Martina Daub

A floating 3D silicon microprobe array for neural drug delivery compatible with electrical recording

This paper reports on the design, fabrication, assembly and characterization of a three-dimensional silicon-based floating microprobe array for localized drug delivery to be applied in neuroscience research. The microprobe array is composed of a silicon platform into which up to four silicon probe combs with needle-like probe shafts can be inserted. Two dedicated positions in the array allow the integration of combs for drug delivery. The implemented comb variants feature 8 mm long probe shafts with two individually addressable microchannels incorporated in a single shaft or distributed to two shafts. Liquid supply to the array is realized by a highly flexible 250 µm thick multi-lumen microfluidic cable made from polydimethylsiloxane (PDMS). The specific design concept of the slim-base platform enables floating implantation of the array in the small space between brain and skull. In turn, the flexible cable mechanically decouples the array from any microfluidic interface rigidly fixed to the skull. After assembly of the array, full functionality is demonstrated and characterized at infusion rates from 1 to 5 µL min−1. Further, the effect of a parylene-C coating on the water vapour and osmotic liquid water transport through the PDMS cable walls is experimentally evaluated by determining the respective transmission rates including the water vapour permeability of the used PDMS type.

A versatile and flexible low-temperature full-wafer bonding process of monolithic 3D microfluidic structures in SU-8

We present a versatile fabrication process for the precise fabrication of embedded three-dimensional microfluidic structures in SU-8 photoresist. The full-wafer bond process based on a polyester (PET) handling layer enhances the previous low-temperature bonding technology. We achieved an extremely high bond strength of 45 MPa while requiring only small anchoring structures. Small channel structures with an aspect ratio >2 as well as wide membranes with an aspect ratio 80%) and enables the integration of microelectronics. The flexibility of the fabrication process is presented in two contrary applications. A completely freestanding and transparent SU-8 foil with a thickness of 225 µm featuring embedded 3D microchannels was fabricated. Also, high quality ink-jet dispensers were successfully fabricated whereas the dispenser quality mainly depends on the channel quality.

Droplet release in a highly parallel, pressure driven nanoliter dispenser

For the first time we report about the correlation between satellite free droplet release and liquid viscosity in a highly parallel, pressure driven nanoliter dispenser. In extensive studies we found that for liquids of different viscosities the length of the pressure pulse is the predominant effect compared to pressure amplitude. This result is of essential importance when actuation parameters have to be adopted for different media like oligonucleotide, DNA or protein solutions as it is the case for the non-contact high-throughput fabrication of microarrays. For each used printing buffer we found the CV to be better than 1 % within one single dispensing channel and 1.5 % within all 24 channels at a pitch of 500 /spl mu/m.

An improved 24 channel picoliter dispenser based on direct liquid displacement

For the first time we present a systematic study concerning the relation between nozzle diameter and ejected droplet volume of a highly parallel picoliter dispenser. Such dispensers are essential parts for the mass fabrication of microarrays and are able to dispense up to 96 different reagents at a pitch of 500 /spl mu/m simultaneously. In contrast to an earlier design we investigated different nozzle diameters. The change from 35 /spl mu/m to 60 /spl mu/m in nozzle diameter resulted in a doubling of dispensed volume for most used elastomers and irrespective of actuation parameters. Minimum and maximum of dispensed volumes have been determined to be 125 pl and 1700 pl. Those results are based on a new design, which also includes passive microstructures for droplet homogeneity as well as modified microchannels for improved priming and prevention of cross-contamination. Based on this, the CV of droplet velocity could be reduced from 50% down to less than 5%. The CV of droplet volume is clearly below the measurement error (8%).

Bubble-free priming of blind channels

Capillary liquid transport is an enormously powerful tool and is commonly used for directing fluids without need for any external actuation. In blind channels air pockets prevent complete capillary filling, because air cannot escape out of the channel. In this paper we present for the first time a 2-level microchannel structure, which allows complete capillary filling of blind channels without trapping air. Filling of 29 different designs with different liquids was systematically investigated by an extensive test procedure. Each design was tested at least 400 times. Certain designs showed bubble-free, successful fillings in all experiments (100% yield).

