Nanoelectronic interface for lab-on-a-chip devices

Innovations in microfabricated analytical devices integrated with microelectronic circuits and biological cells show promising results in detection, diagnosis and analysis. Planar metallic microelectrodes are widely used for the electrical interface with the biological cells. Issues with the current microelectrode array design are the difficulty in selective integration with a cell, the size dependency of its impedance and the large amount of noise in the circuit due to this mismatch. It is quite evident that an approach utilizing nanotechnology can solve some of these problems by yielding efficient electrical interconnections. The design and development of a planar microelectrode array integrated with vertically aligned nanowires for lab-on-achip (LoC) device applications are presented. The nanowire integrated microelectrode arrays for LoC devices show promising results with respect to impedance control due to increased surface area. The authors have fabricated nanowire integrated microelectrode arrays on silicon and flexible polymer substrates using the template method. A high degree of specific growth is achieved by controlling the nanowire synthesis parameters. An attempt has been made to integrate biological cells into the nanowires by culturing endothelial cells onto the microelectrode array.     

A lab-on-a-chip for cell detection and manipulation

Presents a lab-on-a-chip for electronic manipulation and detection of microorganisms based on the use of closed dielectrophoretic (DEP) cages combined with impedance sensing. A printed circuit board (PCB) prototype has been used to trap, concentrate, and quantify polystyrene micro-beads in agreement with CAD simulations. The experiment was successfully repeated with S. cerevisiae. The results prove the effectiveness of the approach for particle manipulation and detection without the need for external optical components nor chemical labeling. With the proposed approach, particle concentration may be increased on-chip of more than three orders of magnitude, correspondingly boosting the detection sensitivity.     

Review: carbon nanotube for microfluidic lab-on-a-chip application

Microfluidic lab-on-a-chip allows chemical and biochemical analysis to be conducted in a miniaturized system. Miniaturized analysis reduces the reagent consumption while decreasing the overall size of the device, but the small dose of the sample make detection more demanding and is more sensitive to adsorption of species on the surface. Integration of carbon nanotubes into microfludic devices is a promising approach. This review addresses recent advances in the application of carbon nanotubes for microfluidic lab-on-a-chip. The literature review shows that carbon nanotubes have been used to achieve superlubrifying microchannels, act as high density nanoporous membranes, electrical transducers mainly in flow sensors and biosensors, and mimics of living systems. In addition, extensive work has been carried out to investigate the tunable mechanical, chemical and electrical properties of carbon nanotubes in order to manipulate and analyse extremely small volumes of fluid effectively.     

Multiscale variation-aware techniques for high-performance digital microfluidic lab-on-a-chip component placement

The invention of microfluidic lab-on-a-chip alleviates the burden of traditional biochemical laboratory procedures which are often very expensive. Device miniaturization and increasing design complexity have mandated a shift in digital microfluidic lab-on-a-chip design from traditional manual design to computer-aided design (CAD) methodologies. As an important procedure in the lab-on-a-chip layout CAD, the lab-on-a-chip component placement determines the physical location and the starting time of each operation such that the overall completion time is minimized while satisfying nonoverlapping constraint, resource constraint, and scheduling constraint. In this paper, a multiscale variation-aware optimization technique based on integer linear programming is proposed for the lab-on-a-chip component placement. The simulation results demonstrate that without considering variations, our technique always satisfies the design constraints and largely outperforms the state-of-the-art approach, with up to 65.9% reduction in completion time. When considering variations, the variation-unaware design has the average yield of 2%, while our variation-aware technique always satisfies the yield constraint with only 7.7% completion time increase.     

An integrated fluorescence array as a platform for lab-on-a-chip technology using multimode interference splitters

We present the design and fabrication of 1-to-N multimode interference (MMI) splitters, suitable for use in integrated optical fluorescence array sensing, with particular applications in lab-on-a-chip (micro-TAS) technologies. Electron beam irradiation of germanium-doped flame hydrolysis deposited silica was used to define the MMI waveguide regions. The splitters were integrated with microfluidic channels to form direct-excitation fluorescence sensor chips for use at visible wavelengths. Characterization of the waveguides shows that predictable splitting ratios can be achieved. Two devices are presented: a 1/spl times/2 splitter integrated with one analytical chamber and a 1/spl times/4 array device for multipoint excitation. A photomultiplier tube was used to assess the analytical performance of the chip, in response to standard aliquots of fluorophore (31 nM to 1.25 /spl mu/M).     

Carbon nanotubes for voltage reduction and throughput enhancement of electrical cell lysis on a lab-on-a-chip

We report on the enhancement of electrical cell lysis using carbon nanotubes (CNTs). Electrical cell lysis systems are widely utilized in microchips as they are well suited to integration into lab-on-a-chip devices. However, cell lysis based on electrical mechanisms has high voltage requirements. Here, we demonstrate that by incorporating CNTs into microfluidic electrolysis systems, the required voltage for lysis is reduced by half and the lysis throughput at low voltages is improved by ten times, compared to non-CNT microchips. In our experiment, E. coli cells are lysed while passing through an electric field in a microchannel. Based on the lightning rod effect, the electric field strengthened at the tip of the CNTs enhances cell lysis at lower voltage and higher throughput. This approach enables easy integration of cell lysis with other on-chip high-throughput sample-preparation processes.     

