Javier Berganzo

Novel three-dimensional embedded SU-8 microchannels fabricated using a low temperature full wafer adhesive bonding

This paper describes a novel fabrication method for the manufacture of three-dimensional (3D) interconnected microchannels. The fabrication is based on a full wafer polymer bonding process, using SU-8 polymer epoxy photoresist as a structural material. The technology development includes an improvement of the SU-8 photolithography process in order to produce high uniformity films with good adhesive properties. Hence, 3D embedded microchannels are fabricated by a low temperature adhesive bonding of the SU-8 photopatterned thick films. The bonding occurs at temperatures (100–120 °C) lower than those usually applied in bonding technology. The bonding process parameters have been chosen in order to achieve a strong and void-free bond. High bond strengths, up to 8 MPa, have been obtained. Several examples using this new technology are shown, including bonding between different combinations of silicon and Pyrex wafers. This method also allows us to bond wafers with previously surface micromachined structures. Interconnected microchannels with vertical smooth walls and aspect ratios up to five have been obtained. Channels from 40 to 60 µm depth and from 10 to 250 µm width have been achieved. Liquid has been introduced at different levels into the microchannels, verifying good sealing of the 3D interconnected microchannels. The fabrication procedure described in this paper is fast, reproducible, CMOS compatible and easily implementable using standard photolithography and bonding equipment.

Fabrication of SU-8 multilayer microstructures based on successive CMOS compatible adhesive bonding and releasing steps

This paper describes a novel fabrication process based on successive wafer-level bonding and releasing steps for stacking several patterned layers of the negative photoresist EPON SU-8. This work uses a polyimide film to enhance previous low temperature bonding technology. The film acts as a temporary substrate where the SU-8 is photopatterned. The poor adhesion between the polyimide film and SU-8 allows the film to be released after the bonding process, even though the film is still strong enough to carry out photolithography. Using this technique, successive adhesive bonding steps can be carried out to obtain complex 3-D multilayer structures. Interconnected channels with smooth vertical sidewalls and freestanding structures are fabricated. Unlike previous works, all the layers are photopatterned before the bonding process yielding sealed cavities and complex three-dimensional structures without using a sacrificial layer. Adding new SU-8 layers reduces the bonding quality because each additional layer decreases the thickness uniformity and increases the polymer crosslinking level. The effect of these parameters is quantified in this paper. This process guarantees compatibility with CMOS electronics and MEMS. Furthermore, the releasing step leaves the input and the output of the microchannels in contact with the outside world, avoiding the usual slow drilling process of a cover. Hence, in addition to the straightforward integration of electrodes on a chip, this fabrication method facilitates the packaging of these microfluidic devices.

Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

The fabrication, characterization and packaging of novel microfluidic-optical integrated biosensors for label-free biochemical detection is presented in this paper. The integrated device consists of a three-dimensional embedded microchannel network fabricated using enhanced CMOS compatible SU-8 multilevel polymer technology on top of a wafer containing Mach-Zehnder Interferometer (MZI) nanophotonic biosensor devices. PMMA housing provides connection to the macro-world and ensures robust leakage-free flow operation of the devices. This macro-microfluidic module can operate at pressure drops up to 1000 kPa. Fluid flow experiments have been performed in order to demonstrate the robustness of our microfluidic devices. The devices have been designed to operate under continuous flow. Steady-state flow rates ranging from 1 to 100 µl min−1 at pressure drops ranging from 10 to 500 kPa were measured in the laminar flow regime. Experimental results are in good agreement with laminar flow theory. The first interferometric sensing measurements are presented in order to demonstrate the functionality of these novel integrated devices for lab-on-a-chip and label-free biosensing applications. A bulk refractive index detection limit of 3.8 × 10−6 was obtained, close to the minimum detected up to now by label-free biosensor devices without microfluidic integration. As far as we know, this is the first time that a label-free biosensor device is integrated within a microfluidic network using a wafer-level CMOS compatible process technology.

Study of functional viability of SU-8-based microneedles for neural applications

This paper presents the design, fabrication, packaging and first test results of SU-8-based microneedles for neural applications. By the use of photolithography, sputtering and bonding techniques, polymer needles with integrated microchannels and electrodes have been successfully fabricated. The use of photolithography for the patterning of the fluidic channel integrated in the needle allows the design of multiple outlet ports at the needle tip, minimizing the possibility of being blocked by the tissue. Furthermore, the flexibility of the polymer reduces the risk of fracture and tissue damage once the needle is inserted, while it is still rigid enough to allow a perfect insertion into the neural tissue. Fluidic and electric characterization of the microneedles has shown their viability for drug delivery and monitoring in neural applications. First drug delivery tests in ex vivo tissue demonstrated the functional viability of the needle to deliver drugs to precise points. Furthermore, in vivo experiments have demonstrated lower associated damages during insertion than those by stereotaxic standard needles.

