An absorption detection approach for multiplexed capillary electrophoresis using a linear photodiode array

A novel absorption detection method for highly multiplexed capillary electrophoresis is presented for zone electrophoresis and for micellar electrokinetic chromatography. The approach involves the use of a linear photodiode array on which a capillary array is imaged by a camera lens. Either a tungsten lamp or a mercury lamp can be used as the light source such that all common wavelengths for absorption detection are accessible by simply interchanging narrow-band filters. Each capillary spans several diodes in the photodiode array for absorption measurements. Over 100 densely packed capillaries can be monitored by a single photodiode array element with 1024 diodes. The detection limit for rhodamine 6G for each capillary in the multiplexed array is ～1.8 × 10(-)(8) M injected (S/N = 2). The cross-talk between adjacent capillaries is less than 0.2%. Simultaneous analysis of 96 samples is demonstrated.     

Integrating waveguide biosensor

A capillary biosensor is demonstrated which uses the waveguiding properties of the capillary to integrate the signal over an increased surface area without simultaneously increasing the background noise from the detector. This biosensor achieves limits of detection of 30-50 pg/mL in immunoassays using a diode laser for excitation and a PMT for detection. This is approximately 2 orders of magnitude greater sensitivity than was achieved using the same immunoassay reagents in a fiber optic biosensor or a planar array biosensor. Two different approaches to using the capillaries as immunosensors are described, either of which could be adapted for multianalyte sensing.     

A simple method for the evaluation of microwave mixer diodes

A simple method is described for the evaluation of the various microwave mixer diodes which can be used in 9-GHz electron paramagnetic resonance (EPR) spectrometers using magnetic field modulation below 1 kHz. The advantage of this method over other methods is that it is optimized for EPR applications and determines the optimum operating conditions for each microwave diode. This method utilizes a microwave bridge with a reference arm with an attenuator to control the microwave bias power level, and a signal arm where the signal is attenuated, phase shifted, and modulated at the typical magnetic field modulation frequencies. The microwave power from the two arms is recombined and demodulated by the microwave diode. The output of the microwave diode is then recorded with various video loads, microwave bias power, and modulation frequencies. Measurements are performed to determine the effect of the preamplifier that followed the microwave diode on the signal-to-noise ratio (SNR). The recorded spectra are used to determine the SNR, the noise floor, and the 1/f corner frequency. Comparison of these factors for the different types of microwave diodes shows that some Schottky-barrier diodes have noise figures at 1 kHz that are as low as those for tunnel diodes     

High-density fiber-optic genosensor microsphere array capable of zeptomole detection limits

The detection limit of a fiber-optic microsensor array was investigated for simultaneous detection of multiple DNA sequences. A random array composed of oligonucleotide-functionalized 3.1-microm-diameter microspheres on the distal face of a 500-microm etched imaging fiber was monitored for binding to fluorescently labeled complementary DNA sequences. Inherent sensor redundancy in the microarray allows the use of multiple microspheres to increase the signal-to-noise ratio, further enhancing the detection capabilities. Specific hybridization was observed for each of three sequences in an array yielding a detection limit of 10(-21) mol (approximately 600 DNA molecules).     

Laser-induced fluorescence detection by liquid core waveguiding applied to DNA sequencing by capillary electrophoresis

A new laser-induced fluorescence detector for capillary electrophoresis (CE) is described. The detector is based on transverse illumination and collection of the emitted fluorescent light via total internal reflection along the separation capillary. The capillary is coated with a low refractive index fluoropolymer and serves as a liquid core waveguide (LCW). The emitted light is detected end-on with a CCD camera at the capillary exit. The observed detection limit for fluorescein is 2.7 pM (550 ymol) in the continuous-flow mode and 62 fM in the CE mode. The detector is applied to DNA sequencing. One-color G sequencing is performed with single-base resolution and signal-to-noise ratio approximately 250 for peaks around 500 bases. The signal-to-noise ratio is approximately 50 for peaks around 950 bases. Full four-color DNA sequencing is also demonstrated. The high sensitivity of the detector is suggested to partly be due to the efficient rejection of scattered laser light in the LCW. The concept should be highly suitable for capillary array detection.     