Toward integrated detection and graphene-based removal of contaminants in a lab-on-a-chip platform

A novel miniaturized microfluidic platform was developed for the simultaneous detection and removal of polybrominated diphenyl ethers (PBDEs).The platform consists of a polydimethylsiloxane (PDMS) microfluidic chip for an immunoreaction step,a PDMS chip with an integrated screen-printed electrode (SPCE) for detection,and a PDMS-reduced graphene oxide (rGO) chip for physical adsorption and subsequent removal of PBDE residues.The detection was based on competitive immunoassay-linked binding between PBDE and PBDE modified with horseradish peroxidase (HRP-PBDE) followed by the monitoring of enzymatic oxidation of o-aminophenol (o-AP) using square wave anodic stripping voltammetry (SW-ASV).PBDE was detected with good sensitivity and a limit of detection similar to that obtained with a commercial colorimetric test (0.018 ppb),but with the advantage of using lower reagent volumes and a reduced analysis time.The use of microfluidic chips also provides improved linearity and a better reproducibility in comparison to those obtained with batch-based measurements using screen-printed electrodes.In order to design a detection system suitable for toxic compounds such as PBDEs,a reduced graphene oxide-PDMS composite was developed and optimized to obtain increased adsorption (based on both the hydrophobicity and π-π stacking between rGO and PBDE molecules) compared to those of non-modified PDMS.To the best of our knowledge,this is the first demonstration of electrochemical detection of flame retardants and a novel application of the rGO-PDMS composite in a biosensing system.This system can be easily applied to detect any analyte using the appropriate immunoassay and it supports operation in complex matrices such as seawater.     

Bead-based DNA diagnostic assay for chlamydia using nanoparticle-mediated surface-enhanced resonance Raman scattering detection within a lab-on-a-chip format

There is a continued interest in the development of new on-chip protocols for the determination of the causes of infectious disease. In this paper, we demonstrate the use of surface-enhanced resonance Raman scattering (SERRS) for detecting the clinically relevant nucleic acid sequences of Chlamydia trachomatis in a bead-based lab-on-a-chip format, incorporating a solid-phase sample clean-up on-chip. The assay uses streptavidinated polymer microspheres to capture a biotinylated PCR product of the oligonucleotide sequence, which was subsequently hybridized against a complementary rhodamine-labeled, Raman active probe. Central to the assay is an in-channel integrated microfilter, which was used to retain the microspheres, enabling the bound target to be separated from the rest of the sample as part of a solid-phase clean-up (thereby removing any contributions from the background). After washing, the bound Rhodamine labeled detection probe was released thermally from the microspheres by heating and was subsequently mixed on-chip with a stream of silver nanoparticles. The signal was detected downstream using a Raman spectrometer to collect the SERRS response. The assay offers several advantages over traditional laboratory methods, including: the speed of the assay on-chip, the potential for sample clean-up; and the low volume of sample required.     

Online-calibration for reliable and robust lab-on-a-chip surface enhanced Raman spectroscopy measurement in a liquid/liquid segmented flow

Concerning the usability of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS) for analytical tasks applying chemometric data evalutation, a secure, reproducible, and stable data output independent of inconsistent ambient conditions has to be accomplished. In this contribution, we present a new approach to achieve reliable and robust measurements based on segmented flow LOC-SERS via online-wavenumber calibration.     

Polyaniline-carboxymethyl cellulose nanocomposite for cholesterol detection

Cholesterol oxidase (ChOx) has been covalently immobilized onto polyaniline-carboxymethyl cellulose (PANI-CMC) nanocomposite film deposited onto indium-tin-oxide (ITO) coated glass plate using glutaraldehyde as a cross-linker. Fourier transform infrared (FTIR) spectroscopic and electrochemical studies have been used to characterize the PANI-CMC/ITO nanocomposite electrode and ChOx/PANI-CMC/ITO bioelectrode. Scanning electron microscopy (SEM) studies reveal the formation of PANI-CMC nanocomposite fibers of size approximately 150 nm in diameter. The ChOx/PANI-CMC/ITO bioelectrode exhibits linearity as 0.5-22 mM, detection limit as 1.31 mM, sensitivity as 0.14 mA/mM cm2, response time as 10 s and shelf-life of about 10 weeks when bioelectrode is stored at 4 degrees C. The low value of Michaelis-Menten constant (K(m)) obtained as 2.71 mM reveals high affinity of immobilized ChOx for PANI-CMC/ITO nanocomposite electrode.     

