Guolin Xu

Adhesive bonding with SU-8 at wafer level for microfluidic devices

The present work proposes an adhesive bonding technique, at wafer level, using SU-8 negative photoresist as intermediate layer. The adhesive was selective imprint on one of the bonding surface. The main applications are in microfluidic area where a low temperature bonding is required. The method consists of three major steps. First the adhesive layer is deposited on one of the bonding surface by contact imprinting from a dummy wafer where the SU-8 photoresist was initially spun, or from a Teflon cylinder. Second, the wafers to be bonded are placed in contact and aligned. In the last step, the bonding process is performed at temperatures between 100 O C and 200 O C, a pressure of 1000 N in vacuum on a classical wafer bonding system. The results indicate a low stress value induced by the bonding technique. In the same time the process presents a high yield: 95-100%. The technique was successfully tested in the fabrication process of a dielectrophoretic device.

A Dielectrophoretic Chip With a 3-D Electric Field Gradient

This paper presents the design, fabrication and testing of a new structure of dielectrophoresis (DEP) chip having a three-dimensional (3-D) electric field gradient and an asymmetric distribution of the electric field in the vertical plane. This achievement was possible due to the special configuration of the electrodes: a bulk silicon electrode and a thin amorphous silicon electrode. The thick electrode defines, at the same time, the walls, while the two glass dies form the ceiling and floor of the microfluidic channel. The top glass die presents two etch-through inlet/outlet holes of the microfluidic channel. In the bottom glass die, isotropic via-holes are performed through the glass for the lead-outs. For this reason, the lead-outs does not generate fluidic leakage. Using a single material for the electrodes, the electrochemical effect for conventional multilayer metal electrodes is eliminated. The proposed DEP structure, with thin and thick electrodes, generates in the vertical plane an asymmetric distribution of the electric field and, therefore, an enhanced electric field gradient. As a result, for positive DEP, the particles are trapped near the thin electrode, while for negative DEP the particles are levitated. Compared with typical planar DEP devices, the proposed DEP structure, presents an increased DEP force in the vertical direction. As a result, the same trapping or levitation effect can be achieved at a lower voltage and, in this way, with a reduced heating of the solution. Using the bulk electrode for definition of the microfluidic channel, the need for a separate channel wall material is eliminated. The DEP device is wafer level packaged (being fully fabricated at wafer level using batch processes) therefore, can be consider as a low cost solution. The good isolating properties of the glass confer the opportunity of working at a high frequency range. Yeast cells have been used to successfully test the performance of the device: the trapping using positive DEP occurred on the bottom of the channel near the thin electrode, while the negative DEP generate a suspension of the cells 35-40 mum from the bottom

Dielectrophoretic field-flow method for separating particle populations in a chip with asymmetric electrodes

This paper presents a field-flow method for separating particle populations in a dielectrophoretic (DEP) chip with asymmetric electrodes under continuous flow. The structure of the DEP device (with one thick electrode that defines the walls of the microfluidic channel and one thin electrode), as well as the fabrication and characterization of the device, was previously described. A characteristic of this structure is that it generates an increased gradient of electric field in the vertical plane that can levitate the particles experiencing negative DEP. The separation method consists of trapping one population to the bottom of the microfluidic channel using positive DEP, while the other population that exhibits negative DEP is levitated and flowed out. Viable and nonviable yeast cells were used for testing of the separation method.

Continuous field-flow separation of particle populations in a dielectrophoretic chip with three dimensional electrodes

This letter presents a dielectrophoretic(DEP)separation method of particles under continuous flow. The method consists of flowing two particle populations through a microfluidic channel, in which the vertical walls are the electrodes of the DEPdevice. The irregular shape of the electrodes generates both electric field and fluid velocity gradients. As a result, the particles that exhibit negative DEP can be trapped in the fluidic dead zones, while the particles that experience positive DEP are concentrated in the regions with high velocity and collected at the outlet. The device was tested with dead and living yeast cells.

Characterization of deep wet etching of glass

This paper presents a characterization of wet etching of glass in HF-based solutions with a focus on etching rate, masking layers and quality of the generated surface. The first important factor that affects the deep wet etching process is the glass composition. The presence of oxides such as CaO, MgO or Al2O3 that give insoluble products after reaction with HF can generate rough surface and modify the etching rate. A second factor that influences especially the etch rate is the annealing process (560°C / 6 hours in N2 environment). For annealed glass samples an increase of the etch rate with 50-60% was achieved. Another important factor is the concentration of the HF solution. For deep wet etching of Pyrex glass in hydrofluoric acid solution, different masking layers such as Cr/Au, PECVD amorphous silicon, LPCVD polysilicon and silicon carbide are analyzed. Detailed studies show that the stress in the masking layer is a critical factor for deep wet etching of glass. A low value of compressive stress is recommended. High value of tensile stress in the masking layer (200-300 MPa) can be an important factor in the generation of the pinholes. Another factor is the surface hydrophilicity. A hydrophobic surface of the masking layer will prevent the etching solution from flowing through the deposition defects (micro/nano channels or cracks) and the generation of pinholes is reduced. The stress gradient in the masking layer can also be an important factor in generation of the notching defects on the edges. Using these considerations a special multilayer masks Cr/Au/Photoresist (AZ7220) and amorphous silicon/silicon carbide/Photoresist were fabricated for deep wet etching of a 500 μm and 1mm-thick respectively Pyrex glass wafers. In both cases the etching was performed through wafer. From our knowledge these are the best results reported in the literature. The quality of the generated surface is another important factor in the fabrication process. We notice that the roughness of generated surface can be significantly improved by adding HCl in HF solution (the optimal ratio between HF (49%) and HCl (37%) was 10/1).

