Dafu Cui

An integrated biochip design and fabrication

Polymerase chain reaction (PCR) microvessel, capillary electrophoresis (CE) microchannel and impedance electrodes were integrated in a monolithic biochip. This paper reports on the detailed designs and fabrications of the PCR-CE-detector integrated biochip. The CE microchannel and PCR microvessel were fabricated with PDMS poured on a master made by SU-8 photoresist. The electrode plate was integrated with Au heater and temperature sensor for PCR amplification, electrodes for CE separation and impedance detection. The structure of the microfluidic channel was introduced and the impedance of microelectrodes on the chip was simulated.

On‐line cell lysis and DNA extraction on a microfluidic biochip fabricated by microelectromechanical system technology

Integrating cell lysis and DNA purification process into a micrototal analytical system (μTAS) is one critical step for the analysis of nucleic acids. On‐chip cell lysis based on a chemical method is realized by sufficient blend of blood sample and the lyzing reagent. In this paper two mixing models, T‐type mixing model and sandwich‐type mixing model, are proposed and simulation of those models is conducted. Result of simulation shows that the sandwich‐type mixing model with coiled channel performs best and this model is further used to construct the microfluidic biochip for on‐line cell lysis and DNA extraction. The result of simulation is further verified by experiments. It asserts that more than 80% mixing of blood sample and lyzing reagent which guarantees that completed cell lysis can be achieved near the inlet location when the cell/buffer velocity ratio is less than 1:5. After cell lysis, DNA extraction by means of a solid‐phase method is implemented by using porous silicon matrix which is integrated in the biochip. During continuous flow process in the microchip, rapid cell lysis and PCR‐amplifiable genomic DNA purification can be achieved within 20 min. The potential of this microfluidic biochip is illustrated by pretreating a whole blood sample, which shows the possibility of integration of sample preparation, PCR, and separation on a single device to work as portable point‐of‐care medical diagnostic system.

Microfluidic Biochip for Blood Cell Lysis

Abstract Based on the micro-electro-mechanical system (MEMS) technology, a sandwich flow microfluidic biochip for blood cell lysis was designed and fabricated. The cell solution was sandwiched in between the chemical reagent solution, and both were introduced into the biochip. The two solutions were then flowing through the microchannel of the biochip. Finally, cells lysis was brought about by complete blend of the cell solution and the chemical reagent solution during continuous flow. Rat blood with anticoagulant was the cell sample, while guanidine and Triton X-100 were used as the lysing reagents, respectively, and the effects of the two reagents on cell lysis were compared. The effects of the cell concentration and the flow rate on cell lysis were analyzed using guanidine as the lysing reagent. Blood cells can be lysed in a few minutes when the flow rate of the lysing reagent is considerably faster than the flow rate of the cell sample. Blood cells can be rapid lysed in microfluidic biochip when the flow rates of the lysing reagent and the cell sample are increased simultaneously in the above proportion. The sandwich-type microfluidic biochip for cell lysis potentially integrated with the biochip for cell separation and the biochip for DNA extraction could enable complete pretreatment of complex biologic samples, which can lay the foundation for the realization of the micro total analytic system (μ TAS).

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.

Use of surface plasmon resonance to investigate lateral wall deposition kinetics and properties of polydopamine films

Dopamine (DA) is a particularly important neurotransmitter. Polydopamine (pDA) films have been demonstrated to be important materials for the immobilization of biomolecules onto almost any type of solid substrate. In this study, a surface plasmon resonance (SPR)-based sensor system with the sensor chip surface parallel to the direction of gravity was used to investigate the lateral wall deposition kinetics and properties of pDA films. The deposition kinetics of pDA Films are limited by the oxidation process. The pDA film could not be removed from the sensor chip completely by a strongly alkaline solution, indicating that the pDA film was heterogeneous in the direction of deposition. The pDA film formed near the interior of the solution was less stable than the film formed near the gold-solution interface. Adsorption of proteins on pDA film was studied compared with that on bare gold and dextran sensor chip. The reduction of Au(111) cations by the pDA film, forming a layer of gold particles, was monitored using SPR.

