Channel Of Microfluidic Chip Research Articles

Study on a differential pressure microflow sensor on microfluidic chip

Based on the principle of differential pressure flow measurement, graphene film was used to measure the differential pressure in the micro channel of microfluidic chip and finally to obtain the micro flow rates. The relationship between differential pressure and flow rate in micro channel was studied and validated by CFD simulation. The fiber F-P cavity using graphene film was fabricated as the pressure sensitive structure, and the relationship between the measured pressure and the optical power output from the pressure sensitive structures was studied. The mechanism model used to measure the micro flow rates in the micro channel of microfluidic chip was established, and a sample of micro flow sensor was fabricated. The relationship between various quantities in the process of converting flow rate to optical power was verified through experiments, and the mechanism model established was verified. The experimental results demonstrate that fabricated sample could achieve accurate measurement of micro flow rate in the micro channel of microfluidic chip.

Recent advances in isolation and detection of circulating tumor cells with a microfluidic system

循环肿瘤细胞(CTCs)的分离分析一直是肿瘤相关研究中的热点方向,作为液体活检的重要标志物之一,其在外周血中的含量与癌症病发状况密切相关。然而人体血液中CTCs的含量非常低,通常来说仅有0~10个/mL,因此在开展临床血液样本中CTCs的检测前,往往需要对样本进行前处理,以实现CTCs的分离和富集。微流控芯片技术凭借样品消耗少,分离效率高,易于自动化和集成化等特点,在CTCs分离分析研究中具有诸多优势。近年来,利用微流控芯片开展CTCs分离检测的研究进展迅速,多种技术原理和检测方法相继出现。从技术原理角度进行区分,可分为生物亲和法和物理筛选法。生物亲和法主要依赖抗原抗体相互作用,或核酸适配体与靶标的特异性结合,该方法选择性高,但效率和捕获率偏低。物理筛选法则主要依据细胞本身的物理性质,诸如尺寸、密度和介电性质等差异实现分离。例如,可通过芯片微结构对CTCs进行阻隔或捕获,通过外加物理场(声、电、磁)辅助分选,也可以利用微观尺度流体力学作用对混合细胞进行筛分。物理筛选法一般通量较高,但往往分离纯度较低。同时,利用微流控芯片的集成优势将两种方法相结合,往往能得到更好的分离效果。除了以CTCs作为直接目标的正向富集外,还可以采取反向富集的策略,通过将作为干扰项的白细胞等作为靶标进行选择性地去除,可以避免直接筛选方式对CTCs细胞活性产生的影响。该文概述性介绍了利用微流控芯片开展循环肿瘤细胞分离检测的技术原理、芯片原位检测方法和研究进展,并结合现阶段存在的问题对其未来发展趋势予以展望。

A Visible-Light-Powered Polymerization Method for the Immobilization of Enantioselective Organocatalysts into Microreactors.

A versatile one‐step photopolymerization approach for the immobilization of enantioselective organocatalysts is presented. Chiral organocatalyst‐containing monoliths based on polystyrene divinylbenzene copolymer were generated inside channels of microfluidic chips. Exemplary performance tests were performed for the monolithic Hayashi–Jørgensen catalyst in continuous flow, which showed good results for the Michael addition of aldehydes to nitroalkenes in terms of stereoselectivity and catalyst stability with minimal consumption of reagents and solvents.

Quantum Dot-Bead-DNA Probe-Based Hybridization Fluorescence Assays on Microfluidic Chips.

The development of chip-based, quantum dot (QD)-bead-DNA conjugate probes for hybridization detection is a prime research focus in the field of microfluidics. QD-Bead-DNA probe-based hybridization detection methods are often called "bead-based assays," and their success is substantially influenced by the dispensing and manipulation capabilities of microfluidic technology. Met was identified as a prognostic marker in different cancers including lung, renal, liver, head and neck, stomach, and breast. In this report, the cancer causing Met gene was detected with QDs attached to polystyrene microbeads. We constructed a microfluidic platform using a flexible PDMS polymer. The chip consists of two channels, with two inlets and two outlets. The two channels were integrated with QD-bead-DNA probes for simultaneous detection of wild type target DNA and mutant DNA, containing three nucleotide changes compared to the wild type sequence. The fluorescence quenching ability of QDs within the channels of microfluidic chips were compared for both DNAs.

Detection of DNAs by Using Dual Packed Polystyrene Bead-Quantum Dots in a Microfluidic Chip.

