High-performance, static-coated silicon microfabricated columns for gas chromatography

A procedure is described for the preparation of high-performance etched silicon columns for gas chromatography. Rectangular channels, 150 mum wide by 240 mum deep are fabricated in silicon substrates by gas-phase reactive ion etching. A 0.1-0.2-mum-thick film of dimethyl polysiloxane stationary phase is deposited on the channel walls by filling the channel with a dilute solution in 1:1 n-pentane and dichloromethane and pumping away the solvent. A thermally activated cross-linking agent is used for in situ cross-linking. A 3-m-long microfabricated column generated approximately 12 500 theoretical plates at optimal operating conditions using air as carrier gas. A kinetic model for the efficiency of rectangular cross-section columns is used to evaluate column performance. Results indicate an additional source of gas-phase dispersion beyond longitudinal diffusion and nonequilibrium effects, probably resulting from numerous turns in the gas flow path through the channel. The columns are thermally stable to at least 180 degrees C using air carrier gas. Temperature programming is demonstrated for the boiling point range from n-C5 to n-C12. A 3.0-m-long column heated at 10 degrees C/min obtains a peak capacity of over 100 peaks with a resolution of 1.18 and a separation time of approximately 500 s. With a 0.25-m-long column heated at 30 degrees C/min, a peak capacity of 28 peaks is obtained with a separation time of 150 s. Applications are shown for the analysis of air-phase petroleum hydrocarbons and the high-speed analysis of chemical warfare agent and explosive markers.     

Peak capacity, peak-capacity production rate, and boiling point resolution for temperature-programmed GC with very high programming rates

Recent advances in column heating technology have made possible very fast linear temperature programming for high-speed gas chromatography. A fused-silica capillary column is contained in a tubular metal jacket, which is resistively heated by a precision power supply. With very rapid column heating, the rate of peak-capacity production is significantly enhanced, but the total peak capacity and the boiling-point resolution (minimum boiling-point difference required for the separation of two nonpolar compounds on a nonpolar column) are reduced relative to more conventional heating rates used with convection-oven instruments. As temperature-programming rates increase, elution temperatures also increase with the result that retention may become insignificant prior to elution. This results in inefficient utilization of the down-stream end of the column and causes a loss in the rate of peak-capacity production. The rate of peak-capacity production is increased by the use of shorter columns and higher carrier gas velocities. With high programming rates (100-600 degrees C/min), column lengths of 6-12 m and average linear carrier gas velocities in the 100-150 cm/s range are satisfactory. In this study, the rate of peak-capacity production, the total peak capacity, and the boiling point resolution are determined for C10-C28 n-alkanes using 6-18 m long columns, 50-200 cm/s average carrier gas velocities, and 60-600 degrees C/min programming rates. It was found that with a 6-meter-long, 0.25-mm i.d. column programmed at a rate of 600 degrees C/min, a maximum peak-capacity production rate of 6.1 peaks/s was obtained. A total peak capacity of about 75 peaks was produced in a 37-s long separation spanning a boiling-point range from n-C10 (174 degrees C) to n-C28 (432 degrees C).     

Ultrafast gas chromatographic separation of organophosphor and organosulfur compounds utilizing a microcountercurrent flame photometric detector

A microcountercurrent flame photometric detector (microcc-FPD) was adapted and optimized for ultrafast gas chromatographic (GC) separation and detection of organophosphor (OP) and organosulfur (OS) compounds on short chromatographic columns. Air and hydrogen are introduced to the microcc-FPD from opposite directions, creating a hydrogen-rich flame. In this microcc-FPD, combustion takes place between the burner tips without touching them. The separation between the tips and the flame reduces heat loss from the flame to the surrounding environment, resulting in low hydrogen consumption and a compact flame. The microcc-FPD is capable of detecting very narrow (13 ms) chromatographic peaks. An ultrafast GC separation of a group of six OP and OS compounds is achieved within less than 5 s using fast temperature programming of a 0.5-m-long microbore column. Very fast separations are also demonstrated on a 1-m-long microfabricated column consisting of 150-microm-wide, 240-microm-deep channels, etched in a 1.9-cm square silicon chip, covered with a Pyrex wafer, and statically coated with dimethyl polysiloxane. With a hydrogen flow rate of 10 mL/min, the detection limit for OP is 12 pg of P/s and 3 ng of S/s for OS compounds at a signal-to-noise ratio of 2. The coupling of a microfabricated column and a miniature FPD is an important step toward the development of a miniaturized GC-FPD capable of ultrafast detection of low levels of OP and OS compounds.     