Signal-to-noise ratio in microelectrode-array-based electrochemical detectors

The signal-to-noise ratio at an electrode array depends on the electrode area, the perimeter-to-area ratio of the electroactive portion of the surface, the mass transfer coefficient of the analyte-electrode combination, the measurement bandwidth, and the sources and magnitudes of the noises. Simple models for chronoamperometry with an array in quiescent solution and for hydrodynamic current at an array in one wall of a rectangular conduit through which analyte-containing solution is following are given. Noises from seven sources, including environmental noises, are considered in a noise model. The signal and noise models are combined to yield a model for signal-to-noise ratio at array-based electrochemical detectors. There exists an optimum array density for a given area that depends on the noise power, noise resistance, the current density at a sparse array, and the current density at a solid electrode of the same area. Approximations that lead to simple expressions for the optimum electroactive area fraction and noise resistance lead to results that are in good agreement with more complex and less approximate calculations. Electrodes of millimeter dimensions consisting of about 1% active surface with electroactive "pieces" of micrometer dimensions are anticipated to yield detection limits of about 1 fmol injected into a typical packed-column liquid chromatograph. This corresponds to about 10(-10) M analyte in the detector and about an order of magnitude improvement over solid electrodes.     

Phase-sensitive fluorescence lifetime detection in capillary electrophoresis

A simple and highly sensitive fluorescence lifetime detection method for capillary electrophoresis has been introduced. The detection scheme is based on the integrated phase-sensitive fluorescence intensity. The integrative nature of the method results in high sensitivity of lifetime detection. The limit of detection is 7.8 amol of fluorescein injected, representing a 2 orders of magnitude improvement over the detection limits previously reported in the UV-visible region. Rayleigh scattering, Raman scattering, and background fluorescence can be effectively suppressed by setting the detector out of the phase from the background signal. Fluorescence background can be eliminated whether the fluorescence lifetime of the background is longer or shorter than the solute molecules of interest. The signal-to-noise ratio of measurements is optimized by varying the modulation frequency and the detector phase angle.     

Measurement of Moisture Content in Cardboard Bales by Microwave

In this work, a system for measuring moisture content in bundles of recycled cardboard sheets using microwaves is proposed and evaluated. For the development of this system, a microwave generator and an antenna tuned in the X-band were used. The detector system used was formed by a diode array point of contact. Calibration curves of moisture content in bales versus voltage in the array were obtained for two orientations or positions of the cardboard sheets in the sample bales. The results showed that the higher the moisture content, the lower the voltage is induced in the diodes. It was also observed that the attenuation of the microwave signal depends on the position of the cardboard sheets and that the measurement can be made in samples of bales with a maximum of 35% humidity, because on this percentage, the variation of voltage in the diode array is almost zero.     

Comparison of Hadamard transform and signal-averaged detection for microchannel electrophoresis

A Hadamard transform (HT) detection method for microchip capillary electrophoresis with laser-induced fluorescence and a charge-coupled device (CCD) is described and compared to signal-averaged detection. A low-noise CCD camera is used to image a section of a separation channel where each camera pixel can be thought of as a unique detector. For signal averaging, electropherograms corresponding to individual pixels can be averaged for improved S/N. HT detection is performed on each pixel electropherogram to generate a contour plot electropherogram. The multiple injections required for HT provides an enhancement at the cost of longer times for the pseudorandom injection sequences. A short sample injection length of 0.25 s is used to reduce the overall analysis time and improve sensitivity compared to previously published results. An injection sequence is performed on the microchip that is based on a cyclic S-matrix of 513 elements that generates an 8-fold improvement in S/N compared to a single injection. This spatially resolved HT detection method is also capable of performing a multicomponent separation. Signal-averaged HT and single-injection data are compared to experimental HT and single-injection results. The unique capabilities of each method are described.     

Shot-noise-limited dual-beam detector for atmospheric trace-gas monitoring with near-infrared diode lasers

A dual-beam detector is used to measure atmospheric trace species by differential absorption spectroscopy with commercial near-infrared InGaAs laser diodes. It is implemented on the Spectromètre à Diodes Laser Accordables, a balloonborne tunable diode laser spectrometer devoted to the in situ monitoring of CH(4) and H(2)O. The dual-beam detector is made of simple analogical subtractor circuits combined with InGaAs photodiodes. The detection strategy consists in taking the balanced analogical difference between the reference and the sample signals detected at the input and the output of an open optical multipass cell to apply the full dynamic range of the measurements (16 digits) to the weak molecular absorption information. The obtained sensitivity approaches the shot-noise limit. With a 56-m optical cell, the detection limit obtained when the spectra is recorded within 8 ms is ~10(-4) (expressed in absorbance units). The design and performances of both a simple substractor and an upgraded feedback substractor circuit are discussed with regard to atmospheric in situ CH(4) absorption spectra measured in the 1.653-mum region. Mixing ratios are obtained from the absorption spectra by application of a nonlinear least-squares fit to the full molecular line shape in conjunction with in situP and T measurements.     