The semiconductor nanocrystals (or quantum dots) have shown peculiar optical and electrical properties due to their exceptionally small size. In recent years, tremendous researches on quantum dots have been carried out. Among them, QDs as sensing media for biological assay have achieved a great progress. Recently we have reported the detection of DNAs by using fluorescence quenching of QDs after DNA hybridization. Several oligonucleotides and human genomic genes could be detected. In this report we used dual packing of polystyrene bead-quantum dots to detect different kinds of DNAs simultaneously. QDs with different emission peaks were used. Carboxylated-CdSe/ZnS QDs (emission: 525, 605 nm) could bind to microbeads of polystyrene/divinyl benzene via EDC/NHS cross-linking reaction. Polystyrene bead-QDs with different colors were packed in the channel of the microfluidic chip. The fluorescence quenching from the QDs by intercalating dye was observed after hybridization of exon 6 and 7 of p53 gene at the weir in the channel of microfluidic chip. The simultaneous fluorescence quenching of the QDs by PI and TOTO-3 were observed.

Combination of capillary micellar liquid chromatography with on-chip microfluidic chemiluminescence detection for direct analysis of buspirone in human plasma

Microfluidic based chemiluminescence (CL) detector having novel channel design for enhanced mixing has been developed and investigated in terms of its applicability with micellar mode of liquid chromatography (MLC). The newly developed detector was found to be highly sensitive and an alternative detection technique to combine with capillary MLC. This combination was successfully employed for direct detection of a model analyte using Ru(III)-peroxydisulphate CL system. The selected analyte, buspirone hydrochloride (BUS), was detected selectively at therapeutic concentration levels in human plasma without any sample pretreatment. By incorporating eight flow split units within the spiral channel of microfluidic chip, an enhancement of 140% in CL emission was observed. We also evaluated the effect of non- ionic surfactant, Brij-35, which used as mobile phase modifier in MLC, on CL emission. The CL signal was improved by 52% compared to aqueous-organic mobile phase combinations. Various parameters influencing the micellar chromatographic performance and the CL emission were optimized. This allowed highly sensitive analysis of BUS with limit of detection (LOD) of 0.27ngmL−1 (3σ/s) and limit of quantification (LOQ) of 0.89ngmL−1 (10σ/s). The analyte recovery from human plasma at three different concentration level ranges from 88% to 96% (RSD 1.9–5.3%). The direct analysis of BUS in human plasma was achieved within 6min. Therefore, combining microfluidic CL detection with micellar mode of separation is an efficient, cost-effective and highly sensitive technique that can utilize MLC in its full capacity for various bioanalytical procedures.

Detection of <I>K</I>-Ras Oncogene Using Magnetic Beads-Quantum Dots in Microfluidic Chip

Recently quantum dots (QDs) have been extensively used in the field of biotechnology. QDs have merits of wide selection of emission wavelength and exceptional stability against photo bleaching over conventional organic fluorophores and are used in cell imaging, biomarker, and fluorescence resonance energy transfer (FRET) sensor. Magnetic beads have been used as solid support in microfluidic devices to trace bio-molecules. In this study, Polydimethylsiloxane (PDMS) based microfluidic chips were prepared for the detection of K-Ras oncogene by using QDs-DNA conjugate. K-Ras oncogene can be detected by fluorescence quenching in microfluidic chip. Carboxylated CdSe/ZnS QDs (emission wavelength: 605 nm) could bind to magnetic beads of polystyrene/divinyl benzene via EDC/NHS crosslinking reaction. The fluorescence from QDs could be quenched by intercalating dye (thiazol orange dimers: TOTO-3) after hybridization with target DNA and probe DNA in the channel of microfluidic chip. The fluorescence intensity change of QDs after hybridization in microfluidic chip has been studied.

The Detection of <I>p</I>53 Gene via Fluorescence Quenching of Quantum Dot in Microfluidic Chip

Recently, quantum dot (QD) has been used widely in the field of bio assay including cell imaging, biomarker, and fluorescence resonance energy transfer (FRET) sensor. The DNA assay without labeling process has several advantages including low cost, short time, and simplicity. Microbeads of agarose, glass, and polystyrene have been used as a solid support in microfluidic devices to trace molecules. The main advantages of microfluidics include high throughput, short analysis time, small sample volume, and high sensitivity. PDMS based microfluidic chips were prepared for the detection of p53 gene by using QD-DNA conjugate. The microfluidic chip has a weir in the channel to trap microbeads to which QD-DNA probes bind. Carboxylated CdSe/ZnS QDs (wavelength of emission: 605 nm) could bind to microbeads of polystyrene/divinyl benzene via EDC/NHS crosslinking reaction. The target gene and DNA intercalating dye (TOTO-3) were loaded into the micro-channel. Fluorescence quenching from QDs by intercalating dye was observed after hybridization of DNA at the weir in the channel of microfluidic chip. The fluorescence quenching from QDs by TOTO-3 was dependent on the concentration of target gene. This experiment shows the possibility of rapid detection of DNA via bead-QD complex on microfluidic chip.