Wafer-level packaging and laser bonding as an approach for silicon-into-lab-on-chip integration

A novel approach for the integration of silicon biosensors into microfluidics is presented. Our approach is based on wafer-level packaging of the silicon die and a laser-bonding process of the resulting mold package into a polymer-multilayer stack. The introduction of a flexible and 40 μm thin hot melt foil as an intermediate layer enables laser bonding between materials with different melting temperatures, where standard laser welding processes cannot be employed. All process steps are suitable for mass production, e.g. the approach does not involve any dispensing steps for glue or underfiller. The integration approach was demonstrated and evaluated regarding process technology by wafer-level redistribution of daisy chain silicon dies representing a generic biosensor. Electrical connection was successfully established and laser-bonding tensile strength of 5.7 N mm−2 and burst pressure of 587 kPa at a temperature of 100 °C were achieved for the new material combination. The feasibility of the complete packaging approach was shown by the fabrication of a microfluidic flow cell with embedded mold package.

The Way to High Volume Fabrication of Lab-on-a-Chip Devices—A Technological Approach for Polymer Based Microfluidic Systems with Integrated Active Valves and Pumps

We present a technology platform suitable for the mass production of laboratory-on-a-chip devices made of polymers with integrated active and passive components. The presented microfluidic platform with integrated valves and pumps for active flow management is realized with three layers consisting of two polymer parts separated by a thin elastic TPE (thermoplastic elastomer) membrane welded together in one step. The elastic TPE membrane acts as an integrated deflectable membrane layer between the two outer polymer layers, each made of a weldable thermoplastic polymer (polycarbonate). Valving is realized by applying pressure in a displacement chamber above a hydraulic channel causing the membrane to deform and to seal the channel. A pump is fabricated using a displacement chamber with a valve on the inlet and outlet. The presented components, namely valve and pump, show excellent behavior regarding response time, sealing quality, and pump rate needing only a low actuation pressure. The three-layer-stack is...

PCR-slide: a modular and cascadable platform for DNA sample processing with integrated nanolitre dosage

For the first time we present a novel DNA sample processing platform with an integrated nanolitre dosage unit for extraction of processed materials in nanolitre quantities. A unique feature of the new platform is the possibility to link several sample processing steps including dilution/titration without any need for external pipetting equipment except for sample loading. This has been demonstrated by using the oligonucleotide ligase assay (OLA) coupled to the polymerase chain reaction (PCR), a sequence which requires a 1:15 dilution of OLA in PCR.

Laser micromachining as a metallization tool for microfluidic polymer stacks

A novel assembly approach for the integration of metal structures into polymeric microfluidic systems is described. The presented production process is completely based on a single solid-state laser source, which is used to incorporate metal foils into a polymeric multi-layer stack by laser bonding and ablation processes. Chemical reagents or glues are not required. The polymer stack contains a flexible membrane which can be used for realizing microfluidic valves and pumps. The metal-to-polymer bond was investigated for different metal foils and plasma treatments, yielding a maximum peel strength of Rps = 1.33 N mm−1. A minimum structure size of 10 µm was determined by 3D microscopy of the laser cut line. As an example application, two different metal foils were used in combination to micromachine a standardized type-T thermocouple on a polymer substrate. An additional laser process was developed which allows metal-to-metal welding in close vicinity to the polymer substrate. With this process step, the reliability of the electrical contact could be increased to survive at least 400 PCR temperature cycles at very low contact resistances.

Integrated process control for highly parallel and contact-free micro array printing

This paper reports for the first time on an integrated process control of a highly parallel non-contact dispenser for microarray production. Monitoring the fundamental process parameters has become indispensable because of significantly increased demands on high quality microarrays. We integrated a pressure sensor in our pneumatically actuated dispenser to acquire the transient pressure pulse during droplet ejection. This enables the total process control for the dispenser and with it the adoption of operation parameters for varying liquid properties, like viscosity, surface tension and density. We optimised pressure parameter and the geometry of the actuation chamber. This made it possible to dispense liquid viscosities up to 10.8 mPas (four fold improvement) at frequencies up to 30 Hz (15 fold improvement) for all tested liquids. In addition, the integrated pressure sensor allows to detect failure modes, like flooded actuation chamber or empty printhead nozzles, leading to a higher quality of the fabricated microarrays.