Temperature Programming for High-Speed GC

Fast temperature programming (20-50 °C/min) is used with relatively short separation columns to achieve high-speed separations of mixtures covering a wide boiling point range. A cryofocusing inlet is used to obtain narrow injection plugs. High-speed temperature-programmed chromatograms are evaluated by considering local peak capacity as a function of carbon number and boiling point for the normal alkanes in the range C(8)-C(19). The peak capacity generation rate (peaks per second) as a function of carbon number and the total cumulative peak capacity as a function of time are also considered for various column lengths and carrier gas flow rates. Column lengths in the range 3.6-25.4 m and average carrier gas velocity values in the range 50-200 cm/s are considered. For a 6.8-m-long, 0.25-mm-i.d. column operated at an average carrier gas velocity of about 100 cm/s and using a nominal programming rate of 50 °C/min, C(19) elutes in 178 s with a total peak capacity of 168 peaks. If the programming rate is reduced to 20 °C/min, the C(19) elution time more than doubles but the total peak capacity increases by only 20%. For a 25.4-m-long column using a nominal 50 °C/min programming rate, the C(19) retention time is 262 s with a peak capacity of 279 peaks. The use of average carrier gas flow rates greater than about 100 cm/s, which is common in isothermal high-speed GC, results in a considerable loss in total peak capacity with remarkably little reduction in analysis time.     

Silicon microfabricated column with microfabricated differential mobility spectrometer for GC analysis of volatile organic compounds

A 3.0-m-long, 150-microm-wide, 240-microm-deep channel etched in a 3.2-cm-square silicon chip, covered with a Pyrex wafer, and coated with a dimethyl polysiloxane stationary phase is used for the GC separation of volatile organic compounds. The column, which generates approximately 5500 theoretical plates, is temperature-programmed in a conventional convection oven. The column is connected through a heated transfer line to a microfabricated differential mobility spectrometer. The spectrometer incorporates a 63Ni source for atmospheric-pressure chemical ionization of the analytes. Nitrogen or air transport gas (flow 300 cm(3)/min) drives the analyte ions through the cell. The spectrometer operates with an asymmetric radio frequency (RF) electric field between a pair of electrodes in the detector cell. During each radio frequency cycle, the ion mobility alternates between a high-field and a low-field value (differential mobility). Ions oscillate between the electrodes, and only ions with an appropriate differential mobility reach a pair of biased collectors at the downstream end of the cell. A compensation voltage applied to one of the RF electrodes is scanned to allow ions with different differential mobilities to pass through the cell without being annihilated at the RF electrodes. A unique feature of the device is that both positive and negative ions are detected from a single experiment. The combined microfabricated column and detector is evaluated for the analysis of volatile organic compounds with a variety of functionalities.     

Microfluidic chip to produce temperature jumps for electrophysiology

We developed a microfluidic chip that provides rapid temperature changes and accurate temperature control of the perfusing solution to facilitate patch-clamp studies. The device consists of a fluid channel connected to an accessible reservoir for cell culture and patch-clamp measurements. A thin-film platinum heater was placed in the flow channel to generate rapid temperature change, and the temperature was monitored using a thin-film resistor. We constructed the thermal chip using SU-8 on a glass wafer to minimize the heat loss. The chip is capable of increasing the solution temperature from bath temperature (20 degrees C) to 80 degrees C at an optimum heating rate of 0.5 degrees C/ms. To demonstrate the ability of the thermal chip, we have conducted on-chip patch-clamp recordings of temperature-sensitive ion channels (TRPV1) transfected HEK293 cells. The heat-stimulated currents were observed using whole-cell and cell-attached patch configurations. The results demonstrated that the chip can provide rapid temperature jumps at the resolution of single-ion channels.     