Sagnac-type fiber-optic array sensor for detection of bulk ultrasonic waves

In this paper, we describe a fiber optic array sensor suitable for detection of bulk ultrasonic waves. This sensor is based on an intrinsic fiber optic Sagnac interferometer. The fiber array is formed by multiple folding of a continuous length of an optical fiber into flat coils. Depending on the orientation of the fiber array with respect to the ultrasonic wave, the proposed sensor can act as a conventional in-phase detector or as a narrowband detector. In the narrowband mode, the center frequency of detection can be tuned by adjusting the spacing of the fiber array elements to be equal to the ultrasonic wavelength of interest. This feature distinguishes this array sensor from conventional hydrophones in which a receiver is typically much smaller than the acoustical wavelength. It is shown that the array sensor provides an enhanced signal-to-noise ratio (SNR) compared with a single element detection scheme. Results are presented for detection of ultrasonic waves in water arising from both piezoelectric and laser ultrasonic sources. Potential areas of application of this sensor include process monitoring, smart structures, bio-medical ultrasound, and chemical sensing.     

Theoretical and experimental studies of Schottky diodes that use aligned arrays of single-walled carbon nanotubes

We present theoretical and experimental studies of Schottky diodes that use aligned arrays of single-walled carbon nanotubes. A simple physical model, taking into account the basic physics of current rectification, can adequately describe the single-tube and array devices. We show that for as-grown array diodes, the rectification ratio, defined by the maximum-to-minimum-current-ratio, is low due to the presence of metallic-single-walled nanotube (SWNT) shunts. These tubes can be eliminated in a single voltage sweep resulting in a high rectification array device. Further analysis also shows that the channel resistance, and not the intrinsic nanotube diode properties, limits the rectification in devices with channel length up to 10 μm.     

Detector efficiency limits on quantum improvement

Abstract

Although the National Institute of Standards and Technology has measured the intrinsic quantum efficiency of Si and InGaAs avalanche photo diode (APD) materials to be above 98% by building an efficient compound detector, commercially available devices have efficiencies ranging between 15 and 75%. This means bandwidth, dark current, cost, and other factors are more important than quantum efficiency for existing applications. For non-classical correlated photon applications, the system's correlated signal-to-noise ratio is proportional to (ηN)^½ /(1 ? η)^½, rather than the classical signal-to-noise (ηN)^½. Consequently, the detector design trade space must be re-evaluated. This paper systematically examines the generic detection process, lays out the considerations needed for designing detectors for non-classical applications, and identifies the ultimate physical limits on quantum efficiency.     

Characterization of a focal plane camera fitted to a Mattauch-Herzog geometry mass spectrograph. 1. Use with a glow-discharge source

A Mattauch-Herzog geometry mass spectrograph (MHMS) has been equipped with a novel array detector, the focal plane camera (FPC). The FPC consists of an array of gold Faraday cups, each coupled to its own integrator, with interrogation of the integrators performed by a multiplexer. The initial coupling of this instrument with a pin-type glow discharge source has provided limits of detection in the single to hundreds of nanograms per gram regime; isotope ratio accuracy and precision better than 5% error and 0.2% RSD, respectively; and a linear dynamic range of at least 6 orders of magnitude. A current weakness of the FPC is its pixel size, which limits both sensitivity and baseline resolution (to R = 130). The minimum data acquisition time for multiple images at present is 1 ms/image, with a dead time of 3.2 ms between images, which will limit the ability of the FPC to monitor extremely short transient signals.     

Attenuated total internal reflectance infrared microspectroscopy as a detection technique for capillary electrophoresis

A novel detector for capillary electrophoresis (CE) using single-bounce attenuated total internal reflectance (ATR) Fourier transform infrared (FT-IR) microspectroscopy is presented. The terminus of the CE capillary is placed approximately 1 microm from the internal reflectance crystal at the focus of an ATR infrared microscope. Using pressure driven flow injection, concentration and volume detection limits have been determined for 25- and 10-microm-i.d. silica capillaries. Upon injection of 820 pL of succinylcholine chloride in a 10-microm capillary, a concentration detection limit of approximately 0.5 parts per thousand (ppt), or 410 pg, is found. The injection volume detection limit using a 108 ppt solution is 2.0 pL (216 pg). Sample separations using a programmed series of pressure, voltage, and again pressure on 25-, 50-, and 75-microm-i.d. capillaries are shown. CE separations of citrate and nitrate, as well as succinylcholine chloride with sodium salicylate using acetone as a neutral marker, are demonstrated. Several advantages of this CE-FT-IR technique include: (1) minimization of postcolumn broadening as a result of a small detector volume; (2) the ability to signal average spectra of the same aliquot, thereby improving the signal-to-noise in a stopped-flow environment; and (3) simplicity of design.     