Design, fabrication and characterization of nano-filters in silicon microfluidic channels based on MEMS technology

Since most clinical assays are performed on cell‐free serum or plasma, micro‐analytical systems for blood tests require integrated on‐chip microfluidics for the isolation of plasma or serum from crude blood samples. In this paper, we present a crossflow filtration method using novel silicon nano‐filters for plasma separation. The microfluidic chip is made of a silicon substrate containing micropillar arrays, feed channels, side channels and nano‐gap structures, sealed with a PDMS‐glass compound cover. The design of the silicon filtration structures were optimized using numerical analysis and the optimal MEMS fabrication procedures were obtained. The filtration structures including nano‐filters were characterized using SEM and subsequently used to isolate plasma from whole blood in a continuous manner. Compared with micro‐gap structures in silicon microfluidic channels, the nano‐gap structures have been used to separate plasma from whole blood samples with higher selectivity, where a maximum plasma selectivity of 97.7% has been obtained. Common problems of clogging and jamming in filtration applications have seldom been noticed in our device. The presented microfluidic filtration device for plasma isolation could be integrated into μTAS for point‐of‐care diagnostics in the near future.

A micro gas chromatography column with a micro thermal conductivity detector for volatile organic compound analysis

In this paper, a micro gas chromatography (μGC) system contained a μGC column and a micro thermal conductivity detector (μTCD) was proposed. In order to reduce the volume of the system, some micro heaters were integrated on the surface and backside of the GC column, which could provide a robust temperature programming capability and rapidly increase the temperature of the μGC column. In addition, a silicon-glass μTCD with four-thermistor thermal conductivity cells that can offer significant advantages over previously reported designs including low dead volume, good thermal isolation, and elimination of the thermal noise was proposed in this paper. Experimental results have indicated that the μGC system with a detection limit of several ppm concentration levels separated and detected the benzene, toluene, and styrene in less than 3 min, and the μGC system also exhibited a good linear response in the test range.

Fabrication of Solid Phase Extraction DNA Chips Based on Bio-Micro-electron-Mechanical System Technology

Abstract In this work, a novel solid phase extraction (SPE) deoxyribonucleic acid (DNA) microfluidic chip with silicon-PDMS-glass structure was fabricated based on bio-micro-electro-mechanical system (BioMEMS) technology. Four kinds of solid phase matrixes were fabricated on silicon substrates, and the characteristics of these matrixes were analyzed. The porous oxidized silicon was optimally selected as the solid phase matrix for purification DNA (deoxyribonucleic acid). The different sealing technologies were contrastively developed for sealing the chip to form a close channel. The polydimethylsiloxane-glass (PDMS-glass) cover was fabricated using the optimal pressing method and the silicon substrate with the solid phase matrix was bonded with the PDMS-glass cover to accomplish the preparation of the SPE chip. This SPE chip was used successfully for purification genomic DNA from the rat whole blood. DNA of 23.5ng was extracted from per microlitre whole blood and the extracted DNA was successfully amplified by PCR, which could reach the level of the commercial DNA purification kits. Furthermore, the SPE microfluidic chips have the potential to be integrated with other sample preparation microchips, PCR microchip, capillary electrophoresis microchip and so on to achieve detection and analysis of the complex biological samples.

Thermally excited SiN beam resonant pressure sensor

A new type pressure sensor based upon an electro-thermally driven and piezo-resistively sensed SiN-beam resonator is presented. A finite element analysis (FEA) method is involved to analyze the relationship between the excitation power, thermal stress, applied pressure and the resonant frequencies of the beam. The sensor is fabricated using silicon micro- machined technology and fusion bonding. Measurements yield a fundamental frequency of about 85 kHz and Q-factor of 1000 in air at atmospheric pressure, rising to over 40,000 in high vacuum (<0.01 Pa). A special close-loop detecting technology is employed to measure the response of the resonant frequency at different applied pressure loads. A 0 - 400 kPa sensor has a good linear frequency/pressure relationship. The span is about 10 kHz over the full pressure sweep, and the pressure sensitivity is about 23.8 Hz/kPa.

SiN beam resonant pressure sensors with a novel structure

In this paper, a resonant pressure sensor has been designed and fabricated by MEMS technology which consists of a silicon nitride beam supported by a single crystal silicon frame of a special design, mounting on a silicon diaphragm by bonding. The beam is electrothermally excited and its vibrations are detected by thin film piezoresistors. Numerical modeling is performed on design of diaphragm geometry and sensitivity of pressure measurement. Both computer simulation and experimental results show that the novel structure largely increases the pressure sensitivity.