluate this approach as a practical and general method of detecting functional ligandreceptor interactions. To address this question in part, we evaluated changes in cellular metabolic rates elicited by stimulation of receptors that are not normally associated with mitogenesis.We investigated the effects of two receptors known to mediate their biochemical actions through guanine nucleotide-binding proteins (G proteins), P2-adrenergic and ml muscarinic acetylcholine receptors. These are representative of the major neuroreceptor classes in the sympathetic and parasympathetic nervous systems. Although there are many cell lines available that endogenously contain such receptors, we chose to use Chinese hamster ovary (CHO) cells and murine B-82 cells transfected with the genes encoding each of these receptors. This approach provides a particularly welldefined experimental system and permits the study of the same receptor in different cell types or different receptors in the same cells. MATERIALS AND METHODSMaterials. Unless otherwise indicated, chemicals were obtained from Sigma and culture media from GIBCO. Transforming growth factor a (TGF-a) was a gift from Rick Harkins (Triton Biosciences, Alameda, CA). EGF was purchased from Clonetics (San Diego), and the anti-EGF antibody was from Collaborative Research.Keratinocytes. Normal human epidermal keratinocytes were obtained from Clonetics. The cells were cultured i...