Effects of dielectric thickness and contact area on current-voltage characteristics of thin film metal-insulator-metal diodes

Planar asymmetric Ni-NiO-Cr/Au thin film Metal-Insulator-Metal (MIM) tunnel diodes were fabricated for use in an ultra-sensitive infrared detector operating at room temperature. MIM diodes with contact areas of 100 μm² and 1 μm² were fabricated using standard Micro-Electro Mechanical Systems techniques. A linear relationship between the thickness of reactively sputtered Nickel Oxide (NiO) and the breakdown voltage was experimentally determined, and the diode performance was verified using a theoretical approach. Current-Voltage measurements of the MIM diode revealed an increase in the current from 1.5 nA to 0.8 mA, when the thickness of the dielectric and the contact area of the detector decreased. Also, the rectification ratios of the detectors were determined, exhibiting an asymmetry of 4.5 at 1 V and 6 at 0.2 V for detectors A and B, respectively. Further, the ratio was observed to be increasing with bias voltage suggesting a strong asymmetric behavior. The results are in agreement with the theoretical predictions confirming conduction via tunneling. The nonlinearity and asymmetry exhibited by these diodes suggests their viability in infrared applications.     

One-dimensional collimation of laser array outputs

We consider a computer-generated hologram for the one-dimensional collimation in x of the output from a linear laser-diode array in y. Our concern is to produce one-dimensional pencil beams from each laser diode with small cross talk between the output from the separate laser diodes. Such outputs can be used in matrix-vector, neural net, and interconnection applications. The efficiency and the design of the computer-generated hologram are detailed, and initial optical laboratory results with an electron-beam recorded computer-generated hologram are presented.     

Instrumentation for medium-throughput two-dimensional capillary electrophoresis with laser-induced fluorescence detection

In two-dimensional capillary electrophoresis, a sample undergoes separation in the first dimension capillary by sieving electrophoresis. Fractions are periodically transferred across an interface into a second dimension capillary, where components are further resolved by micellar electrokinetic capillary electrophoresis. Previous instruments employed one pair of capillaries to analyze a single sample. We now report a multiplexed system that allows separation of five samples in parallel. Samples are injected into five first-dimension capillaries, fractions are transferred across an interface to 5 second-dimension capillaries, and analyte is detected by laser-induced fluorescence in a five-capillary sheath-flow cuvette. The instrument produces detection limits of 940 +/- 350 yoctomoles for 3-(2-furoyl)quinoline-2-carboxaldehyde labeled trypsin inhibitor in one-dimensional separation; detection limits degrade by a factor of 3.8 for two-dimensional separations. Two-dimensional capillary electrophoresis expression fingerprints were obtained from homogenates prepared from a lung cancer (A549) cell line, on the basis of capillary sieving electrophoresis (CSE) and micellar electrophoresis capillary chromatography (MECC). An average of 131 spots is resolved with signal-to-noise greater than 10. A Gaussian surface was fit to a set of 20 spots in each electropherogram. The mean spot width, expressed as standard deviation of the Gaussian function, was 2.3 +/- 0.7 transfers in the CSE dimension and 0.46 +/- 0.25 s in the MECC dimension. The standard deviation in spot position was 1.8 +/- 1.2 transfers in the CSE dimension and 0.88 +/- 0.55 s in the MECC dimension. Spot capacity was 300.     

Frequency Modulation Multiplexing for Simultaneous Detection of Multiple Gases by use of Wavelength Modulation Spectroscopy with Diode Lasers

Modulation frequency multiplexing provides a straightforward method, analogous to television or radio broadcasting, for performing simultaneous detection of multiple gases by use of wavelength modulation spectroscopy with diode lasers. When fiber-optic coupled lasers are used, our approach guarantees that all beams transit the same optical path and impinge on the same detector. Each laser is modulated at a different frequency and the detector output is processed by a set of lock-in amplifiers, one for each laser, to measure the absorbance encountered by each laser.     

Low-Noise Signal Processing Chain for High Capacitance Sensors

A low-noise readout array is proposed for use with high capacitance detectors. The readout array is composed of a preamplifier/amplifier chain. The signal processing chain is designed for use with CdZnTe gamma ray detectors employed by NASA for radiation detection. This approach employs correlated double sampling and capacitive matching to increase the signal-to-noise ratio (SNR). The readout array is custom designed to fit into one detector pixel. The preamplifier/amplifier chain is designed and fabricated in 0.13 $mu$m CMOS8RF IBM technology. The readout array results show that the SNR is significantly improved compared to previous work done in this field.