膜法提取甘露醇过程中膜的微生物污染及其控制

报告了海藻工业膜集成技术提取甘露醇工业化生产过程中膜的微生物污染及其控制的研究结果和长期运行的措施、经验．研究和运行结果表明，膜法提取甘露醇过程，极易发生微生物污染，且发展迅猛，危害严重．影响微生物污染的因素比较复杂，其主要因素是料液水温、含盐浓度、系统设计和运行状况；与常规膜法水处理过程不同，控制发生微生物污染，除了监控进料液SDI指标外，还要求控制进料液内菌群总数小于或等于2000cfv／mL；需重视清洗和杀菌消毒系统设计，确保清洗、杀菌剂能充满一切管阀、部件空间并清洗到每一个部分；选用尽量简短的工艺流程和抗污染膜组件；采用经济、有效、安全的杀菌剂并按规范程序进行消毒，只要严格按上述措施操作就可控制其微生物污染，保障系统稳妥运行．     

Three-layer flow membrane system on a microchip for investigation of molecular transport

A stable three-layer flow system, water/organic solvent/water, has been successfully applied for the first time in a microchannel to get rapid transport through an organic liquid membrane. In the continuous laminar flow region, the analyte (methyl red) was rapidly extracted across the microchannel from the donor to the acceptor phase through the organic solvent phase (cyclohexane). Thermal lens microscopy was used to monitor the process. The thickness of the organic phase, sandwiched by the two aqueous phases, was approximately 64 microm, and it was considered as a thin liquid organic membrane. Permeability studies showed the effects of molecular diffusion, layer thickness, and organic solvent-water partition coefficient on the molecular transport. In the microchip, complete equilibration was achieved in several seconds, in contrast to a conventionally used apparatus, where it takes tens of minutes. The thickness of the organic and aqueous boundary layers was defined as equal to the microchannel dimensions, and the organic solvent-water partition coefficient was determined on a microchip using the liquid/liquid extraction system. Experimental data on molecular transport across the organic membrane were in agreement with the calculated permeability based on the three-compartment water/organic solvent/water model. This kind of experiment can be performed only in a microspace, and the system can be considered as a potential biological membrane for future in vitro study of drug transport.     

A fully integrated monolithic microchip electrospray device for mass spectrometry

A novel microfabricated nozzle has been developed for the electrospray of liquids from microfluidic devices for analysis by mass spectrometry. The electrospray device was fabricated from a monolithic silicon substrate using deep reactive ion etching and other standard semiconductor techniques to etch nozzles from the planar surface of a silicon wafer. A channel extends through the wafer from the tip of the nozzle to a reservoir etched into the opposite planar surface of the wafer. Nozzle diameters as small as 15 microm have been fabricated using this method. The microfabricated electrospray device provides a reproducible, controllable, and robust means of producing nano-electrospray of a liquid sample. The electrospray device was interfaced to an atmospheric pressure ionization time-of-flight mass spectrometer using continuous infusion of test compounds at low nanoliter-per-minute flow rates. Nozzle-to-nozzle signal intensity reproducibility using 10 nozzles was demonstrated to be 12% with single-nozzle signal stability routinely less than 4% relative standard deviation (RSD). Solvent compositions have been electrosprayed ranging from 100% organic to 100% aqueous. The signal-to-noise ratio from the infusion of a 10 nM cytochrome c solution in 100% water at 100 nL/min was 450:1. Microchip electrospray nozzles were compared with pulled capillaries for overall sensitivity and signal stability for small and large molecules. The microchip electrospray nozzles showed a 1.5-3-times increase in sensitivity compared with that from a pulled capillary, and signal stability with the microchip was 2-4% RSD compared with 4-10% with a pulled capillary. Electrospray device lifetimes achieved thus far have exceeded 8 h of continuous operation and should be sufficient for typical microfluidic applications. The total volume of the electrospray device is less than 25 pL, making it suitable for combination with microfluidic separation devices.     

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。     

Continuous-flow chemical processing on a microchip by combining microunit operations and a multiphase flow network

A new design and construction methodology for integration of complicated chemical processing on a microchip was proposed. This methodology, continuous-flow chemical processing (CFCP), is based on a combination of microunit operations (MUOs) and a multiphase flow network. Chemical operations in microchannels, such as mixing, reaction, and extraction, were classified into several MUOs. The complete procedure for Co(II) wet analysis, including a chelating reaction, solvent extraction, and purification was decomposed into MUOs and reconstructed as CFCP on a microchip. Chemical reaction and molecular transport were realized in and between continuous liquid flows in a multiphase flow network, such as aqueous/aqueous, aqueous/organic, and aqueous/organic/aqueous flows. When the determination of Co(II) in an admixture of Cu(II) was carried out using this methodology, the determination limit (2sigma) was obtained as 18 nM, and the absolute amount of Co chelates detected was 0.13 zmol, that is, 78 chelates. The sample analysis time was faster than that of a conventional processing system. Moreover, troublesome operations such as phase separation and acid and alkali washing, all necessary for the conventional system, were simplified. The CFCP methodology proposed here can be applied to various on-chip applications.     