A low-cost, manufacturable method for fabricating capillary and optical fiber interconnects for microfluidic devices

Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels. UV light is manually directed onto the ends of the interconnects using a microscope. UV-curable glue is then allowed to wick to the end of the capillaries, fibers, or wires, where it is cured to form rigid, liquid-tight connections. In a variant of this technique, used with light-guiding capillaries and optical fibers, the UV light is directed into the capillaries or fibers, and the UV-glue is cured by the cone of light emerging from the end of each capillary or fiber. This technique is fully self-aligned, greatly improves both the quality and the manufacturability of the interconnects, and has the potential to enable the fabrication of interconnects in a fully automated fashion. Using these methods, including a semi-automated implementation of the second technique, over 10,000 interconnects have been formed in almost 2000 microfluidic chips made of a variety of rigid materials. The resulting interconnects withstand pressures up to at least 800psi, have unswept volumes estimated to be less than 10 femtoliters, and have dead volumes defined only by the length of the capillary.

Glass wafers bonding via Diels–Alder reaction at mild temperature

In this paper, we introduced a novel bonding method of glass wafers by Diels–Alder reaction at mild temperature. After standard hydroxylization and aminosilylation, two wafers were modified by 2-furaldehyde and maleic anhydride, respectively. Then they were brought into close contact and tightly held with a clamping fixture. A strong bonding could be achieved by annealing for 5 h at 200 °C. Bonding strength is as high as 1.78 MPa and sufficient for most application of microfluidic chips. This bonding process has the advantages of simple operation and good smoothness of the wafer surface. Mild temperature can prevent the channel of microfluidic chip distorted or collapse and shorten the cooling time.

Measurement of Channel Depth by Using a General Microscope Based on Depth of Focus

This paper presents a simple and rapid method to measure the depth of the channel of microfluidic chip. With the depth of focus (DOF) low to few micro-meters, general microscopes show the strong axial (or longitudinal) resolving power. With the assistant of fine-adjustment, the objective was controlled accurately to focus on the channel side and channel bed respectively. Then the depth was calculated from the scales that fine adjustments turned. Experiments results demonstrated the possibilities of depth measurement with normal microscope. Compared with other methods, this method showed high degree of precision with a deviation less than 0.6µm while the magnification was 100X. This method is rapid, simple and reliable, and it is very suitable for monitoring the etching process to optimize the function of microfluidic chip.

Fabrication of DNA purification microchip integrated with mesoporous matrix based on MEMS technology

This paper presents a novel microfabricated DNA purification microfluidic chip with enhanced performance based on the principle of micro solid phase extraction. The microchip comprises a layer of mesoporous material as solid phase matrix which is fabricated on the internal wall of the channel of microfluidic chip by electrochemical etching Si in an electrolyte. The conditions of electrochemical etching and porosity of the mesoporous matrix have been investigated. The properties of mesoporous matrix have been characterized by scanning electron microscopy and by BET (Brunauer, Emmet, and Teller) nitrogen adsorption analysis. The pore size of the mesoporous matrix is in the range of 10–30 nm, and the surface area is about 300 m2/g. Compared with the microfluidic chips with micropillar array matrix or non-porous matrix, the microchip with mesoporous matrix is able to extract enough polymerase chain reaction-amplifiable DNA from cultures of rat mesenchymal stem cells in 20 min. This highly efficient, effortless, and flexible technology can be used as a lab-on-a-chip component for initial biologic sample preparation.

Investigation on micro-modification mechanism on surface of microfluidic glass chip

The surface of the glass channel of microfluidic chip is treated with dichlorodimethylsilan. After the treatment, the silicon hydroxyl on the surface of the glass channel is silylated, which results in the reduction or even the elimination of the electroosmotic flow. Furthermore, full-potential linear-muffin-tin-orbital molecular dynamics method is used to investigate the micro -mechanism of surface reaction theoretically. The calculation results indicate that the hydrogen atom in silicon hydroxyl binds with the chlorine atom in dichlorodimethylsilan to form a stable HCl molecule and goes off, thereby the surface of the channel is covered with silylane.

Microfabrication and characterization of porous channels for DNA purification

The present work demonstrates the availability of using porous channels of microfluidic chips as a solid phase matrix for extracting DNA from whole blood. Two kinds of porous channels were microfabricated by MEMS technology and anodization technology. The anodization process of porous channels was investigated and optimized. Porous channels were characterized, and a porous rectangle channel showed a more uniform and stable feature related to a porous V-type channel. The optimal porous rectangle channel was further used for purifying DNA, which showed a higher DNA recovery than the non-porous one. Optimization of the DNA elution condition established a higher DNA extracted efficiency at 55 °C than at 25 °C or at 70 °C. The time consumed in the incubation process for eluting DNA could be reduced by increasing the flow rate of the washing step. Compared to commercial kits, the porous rectangle channel under optimal conditions could extract two-fold amounts of PCR-amplifiable DNA from whole blood in 15 min. This highly efficient, effortless and flexible technology can be used as a lab-on-a-chip component for initial biologic sample preparation.