Juergen Steigert

Rapid prototyping of microfluidic chips in COC

We present a novel, cost-efficient process chain for fast tooling and small-lot replication of high-quality, multi-scale microfluidic polymer chips within less than 5 days. The fabrication chain starts with a primary master which is made by well-established cleanroom processes such as DRIE or negative SU-8 resist based surface micromachining. The formation of undercuts in the master which would complicate demolding is carefully avoided. Secondary PDMS masters or epoxy-based masters which are more suitable for common polymer replication schemes such as soft-embossing, hot-embossing or injection molding are subsequently cast from the primary masters. The polymer replica are mainly made of COC and show excellent fidelity with the conventionally micromachined master while displaying no degeneration, even after more than 200 cycles. The use of other polymers such as PMMA is also possible. The process chain further includes surface modification techniques for overall, long-term stable hydrophilic coatings and for local hydrophobic patches as well as a durable sealing based on thermal bonding.

Fully integrated whole blood testing by real-time absorption measurement on a centrifugal platform

We present a novel microfluidic concept to enable a fast colorimetric alcohol assay from a single droplet of whole blood. The reduced turn-around time of 150 seconds is, on the one hand, achieved by a full process integration including metering, mixing with reagents, and sedimentation of cellular constituents. On the other hand, our novel total internal reflection (TIR) scheme allows to monitor the increase of the absorbance values in real-time. Thus, the saturation values can be predicted accurately based on an extrapolation of real-time measurements acquired during a 100 second initial period of rotation. Additionally, we present a metering structure to define nanolitre sample volumes at a coefficient of variation (CV) below 5%.

In-plane silicon probes for simultaneous neural recording and drug delivery

This paper reports on the design, fabrication and characterization of silicon-based microprobes for simultaneous neural recording and drug delivery. The fabrication technology is based on two-stage deep reactive ion etching combined with silicon wafer bonding and grinding to realize channel structures integrated in needle-like probe shafts. Liquids can be supplied to microfluidic devices via in-plane and out-of-plane ports. The liquid is dispensed at circular out-of-plane ports with a diameter of 25 µm and rectangular in-plane ports with dimensions of 50 × 50 µm2. Two-shaft probes with a pitch between shafts of 1.0 and 1.5 mm were realized. The probe shafts have a length of 8 mm and rectangular cross-sections of w × h (w = 250 µm and h = 200 or 250 µm). Each shaft contains one or two fluidic channels with a cross-section of 50 × 50 µm2. In addition, each probe shaft comprises four recording sites with diameters of 20 µm close to the outlet ports. Mechanical and fluidic characterization demonstrated the functionality of the probes. Typical infusion rates of 1.5 µL min−1 are achieved at a differential pressure of 1 kPa. The Pt-gray electrodes have an average electrode impedance of 260 ± 59 kΩ at 1 kHz.

Integrated Sample Preparation, Reaction, and Detection on a High-Frequency Centrifugal Microfluidic Platform

We extend the toolbox of lab procedures in life sciences by development of centrifugal microfluidics for high-level process integration. This is accomplished by implementing novel functional principles for sedimentation, batch-mode mixing, frequency-dependent online flow control, and optical read-out, which can be integrated into a process chain. The modular centrifugal setup comprises a microstructured disposable polymer disk as well as a reusable spinning and detection unit. We successfully developed centrifugal microfluidic technologies, which are suitable for sample preparation, process engineering, personalized diagnostics, and hematology, on this platform.

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.

Dye-based coatings for hydrophobic valves and their application to polymer labs-on-a-chip

We provide a method for the selective surface patterning of microfluidic chips with hydrophobic fluoropolymers which is demonstrated by the fabrication of hydrophobic valves via dispensing. It enables efficient optical quality control for the surface patterning thus permitting the low-cost production of highly reproducible hydrophobic valves. Specifically, different dyes for fluoropolymers enabling visual quality control (QC) are investigated, and two fluoropolymer-solvent-dye solutions based on fluorescent quantum dots (QD) and carbon black (CB) are presented in detail. The latter creates superhydrophobic surfaces on arbitrary substrates, e.g. chips made from cyclic olefin copolymer (COC, water contact angle = 157.9°), provides good visibility for the visual QC in polymer labs-on-a-chip and increases the burst pressures of the hydrophobic valves. Finally, an application is presented which aims at the on-chip amplification of mRNA based on defined flow control by hydrophobic valves is presented. Here, the optimization based on QC in combination with the Teflon-CB coating improves the burst pressure reproducibility from 14.5% down to 6.1% compared to Teflon-coated valves.

Optical beam guidance in monolithic polymer chips for miniaturized colorimetric assays

For the first time, we present a simple and robust optical concept to enable precise and sensitive read-out of colorimetric assays in flat lab-on-a-chip devices. The optical guidance of the probe beam through an incorporated measurement chamber to the detector is based on the total internal reflection at V-grooves in the polymer chip. This way, the optical path length through the flat measurement chamber and thus the performance of the measurements are massively enhanced compared to direct (perpendicular) beam incidence. This is demonstrated by a chip-based, colorimetric glucose-assay on serum. Outstanding features are an excellent reproducibility (CV= 1.91 %), a competitive lower limit of detection (c/sub min/ = 124 /spl mu/M), and a high degree of linearity (R/sup 2/ = 0.998) within a working range extending over nearly three orders of magnitude.

Design and Fabrication of a Centrifugally Driven Microfluidic Disk for Fully Integrated Metabolic Assays on Whole Blood

For the first time, we present a novel and fully integrated centrifugal microfluidic “ lab-on-a-disk” for rapid metabolic assays in human whole blood. All essential steps comprising blood sampling, metering, plasma extraction and the final optical detection are conducted within t = 150 s in passive structures integrated on one disposable disk. Our technology features a novel plasma extraction structure (V = 500 nL, CV < 5%) without using any hydrophobic microfluidics where the purified plasma (cRBC< 0.11%) is centrifugally separated and subsequently extracted through a capillarily primed extraction channel into the detection chamber. While this capillary extraction requires precisely defined, narrow micro-structures, the reactive mixing and detection is most efficient within larger cavities. The corresponding manufacturing technique of these macro- and micro structures in the range of 30 µ m to 1000 µ m is also presented for the first time: A novel, cost-efficient hybrid prototyping technique of a multiscale epoxy master for subsequent hot embossing of polymer disks.

Pico-Injector for the Discrete Chemical Stimulation of Individual Cells with a High Temporal and Spatial Resolution

We present a new tool (Pico-Injector) for the discrete chemical stimulation of individual cells in their physiological environment. Key features are the precisely controlled release of two individually addressable substances in the lower picoliter (pL) range (V = 9 pL) with a high spatial (< 50 μm) and temporal (< 100 μs) resolution while avoid any diffusion-based leakage of the drugs. This is achieved by a disposable and biocompatible cap that is placed on top of a dispenser generating a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter. For the phase-gap we have proven a long term stability of more than 30 hours against capillary priming and a maximum volume ejection rate of up to 220 nL/s.