Photothermal temperature control of a chemical reaction on a microchip using an infrared diode laser

We have demonstrated that a miniaturized device with IR laser heating of the solvent, based on a photothermal effect, is capable of fast and localized control of an enzymatic reaction on a microchip under flow conditions. Using noncontact spectroscopic temperature-sensing techniques, we measured temperature dynamics and spatial distribution and compared the measurements with results of numerical simulation analysis. The device was operated at ultrafast heating and cooling rates of 67 and 53 degrees C/s, respectively, which is 30 times faster than conventional systems and 3-6 times faster than electrothermal miniaturized thermocyclers. The IR laser-mediated heater is characterized by a significantly reduced heated volume of only 5 nL, compared to existing chip-based systems with electrothermal heating. Direct heating of a sample with extremely small heat capacity led us to a fast heating rate, and efficient heat removal through heat transfer to the glass substrate resulted in a fast cooling rate. Reproducible temperature levels with dwell times shorter than 0.5 s were achieved. The enzyme reaction on a chip was successfully controlled with 0.6-s time resolution, using periodic photothermal heating by IR laser. The IR diode laser is compact and thus suits well the miniaturized system design. Our work gives the basis for integration in a chip format of a variety of chemical processes that require fast temperature control.     

Capillary-assembled microchip for universal integration of various chemical functions onto a single microfluidic device

A novel concept for assembling various chemical functions onto a single microfluidic device is proposed. The concept, called a capillary-assembled microchip, involves embedding chemically functionalized capillaries into a lattice microchannel network fabricated on poly(dimethylsiloxane) (PDMS). The network has the same channel dimensions as the outer dimensions of the capillaries. In this paper, we focus on square capillaries to be embedded into a PDMS microchannel network having a square cross section. The combination of hard glass square capillary and soft square PDMS channel allows successful fabrication of a microfluidic device without any solution leakage, and which can use diffusion-based two-solution mixing. Two different types of chemically modified capillaries, an ion-sensing capillary and a pH-sensing capillary, are prepared by coating a hydrophobic plasticized poly(vinyl chloride) membrane and a hydrophilic poly(ethyleneglycol) membrane containing functional molecules onto the inner surface of capillaries. Then, they are cut into appropriate lengths and arranged on a single microchip to prepare a dual-analyte sensing system. The concept proposed here offers advantages inherent to using a planar microfluidic device and of chemical functionality of immobilized molecules. Therefore, we expect to fabricate various types of chemically functionalized microfluidic devices soon.     

Three-electrode electrochemical detector and platinum film decoupler integrated with a capillary electrophoresis microchip for amperometric detection

This article demonstrates that a three-electrode electrochemical (EC) detector and an electric decoupler could be fabricated in the same glass chip and integrated with an O2-plasma-treated PDMS layer using microfabrication techniques to form the capillary electrophoresis (CE) microchip. The platinized decoupler could mostly decouple the electrochemical detection circuit from the interference of an separation electric field in 10 mM 2-(N-morpholino)ethanesulfonic acid (MES, pH 6.5) solution. The baseline offset of background current recorded from the working electrode with and without application of a separation electric field was maintained at less than 0.05 pA in 10 mM MES. In addition, the platinized pseudoreference electrode was demonstrated to offer a stable potential in electrochemical detection. As a consequence, the limit of detection of dopamine was 0.125 microM at a S/N = 4. The responses for dopamine to different concentrations were found to be linear between 0.25 and 50 microM with a correlation coefficient of 0.9974 and a sensitivity of 11.76 pA/microM. The totally integrated CE-EC microchip should be able to fulfill the ideal of miniaturization and commercialization.     