一种硅基集成PCR微芯片的传热数值分析

设计和制作了一种基于MEMS技术的硅基集成PCR（聚合酶链式反应）微芯片,采用有限容积法,边界条件考虑自然对流换热和辐射换热,对PCR微芯片的传热过程进行了数值模拟。主要分析了样品的升、降温速度和样品内部的温度均一性。分析结果表明芯片具有较高的升、降温速度,而且样品内部的温度均一性也满足PCR反应的要求。芯片在温度控制系统下进行了热循环反应,实现了GUS基因的扩增,获得了良好的实验结果。     

Fabrication and testing of bulk micromachined silicon carbide piezoresistive pressure sensors for high temperature applications

This paper explores the development of high-temperature pressure sensors based on polycrystalline and single-crystalline 3C-SiC piezoresistors and fabricated by bulk micromachining the underlying 100-mm diameter (100) silicon substrate. In one embodiment, phosphorus-doped APCVD polycrystalline 3C-SiC (poly-SiC) was used for the piezoresistors and sensor diaphragm, with LPCVD silicon nitride employed to electrically isolate the piezoresistor from the diaphragm. These piezoresistors fabricated from poly-SiC films deposited at different temperatures and doping levels were characterized, showing -2.1 as the best gauge factor and exhibited a sensitivities up to 20.9-mV/V*psi at room temperature. In a second embodiment, epitaxially-grown unintentionally nitrogen-doped single-crystalline 3C-SiC piezoresistors were fabricated on silicon diaphragms, with thermally grown silicon dioxide employed for the piezoresistor electrical isolation from the diaphragm. The associated 3C-SiC/SiO/sub 2//Si substrate was fabricated by bonding a (100) silicon wafer carrying the 3C-SiC onto a silicon wafer with thermal oxide covering its surface. The 3C-SiC handle wafer was then etched away in KOH. The diaphragm was fabricated by time etching the silicon substrate. The sensors were tested at temperatures up to 400/spl deg/C and exhibited a sensitivity of 177.6-mV/V*psi at room temperature and 63.1-mV/V*psi at 400/spl deg/C. The estimated longitudinal gauge factor of 3C-SiC piezoresistors along the [100] direction was estimated at about -18 at room temperature and -7 at 400/spl deg/C.     

Wafer-scale fabrication of polymer-based microdevices via injection molding and photolithographic micropatterning protocols

Because of their broad applications in biomedical analysis, integrated, polymer-based microdevices incorporating micropatterned metallic and insulating layers are significant in contemporary research. In this study, micropatterns for temperature sensing and microelectrode sets for electroanalysis have been implemented on an injection-molded thin polymer membrane by employing conventional semiconductor processing techniques (i.e., standard photolithographic methods). Cyclic olefin copolymer (COC) is chosen as the polymer substrate because of its high chemical and thermal stability. A COC 5-in. wafer (1-mm thickness) is manufactured using an injection molding method, in which polymer membranes (approximately 130 microm thick and 3 mm x 6 mm in area) are implemented simultaneously in order to reduce local thermal mass around micropatterned heaters and temperature sensors. The highly polished surface (approximately 4 nm within 40 microm x 40 microm area) of the fabricated COC wafer as well as its good resistance to typical process chemicals makes it possible to use the standard photolithographic and etching protocols on the COC wafer. Gold micropatterns with a minimum 5-microm line width are fabricated for making microheaters, temperature sensors, and microelectrodes. An insulating layer of aluminum oxide (Al2O3) is prepared at a COC-endurable low temperature (approximately 120 degrees C) by using atomic layer deposition and micropatterning for the electrode contacts. The fabricated microdevice for heating and temperature sensing shows improved performance of thermal isolation, and microelectrodes display good electrochemical performances for electrochemical sensors. Thus, this novel 5-in. wafer-level microfabrication method is a simple and cost-effective protocol to prepare polymer substrate and demonstrates good potential for application to highly integrated and miniaturized biomedical devices.     

Synthesis of gold-silica composite nanowires through solid-liquid-solid phase growth

Nanoscale wires of silicon oxide, and silicon oxide with embedded gold-silicide nanospheres, are synthesized by heating of a gold-coated silicon wafer at temperatures of 1000 degrees C or above, with the resulting wires having diameters ranging from 30 to 150 nm and lengths of approximately 1 mm. This simple fabrication process should make possible economical bulk production of nanowires. Studies indicate that the growth of these gold-silica composite nanowires occurs directly on the silicon wafer by a solid-liquid-solid mechanism.     