Verilog HDL数字电路的设计

Verilog HDL(硬件描述语言)是目前世界上使用最广泛的符合—IEEE标准的硬件描述语言之一，在数字系统设计的仿真和综合领域中有着强大的发展潜力。本文介绍了硬件描述语言verilog HDL的特点和使用方法，并通过一个实例——自动售饮料机的程序的应用，展现了Verilog HDL在数字电路设计上的优越性。     

Spectrometric determination of the refractive index of optical wave guiding materials used in lab-on-a-chip applications

The design and optimization of light-based analytical devices often require optical characterization of materials involved in their construction. With the aim of benefiting lab-on-a-chip applications, a transmission spectrometric method for determining refractive indices, n, of transparent solids is presented here. Angular dependence of the reflection coefficient between material-air interfaces constitutes the basis of the procedure. Firstly, the method is studied via simulation, using a theoretical algorithm that describes the light propagation through the sample slide, to assess the potentially attainable accuracy. Simulations also serve to specify the angles at which measurements should be taken. Secondly, a visible light source and an optical fiber spectrometer are used to perform measurements on three commonly used materials in optical lab-on-a-chip devices. A nonlinear regression subroutine fits experimental data to the proposed theoretical model and is used to obtain n. Because the attainable precision using this method of refractive index determination is dictated by the uncertainty in the transmission measurements, the precision (with 95% confidence) for mechanically rigid samples, namely glass and poly(methyl methacrylate) (PMMA), is higher than those estimated for the elastomer sample (in-house-molded poly(dimethylsiloxane) (PDMS)). At wavelengths with the highest signal-to-noise ratio for the spectrometer setup, the estimated refractive indices were 1.43+/-0.05 (580 nm) for PDMS, 1.54+/-0.02 (546 nm) for glass, and 1.485+/-0.005 (656 nm) for PMMA. Accurate refractive index estimations with an average precision equal to 0.01 refractive index units (RIU) were obtained for PMMA and glass samples, and an average precision of 0.09 RIU for the PDMS molded slide between 550 and 750 nm was obtained.     

自旋电子学功能材料

巨磁电阻效应的发现开拓了磁电子学的新领域,20世纪90年代,磁电子学得到迅速的发展,并在应用上取得显著的经济效益与巨大的社会效应,本世纪初,研究的重点已转移到半导体自旋电子学的新方向,并已取得重要的进展.本文将结合我们科研组的研究工作,概述从磁电子学到半导体自旋电子学材料的发展,重点介绍稀磁半导体材料研究的进展.     

Effects of ethanol volume percent on fluorescein-labeled spinach apo- and holocalmodulin

We report the effects of EtOH volume percent (0-70%) on spinach apo- and holocalmodulin that have been site-selectively labeled with fluorescein (F). In these experiments, calmodulin (CaM) has one F reporter group attached to Cys-26, and this site is located immediately adjacent to one of the four primary Ca(2+)-binding sites (EF hands). The optimum analytical CaM-F sensitivity to Ca2+ occurs between approximately 10 and 30% EtOH. Our results also show that added EtOH causes changes in CaM and these changes are surprisingly different for apo- and holo-CaM. Apo-CaM-F appears to lose one of its two waters of hydration at approximately 20% EtOH and retains one water of hydration between approximately 20 and 70% EtOH. In apo-CaM-F, the semiangle that describes the range over which the fluorescein reporter group can precess remains essentially constant (42 +/- 2 degrees) between 0 and 70% EtOH. This shows that the fluorescein reporter group precessional freedom in apo-CaM-F is not affected significantly by EtOH. Holo-CaM-F also appears to lose one water of hydration at approximately 20-30% EtOH but then appears to denature as the EtOH volume percent increases. The fluorescein reporter group semiangle within holo-CaM-F decreases from 43 +/- 1 degrees in neat aqueous buffer to 36 +/- 1 degrees at 70% EtOH. This shows that holo-CaM-F is less nativelike and the EF hand "closes down" about the fluorescein reporter group in holo-CaM-F as the EtOH volume percent increases.     

Functional microfabricated sample targets for matrix-assisted laser desorption/ionization mass spectrometry analysis of ribonucleic acids

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful analytical tool for the structural characterization of proteins and nucleic acids. However, many proteomics or genomics methodologies that employ MALDI-MS require external sample manipulation, which limits the overall throughput of analysis. We have focused on fabricating functional MALDI sample plates that would permit the on-probe characterization of nucleic acids. Here, we present results arising from the fabrication of functional sample plates composed of poly(methyl methacrylate) (PMMA). The PMMA sample plates were fabricated by a CNC milling technique. The key structural feature of our microfabricated samples plates is the presence of individual cylindrical posts (360 microm x 360 microm), which serve as individual sample targets within the overall PMMA-based MALDI sample plate. Functionality is added to these microposts via the covalent attachment of enzymes. As an example of the applicability of these microfabricated sample plates, enzymatic digestion of ribonucleic acids was performed on probe (i.e., on the micropost) with subsequent analysis by MALDI-MS. Advantages to such an approach include a reduction in sample handling (and concomitant sample losses) and a reduction in the amount of sample required for analysis due to the small surface area of the microposts.     

Calculating monitoring reliability parameters on the basis of the percent rejection

Translated from Izmeritel'naya Tekhnika, No. 8, pp. 16–18, August, 1989.