Water as a reaction medium for clean chemical processes

Solvent usage is often an integral part of manufacturing process, whether it is chemical or another industrial sector. Thus, this unavoidable choice of a specific solvent for a desired manufacturing process can have profound economical, environmental, and societal implications. Some of the impacts are long lasting especially from an environmental perspective, which has been well documented in the scientific literature. The pressing need to develop alternative solvents for manufacturing processes originates, in part, from these implications and constitutes an essential strategy under an emerging field of green chemistry. Whereas there have been excellent advances in developing several alternative clean solvents, it is unlikely that the one solvent will be a panacea for various chemical protocols. This article provides some examples of using water as an alternative solvent for chemical reactions with wide-ranging possibilities that include direct use of water soluble renewable materials, C–C bond forming reactions using organometallic reagents, and exploiting the use of alternate energy sources such as solar, microwave and ultrasound in accelerating chemical syntheses.An erratum to this article can be found at     

Water as a reaction medium for clean chemical processes

Solvent usage is often an integral part of manufacturing process, whether it is chemical or another industrial sector. Thus, this unavoidable choice of a specific solvent for a desired manufacturing process can have profound economical, environmental, and societal implications. Some of the impacts are long lasting especially from an environmental perspective, which has been well documented in the scientific literature. The pressing need to develop alternative solvents for manufacturing processes originates, in part, from these implications and constitutes an essential strategy under an emerging field of green chemistry. Whereas there have been excellent advances in developing several alternative clean solvents, it is unlikely that the one solvent will be a panacea for various chemical protocols. This article provides some examples of using water as an alternative solvent for chemical reactions with wide-ranging possibilities that include direct use of water soluble renewable materials, C–C bond forming reactions using organometallic reagents, and exploiting the use of alternate energy sources such as solar, microwave and ultrasound in accelerating chemical syntheses.The online version of the original article can be found at     

Protein sizing on a microchip

We have developed a microfabricated analytical device on a glass chip that performs a protein sizing assay, by integrating the required separation, staining, virtual destaining, and detection steps. To obtain a universal noncovalent fluorescent labeling method, we have combined on-chip dye staining with a novel electrophoretic dilution step. Denatured protein-sodium dodecyl sulfate (SDS) complexes are loaded on a chip and bind a fluorescent dye as the separation begins. At the end of the separation channel, an intersection is used to dilute the SDS below its critical micelle concentration before the detection point. This strongly reduces the background due to dye molecules bound to SDS micelles and also increases the peak amplitude by 1 order of magnitude. Both the on-chip staining and SDS dilution steps occur in the 100-ms time scale and are approximately 10(4) times faster than their conventional counterparts in SDS-PAGE. This represents a much greater speed increase due to microfabrication than has been obtained in other assay steps such as electrophoretic separations. We have designed and tested a microchip capable of sequentially analyzing 11 different samples, with sizing accuracy better than 5% and high sensitivity (30 nM for carbonic anhydrase).     

Determination of carcinoembryonic antigen in human sera by integrated bead-bed immunoassay in a microchip for cancer diagnosis

A bead-bed immunoassay system was structured on a microchip and applied to determine carcinoembryonic antigen (CEA), which is a commonly used marker of colon cancer. Polystyrene beads precoated with anti-CEA antibody were introduced into a microchannel, and then a serum sample containing CEA, the first antibody, and the second antibody conjugated with colloidal gold were reacted successively. The resulting antigen-antibodies complex, fixed on the bead surface, was detected using a thermal lens microscope (TLM). A highly selective and sensitive determination of an ultratrace amount of CEA in human sera was made possible by a sandwich immunoassay system that needs three antibodies for an assay. A detection limit dozens of times lower than the conventional ELISA was achieved. Moreover, when serum samples for 13 patients were assayed with this system, there was a high correlation (r = 0.917) with the conventional ELISA. The integration reduced the time necessary for the antigen-antibody reaction to approximately 1%, thus shortening the overall analysis time from 45 h to 35 min. Moreover, troublesome operations required for conventional heterogeneous immunoassays could be much simplified. This microchip-based diagnosis system is the first microchip-based system that is practically useful for clinical diagnoses with short analysis time, high sensitivity, and easy procedures.     

Integrated sustainability assessment for chemical processes

Policies on sustainable development have resulted in the wide concern about economic, safety, and environmental-friendly chemical production. This work focuses on the development of a holistic methodology that enables the evaluation and comparison of process sustainability in an integrated system. This methodology is proposed based on material and energy flows, process parameters, and process configuration. It uses a set of criteria, including inherent safety, potential environmental impact, and economic aspects. These criteria as the basis for determining the integrated index can be used to perform sustainability assessment for process alternatives under investigation. The multi-criteria decision analysis procedure is presented to conduct the integrated assessment based on qualitative and quantitative analysis. As a case study, ethanol production process, i.e., ethylene-derived feedstock process (A1) and straw cellulose-derived feedstock process (A2) are used to illustrate the proposed methodology. Results showed that A1 had advantage over A2 for the economic aspect while A2 had better performance in the environmental and safety aspects. A2 is the prior option from the point of view of comprehensive evaluation.     