A NON-CONTACT MICRO THERMOCYCLING CHIP FOR POLYMERASE CHAIN REACTIONS

A micro thermocycling chip has been developed, which is able to achieve high heating and cooling rates of over 16°C/s and 9.6°C/s respectively using the induction heating method. The heating element of the micro thermocycler was fabricated through electroplating on glass. SU-8 and Polydimethyl-siloxane (PDMS) are used to form the reaction chamber. DSP base servo controller was selected for close loop control the reaction chamber temperature. The thermocycler chips properties, such as non-contact heating method, rapid cycling speed and PC control, make it suitable to integrate into clinical molecular diagnostic devices and point-of-care devices.

A self-contained polymeric cartridge for automated biological sample preparation

Sample preparation is one of the most crucial processes for nucleic acids based disease diagnosis. Several steps are required for nucleic acids extraction, impurity washes, and DNA/RNA elution. Careful sample preparation is vital to the obtaining of reliable diagnosis, especially with low copies of pathogens and cells. This paper describes a low-cost, disposable lab cartridge for automatic sample preparation, which is capable of handling flexible sample volumes of 10 μl to 1 ml. This plastic cartridge contains all the necessary reagents for pathogen and cell lysis, DNA/RNA extraction, impurity washes, DNA/RNA elution and waste processing in a completely sealed cartridge. The entire sample preparation processes are automatically conducted within the cartridge on a desktop unit using a pneumatic fluid manipulation approach. Reagents transportation is achieved with a combination of push and pull forces (with compressed air and vacuum, respectively), which are connected to the pneumatic inlets at the bottom of the cartridge. These pneumatic forces are regulated by pinch valve manifold and two pneumatic syringe pumps within the desktop unit. The performance of this pneumatic reagent delivery method was examined. We have demonstrated the capability of the on-cartridge RNA extraction and cancer-specific gene amplification from 10 copies of MCF-7 breast cancer cells. The on-cartridge DNA recovery efficiency was 54-63%, which was comparable to or better than the conventional manual approach using silica spin column. The lab cartridge would be suitable for integration with lab-chip real-time polymerase chain reaction devices in providing a portable system for decentralized disease diagnosis.

Dielectrophoretic chip with bulk silicon electrodes

In this work we present the dielectrophoretic structure fabricated using two glass wafers and one 0.5 mm thick and highly conductive silicon wafer. In fabricated device the DEP force extends uniformly across the volume of the microfluidic device in the direction normal to the wafer plane. This is achieved by fabricating microfluidic channel walls from doped silicon so that they can also function as DEP electrodes. The advantages of the structure are: electrical leadouts that are free from the fluid leakage usually associated with the lead out recesses, a volume DEP force for deep chambers compared with the surface forces achieved by planar electrodes, no electrical dead volumes as encountered above the thin planar electrodes of alternative technologies, biocompatible silicon oxide passivated surfaces, and no electrochemical effects that arise from edge effects in multi-metal electrodes such as Ti/Au or Cr/Au.

A DISPOSABLE SELF-PRIMING AND BUBBLE TOLERANCE PNEUMATIC ACTUATION MICRO-PUMP

A low cost, robust, self-priming and bubble tolerance pneumatically actuated planar micro-pump was demonstrated and characterized. This micro-pump has a simple three-layered structure. The two micro-pump housings were fabricated with polycarbonate, while the actuation membrane which, also acted as the inlet and outlet valves was made form polydimethylsiloxane(PDMS). PDMS displayed desirable mechanical properties including very low Youngs modulus, high elongation, biocompatibility and good sealing for the design of this micropump. The use of PDMS as actuation memberanes solved problems of sealing and poor compression ratio associated with most silicon based micro-pumps. Furthermore, polycarbonate material is much easier and cheaper to fabricate than silicon wafer. Using external compressed air and vacuum source for atuation, flow rate near to 1000ul/min of air or liquid has been achieved. The maximum pump head of more than 2m is obtained with water as pumping media. The pump exhibited a linear output flow rate, insensitive to output pressure.

Enhanced cell trapping throughput using DC-biased AC electric field in a dielectrophoresis based fluidic device with densely packed silica beads.

This paper presents the use of DC‐biased AC electric field for enhancing cell trapping throughput in an insulator‐based dielectrophoretic (iDEP) fluidic device with densely packed silica beads. Cell suspension is carried through the iDEP device by a pressure‐driven flow. Under an applied DC‐biased AC electric field, DEP trapping force is produced as a result of non‐uniform electric field induced by the gap of electrically insulating silica beads packed between two mesh electrodes that allow both fluid and cells to pass through. While the AC component is mainly to control the magnitude of DEP trapping force, the DC component generates local electroosmotic (EO) flow in the cavity between the beads and the EO flow can be set to move along or against the main pressure‐driven flow. Our experimental and simulation results show that desirable trapping is achieved when the EO flow direction is along (not against) the main flow direction. Using our proposed DC‐biased AC field, the device can enhance the trapping throughput (in terms of the flowrate of cell suspension) up to five times while yielding almost the same cell capture rates as compared to the pure AC field case. Additionally, the device was demonstrated to selectively trap dead yeast cells from a mixture of flowing live and dead yeast cells.