静电力驱动的液滴数字传输芯片

设计制作了一种基于静电力驱动的数字微流芯片。通过优化芯片的结构,采用硅为衬底,TiW/Au为微电极阵列,较薄的氮化硅和碳氟聚合物为介质层和疏水膜层,驱动电压大为降低。目前已成功实现了在30V的驱动电压下,对去离子水液滴的两维驱动,液滴移动速度可达96mm/s,同时也实现了对0.9%质量浓度NaCl溶液液滴的驱动。分析结果验证了液滴是在静电力的作用下实现移动。     

Microfluidic platform for liquid chromatography-tandem mass spectrometry analyses of complex peptide mixtures

A microfluidic chip that integrates all the fluidic components of a gradient liquid chromatography (LC) system is described. These chips were batch-fabricated on a silicon wafer using photolithographic processes and with Parylene as the main structural material. The fabricated chip includes three electrolysis-based electrochemical pumps, one for loading the sample and the other two for delivering the solvent gradient; platinum electrodes for delivering current to the pumps and establishing the electrospray potential; a low-volume static mixer; a column packed with silica-based reversed-phase support; integrated frits for bead capture; and an electrospray nozzle. The fabricated structures were able to withstand pressures in excess of 250 psi. The device was used to perform a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of a mixture of peptides from the trypsin digestion of bovine serum albumen (BSA). Gradient elution through the 1.2-cm column was performed at a flow rate of 80 nL/min. Compared to the analysis of the same sample using a commercial nanoflow LC system, the chromatographic resolution was nearly as good, and the total cycle time was significantly reduced because of the minimal volume between the pumps and the column. Results demonstrate the potential of mass-produced, low-cost microfluidic systems capable of performing LC separations for proteomics applications.     

A micromachined poly(vinylidene fluoride-trifluoroethylene)transducer for pulse-echo ultrasound applications

A process for manufacturing epoxy-backed integrated poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] transducers using standard microfabrication techniques is reported. The P(VDF-TrFE) is spin-cast over a silicon membrane, which is backfilled with epoxy to yield a wide-band, half-wavelength (λ/2)-resonant device suitable for pulse-echo use. The main advantages of the fabrication process are the ability to build several devices at a time on a single wafer and the potential for integrating electronics on the same substrate with the transducer. Twelve 31-MHz 2-mm diameter transducers were fabricated on a 2-in diameter silicon wafer. A pulse length of about 100 ns was achieved with a sample device, which exhibited a dynamic range of 40 dB and an insertion loss of 48 dB. The axial resolution of the transducer in healthy vascular tissue was estimated to be 79 μm     

Free-flow electrophoresis on an anodic bonded glass microchip

A micro-free-flow electrophoresis chip has been fabricated into a glass wafer etched with 20-microm-deep channels. Wafers were bonded anodically using an intermediate amorphous silicon film. Electric fields as high as 283 V/cm were applied across the separation channel to obtain baseline resolution of fluorescent standards in 4.8 s. The effect of electric fields ranging from 0 to 283 V/cm on the separations and resulting resolutions were examined. Resolution was shown to increase linearly with the applied electric field. Joule heating was not significant under the conditions tested. Instead, the generation of electrolysis products at higher currents proved to be the limiting factor preventing higher separation potentials from being used.     

转动竖直镜面的微机械光开关

提出并制作了转动竖直微镜的微机械光开关,采用曲线形状的电极设计,有效地减低了悬臂梁驱动器的吸合电压,采用体硅深刻蚀技术结合(110)硅的各向异性腐蚀技术制备了光开关芯片和耦合对准的U形槽和卡簧。芯片经初步封装后进行了电学测试和光学测试,测得吸合电压78.5V,谐振频率2.3kHz,光开关损耗5dB,隔离度45dB。     

Gas chromatography-microchip atmospheric pressure chemical ionization-mass spectrometry

An atmospheric pressure chemical ionization (APCI) microchip is presented for combining a gas chromatograph (GC) to a mass spectrometer (MS). The chip includes capillary insertion channel, stopper, vaporizer channel, nozzle and nebulizer gas inlet fabricated on the silicon wafer, and a platinum heater sputtered on a glass wafer. These two wafers are joined by anodic bonding creating a two-dimensional version of an APCI microchip. The sample from GC is directed via heated transfer line capillary to the vaporizer channel of the APCI chip. The etched nozzle forms narrow sample plume, which is ionized by an external corona discharge needle, and the ions are analyzed by a mass spectrometer. The GC-microchip APCI-MS combination provides an efficient method for qualitative and quantitative analysis. The spectra produced by microchip APCI show intensive protonated molecule and some fragmentation products as in classical chemical ionization for structure elucidation. In quantitative analysis the GC-microchip APCI-MS showed good linearity (r(2) = 0.9989) and repeatability (relative standard deviation 4.4%). The limits of detection with signal-to-noise ratio of three were between 0.5 and 2 micromol/L with MS mode using selected ion monitoring and 0.05 micromol/L with MS/MS using multiple reaction monitoring.     