SU-8 microprobe with microelectrodes for monitoring electrical impedance in living tissues

This paper presents a minimally invasive needle-shaped probe capable of monitoring the electrical impedance of living tissues. This microprobe consists of a 160 microm thick SU-8 substrate containing four planar platinum (Pt) microelectrodes. We design the probe to minimize damage to the surrounding tissue and to be stiff enough to be inserted in living tissues. The proposed batch fabrication process is low cost and low time consuming. The microelectrodes obtained with this process are strongly adhered to the SU-8 substrate and their impedance does not depend on frequency variation. In vitro experiments are compared with previously developed Si and SiC based microprobes and results suggest that it is preferable to use the SU-8 based microprobes due to their flexibility and low cost. The microprobe is assembled on a flexible printed circuit FPC with a conductive glue, packaged with epoxy and wired to the external instrumentation. This flexible probe is inserted into a rat kidney without fracturing and succeeds in demonstrating the ischemia monitoring.

BESOI-based integrated optical silicon accelerometer

The design, simulation, fabrication and characterization of a new integrated optical accelerometer is presented in this paper. The reduction of fabrication, packaging and thermomechanical stresses are considered by keeping the weak mechanical parts free of stresses. The mechanical sensor consists on a quad beam structure with one single mass. In addition, there are two waveguides on the frame of the chip self-aligned to one on the mass of the accelerometer. Four lateral beams increase the mechanical sensitivity and allow the flat displacement of the optical waveguides on the mass. The working principle is based on the variation of the output light intensity versus the acceleration due to the misalignment of the waveguides. The devices have been optimized by the finite-element method to obtain a mechanical sensitivity of 1 /spl mu/m/g. The fabrication technology is based on BESOI wafers combining bulk an surface micromachining. Moreover, machined glass wafers with cavities are bonded to the silicon wafer for packaging and damping control. Special packaging considerations as dicing, polishing and alignment are also presented. Optical measurements at 633 nm shown an optical sensitivity of 2.3 dB/g for negative and 1.7 dB/g for positive acceleration. This difference in the sensitivity has been demonstrated as a consequence of the passivation layer located over the core of the waveguides.

A novel Real Time micro PCR based Point-of-Care device for Salmonella detection in human clinical samples

Our POC (Point of Care) device is intended to be a diagnostic tool for routine use in the clinical sector. The validation of the whole procedure, including bacterial genomic DNA isolation and the Real Time detection of Salmonella spp., was conducted on 29 clinical stool samples that had been diagnosed with Salmonella spp. by a routine culture technique. The entire process was achieved in a single microfluidic chip within 35 min. In comparison to the culture reference method that is used in the clinical laboratories, this new device performed well in regards to the analytical parameters of sensitivity, specificity and accuracy. Therefore, the POC device reported in this study proved to be very appropriate for the fully integrated analysis system. To the best of our knowledge, this is the first work to report the sample preparation and followed by Real Time PCR (Polymerase Chain Reaction) on a single 2.5 μl chamber chip for the detection of Salmonella spp. bacteria in stool samples.

SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording

Here, we describe new fabrication methods aimed to integrate planar tetrode-like electrodes into a polymer SU-8 based microprobe for neuronal recording applications. New concepts on the fabrication sequences are introduced in order to eliminate the typical electrode-tissue gap associated to the passivation layer. Optimization of the photolithography technique and high step coverage of the sputtering process have been critical steps in this new fabrication process. Impedance characterization confirmed the viability of the electrodes for reliable neuronal recordings with values comparable to commercial probes. Furthermore, a homogeneous sensing behavior was obtained in all the electrodes of each probe. Finally, in vivo action potential and local field potential recordings were successfully obtained from the rat dorsal hippocampus. Peak-to-peak amplitude of action potentials ranged from noise level to up to 400-500 μV. Moreover, action potentials of different amplitudes and shapes were recorded from all the four recording sites, suggesting improved capability of the tetrode to distinguish from different neuronal sources.

SU-8-based microneedles for in vitro neural applications

This paper presents novel design, fabrication, packaging and the first in vitro neural activity recordings of SU-8-based microneedles. The polymer SU-8 was chosen because it provides excellent features for the fabrication of flexible and thin probes. A microprobe was designed in order to allow a clean insertion and to minimize the damage caused to neural tissue during in vitro applications. In addition, a tetrode is patterned at the tip of the needle to obtain fine-scale measurements of small neuronal populations within a radius of 100 µm. Impedance characterization of the electrodes has been carried out to demonstrate their viability for neural recording. Finally, probes are inserted into 400 µm thick hippocampal slices, and simultaneous action potentials with peak-to-peak amplitudes of 200–250 µV are detected.

SU-8 Based Microdevices to Study Self-Induced Chemotaxis in 3D Microenvironments

Tissues are complex three-dimensional structures in which cell behaviour is frequently guided by chemotactic signals. Although starvation and nutrient restriction induce many different chemotactic processes, the recreation of such conditions in vitro remains difficult when using standard cell culture equipment. Recently, microfluidic techniques have arisen as powerful tools to mimic such physiological conditions. In this context, microfluidic three-dimensional cell culture systems require precise control of cell/hydrogel location because samples need to be placed within a microchamber without obstruction of surrounding elements. In this article, SU-8 is studied as structural material for the fabrication of complex cell culture devices due to its good mechanical properties, low gas permeability and sensor integration capacity. In particular, this manuscript presents a SU-8 based microdevice designed to create “self-induced” medium starvation, based on the combination of nutrient restriction and natural cell metabolism. Results show a natural migratory response towards nutrient source, showing how cells adapt to their own microenvironment modifications. The presented results demonstrate the SU-8 potential for microdevice fabrication applied to cell culture.