Chemical sensors based on individual single-walled carbon nanotubes (SWNTs) are demonstrated. Upon exposure to gaseous molecules such as NO 2 or NH 3 , the electrical resistance of a semiconducting SWNT is found to dramatically increase or decrease. This serves as the basis for nanotube molecular sensors. The nanotube sensors exhibit a fast response and a substantially higher sensitivity than that of existing solid-state sensors at room temperature. Sensor reversibility is achieved by slow recovery under ambient conditions or by heating to high temperatures. The interactions between molecular species and SWNTs and the mechanisms of molecular sensing with nanotube molecular wires are investigated.

https://science.sciencemag.org/content/sci/287/5453/622.full.pdf

Nanotube molecular wires as chemical sensors

This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on surface, where the array comprising more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface, the density of the different oligonucleotides is greater than about 60 different oligonucleotides per 1 cm2, and the oligonucleotide probes are complementary to the RNA transcripts or nucleic acids derived from the RNA transcripts; and quantifying the hybridized nucleic acids in the array.

Expression monitoring by hybridization to high density oligonucleotide arrays

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

/pdf/microfluidics-fluid-physics-at-the-nanoliter-scale-4bpahtd8qa.pdf

Microfluidics: Fluid physics at the nanoliter scale

High-density microfluidic chips contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large scale integration (LSI). A component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. These integrated microfluidic networks can be used to construct a variety of highly complex microfluidic devices, for example the microfluidic analog of a comparator array, and a microfluidic memory storage device resembling electronic random access memories.

https://science.sciencemag.org/content/sci/298/5593/580.full.pdf

Microfluidic large scale integration

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.

https://science.sciencemag.org/content/sci/257/5078/1906.full.pdf

The cytosensor microphysiometer: biological applications of silicon technology

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.

https://science.sciencemag.org/content/sci/246/4927/243.full.pdf

Detection of cell-affecting agents with a silicon biosensor

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.

Electrokinetically Controlled Microfluidic Analysis Systems

PRINCIPLES OF THE LIGHT-ADDRESSABLE POTENTIOMETRIC SENSOR 88 Measurement of pH 89 The Photoeffect 90 Light Addressability 93 Measurement of Other Chemical Species 93 THE LAPS AS A SENSOR IN AN ANALYTICAL SYSTEM 94 Electrical Measurement of Phospholipid Membranes 94 Discrete Sensor Arrays 94 LAPS as an Imaging Sensor 94 Microvolume Systems 95 The Sensor as a Structural Element of Analytical Systems 96 Data Analysis in LAPS Systems 96 APPLICATIONS FOR BIOCHEMICAL ASSAYS 98 Measurement of Enzyme Substrates and lnhibitors 98 Enzyme-Linked lmmunoassays 98 APPLICATIONS FOR CELL-BASED BIOASSAYS: THE MICROPHYSIOMETER 102 Biological Basis 102 Instrumental Characteristics 102 Applications of Microphysiometry 105 Prospects 108 CONCLUDING PERSPECTIVE 109

J. W. Parce

Papers

The cytosensor microphysiometer: biological applications of silicon technology

Detection of cell-affecting agents with a silicon biosensor

Electrokinetically Controlled Microfluidic Analysis Systems

The Light-Addressable Potentiometric Sensor: Principles and Biological Applications

Biosensors based on the energy metabolism of living cells: The physical chemistry and cell biology of extracellular acidification