大面积高深宽比微结构硅片的热氧化实验研究

利用大面积硅片制作X射线光栅和硅基微通道板等都涉及硅的热氧化工艺。热氧化使具有高深宽比微结构的大面积硅片产生形变,严重影响了这些器件的应用。本文以5英寸硅片为例,研究了硅基微结构在热氧化过程中的变形问题,定性分析了产生形变的力学因素,提出了减小形变的氧化方法。首先实验制作了具有高深宽比微结构的硅片,采用不同的氧化方法,比较了变形的大小。结果表明,通过控制热氧化过程中的温度来控制热膨胀系数和在热氧化过程中施加外部热塑应力等方法能够有效地减小热氧化变形量。     

General strategy for performing temperature programming in high performance liquid chromatography: prediction of linear temperature gradients

This paper describes how an empirical retention model is transferred from temperature-programmed gas chromatography (GC) to high temperature liquid chromatography (HT-HPLC). In order to evaluate the retention prediction, a temperature range from 50 to 180 °C was investigated using two test mixtures consisting of steroids and polycyclic aromatic hydrocarbons. In this temperature range, heating rates from 1.5 °C min(-1) up to 30 °C min(-1) were applied using four different high temperature stable HPLC columns with inner diameters of 1.0, 2.1, 3.0, and 4.6 mm. Temperature lag phenomena in the HPLC column as well as in the column oven are discussed, and it is shown that the linear elution strength (LES) model can be applied without any mathematical extension in order to take a temperature-dependent delay time into account. On the basis of this approximation, it is possible to perform a systematic method development using linear temperature gradients in liquid chromatography. Furthermore, it is shown that only two initial temperature gradient runs are necessary to predict the retention times of the analytes with a maximal relative error of less than 2%.     

Capacitorless 1T-DRAM on crystallized poly-Si TFT

The single-transistor dynamic random-access memory (1T-DRAM) using a polycrystalline-silicon thin-film transistor (poly-Si TFT) was investigated. A 100-nm amorphous silicon thin film was deposited onto a 200-nm oxidized silicon wafer via low-pressure chemical vapor deposition (LPCVD), and the amorphous silicon layer was crystallized via eximer laser annealing (ELA) with a KrF source of 248 nm wavelength and 400 mJ/cm2 power. The fabricated capacitor less 1T-DRAM on the poly-Si TFT was evaluated via impact ionization and gate-induced drain leakage (GIDL) current programming. The device showed a clear memory margin between the "1" and "0" states, and as the channel length decreased, a floating body effect which induces a kink effect increases with high mobility. Furthermore, the GIDL current programming showed improved memory properties compared to the impact ionization method. Although the sensing margins and retention times in both program methods are commercially insufficient, it was confirmed the feasibility of the application of 1T-DRAM operation to TFTs.     

Requirements for laser-induced desorption/ionization on submicrometer structures

Laser-induced and matrix-free desorption/ionization on various submicrometer structures was investigated. First, to examine the effect of surface roughness on ionization, a silicon wafer or stainless steel was scratched with sandpaper. The fluences of a 337-nm nitrogen laser, required for ionization of synthetic polymers and reserpine, were markedly reduced on the scratched stainless steel or silicon as compared to the corresponding untreated surface. Next, arrays of submicrometer grooves, which had been lithographically fabricated on a silicon wafer, yielded protonated angiotensin, and the morphologic orientation demonstrated the positive relation between the laser and groove directions for promoting ionization. The fabricated structure also suggested the submicrometer, but not smaller, or nanometer, structures to be a key factor in direct desorption/ionization on rough surfaces. Finally, submicrometer porous structures of alumina or polyethylene yielded intense molecular ion signals of angiotensin and insulin, in response to direct UV irradiation, when the surface was coated with Au or Pt. The coating provided the additional advantage of prolonged activity for a porous alumina chip, exceeding a month even when the chip was left in the open air. These results indicate that laser-induced desorption/ionization of organic compounds can be implemented on submicrometer structures with an Au- or Pt-coated surface irrespective of the basal materials.