Electrochemistry-based real-time PCR on a microchip

The development of handheld instruments for point-of-care DNA analysis can potentially contribute to the medical diagnostics and environmental monitoring for decentralized applications. In this work, we demonstrate the implementation of a recently developed electrochemical real-time polymerase chain reaction (ERT-PCR) technique on a silicon-glass microchip for simultaneous DNA amplification and detection. This on-chip ERT-PCR process requires the extension of an oligonucleotide in both solution and at solid phases and intermittent electrochemical signal measurement in the presence of all the PCR reagents. Several important parameters, related to the surface passivation and electrochemical scanning of working electrodes, were investigated. It was found that the ERT-PCR's onset thermal cycle ( approximately 3-5), where the analytical signal begins to be distinguishable from the background, is much lower than that of the fluorescence-based counterparts for high template DNA situations (3 x 10(6) copies/microL). By carefully controlling the concentrations of the immobilized probe and the enzyme polymerase, improvements have been made in obtaining a meaningful electrochemical signal using a lower initial template concentration. This ERT-PCR technique on a microchip platform holds significant promise for rapid DNA detection for point-of-care testing applications.     

Bead-assisted displacement immunoassay for staphylococcal enterotoxin B on a microchip

A microchip-based, displacement immunoassay for the sensitive laser-induced fluorescence detection of staphylococcal enterotoxin B is presented. The glass microchip device consists of a microchannel that contains a double weir structure for supporting antibody-functionalized microbeads. After a 30-min sample preparation step, the displacement assay was performed without user intervention and produced quantitative results in an additional 20 min. Linear detection responses were observed over 6 orders of magnitude and provided detection limits down to 1 fM (28.5 fg/mL). The surprisingly low detection limits are hypothesized to arise from field-based enrichment analogous to field-amplified stacking, chromatographic effects, and limited diffusion lengths in the microbead bed. The assay was challenged with bovine serum albumin, casein, and milk sample matrixes. This system has the potential to provide highly sensitive detection capabilities for target biomolecules.     

Electroosmotic flow-based pump for liquid chromatography on a planar microchip

An electroosmotic flow (EOF)-based pump, integrated with a sol-gel stationary phase located in the electric field-free region of a microchip, enabled the separation of six nitroaromatic and nitramine explosives and their degradation products via liquid chromatography (LC). The integrated pump and LC system were fabricated within a single quartz substrate. The pump region consisted of a straight channel (3.0 cm x 230 microm x 100 microm) packed with 5-microm porous silica beads. The sol-gel stationary phase was derived from a precursor mixture of methyltrimethoxy- and phenethyltrimethoxysilanes and was synthesized in the downstream, field-free region of the microchip, resulting in a stationary-phase monolith with dimensions of 2.6 cm x 230 microm x 100 microm. Fluid dynamic design considerations are discussed, especially as they relate to integrating the EOF pump with the LC system. Pump and separation performance, as characterized by flow rate measurements, injection, elution, separation, and detection, point to a viable analytical chemistry platform that encompasses all of the benefits expected of portable, laboratory-on-chip systems, including reduced sample requirements and small packaging.     

LP-based heuristics for scheduling chemical batch processes

A mixed-integer linear programming (MILP) model for scheduling chemical batch processes is presented. Since computational times are prohibitive for most problems of realistic size, a two-stage solution procedure is suggested. In the first stage, an initial solution is derived by use of a LP-based heuristic. The proposed heuristic defines a time grid that includes only a limited number of feasible periods in which a processing task is allowed to start. Thus, the size of the original multi-period MILP model is reduced in a controlled manner and optimal solutions to the relaxed model are obtained within reasonable computational time. The second stage consists of an improvement step that aims to compress the initial schedule by left-shifting operations over the time-axis. In order to evaluate the applicability of the heuristics a number of numerical experiments were performed. It is shown that near-optimal solutions are obtained for largesize problems with only modest computational effort.     

Multilayer polymer microchip capillary array electrophoresis devices with integrated on-chip labeling for high-throughput protein analysis

It is desirable to have inexpensive, high-throughput systems that integrate multiple sample analysis processes and procedures, for applications in biology, chemical analysis, drug discovery, and disease screening. In this paper, we demonstrate multilayer polymer microfluidic devices with integrated on-chip labeling and parallel electrophoretic separation of up to eight samples. Microchannels were distributed in two different layers and connected through interlayer through-holes in the middle layer. A single set of electrophoresis reservoirs and one fluorescent label reservoir address parallel analysis units for up to eight samples. Individual proteins and a mixture of cancer biomarkers have been successfully labeled on-chip and separated in parallel with this system. A detection limit of 600 ng/mL was obtained for heat shock protein 90. Our integrated on-chip labeling microdevices show great potential for low-cost, simplified, rapid, and high-throughput analysis.