A new pathway for the generation of polymer-based microfluidic devices with tailor-made surface chemistry is described. A simple photochemical process is used to covalently bind polymer molecules to the surfaces of microchannels fabricated by hot embossing. The substrates for the embossing process have the format of a compact disk (CD). CDs from polymethylmethacrylate and polyethylene-co-norbornene were chosen due to their good optical properties. Thin films of polymers containing photoactive benzophenone units were deposited onto the surface of the thus generated devices. These films were subsequently irradiated with UV light leading to the surface-attachment of ultrathin polymer networks. In contrast to their unmodified peers, the obtained, modified microfluidic channels coated with hydrophilic, photoattached layers can be filled in a straightforward manner with water by capillary forces. Channels coated by thin films of poly(ethyloxazoline) show complete resistance to non-specific protein binding. Generation of hydrophobic patches inside the modified microfluidic channels using benzophenone-containing fluoropolymers allowsthegenerationofpassive microfluidic valves to direct fluid motion in these CD-based devices.

We present a novel concept to process human blood on a spinning polymer disk for the determination of the hematocrit level by simple visual inspection. The microfluidic disk which is spun by a macroscopic drive unit features an upstream metering structure and a downstream blind channel where the centrifugally enforced sedimentation of the blood is performed. The bubble-free priming of the blind channel is governed by centrifugally assisted capillary filling along the sloped hydrophilic side-wall and the lid as well as the special shape of the dead end of the two-layer channel. The hematocrit is indicated at the sharp phase boundary between the plasma and the segregated cellular pellet on a disk-imprinted calibrated scale. This way, we conduct the hematocrit determination of human blood within 5 min at a high degree of linearity (R-2=0.999) and at a high accuracy (CV=4.7%) spanning over the physiological to pathological working range. As all processing steps including the priming, the metering to a defined volume as well as the centrifugation are executed automatically during rotation, the concept is successfully demonstrated in a conventional PC-CDROM drive while delivering the same performance (R-2=0.999, CV=4.3%).

In this paper, we present a novel and fully integrated centrifugal microfluidic "lab-on-a-disk" for rapid colorimetric 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, globally hydrophilized structures which obviate the need for intricate local hydrophobic surface patterning. Our technology features a plasma extraction structure (V=500 nL, CV<5%) where the purified plasma (cRBC<0.11%) is centrifugally separated, metered by an overflow and subsequently extracted by a siphon-based principle through a hydrophilic extraction channel into the detection chamber.

Mobile analysis systems allow biological, chemical and medical tests to be performed outside of the established large laboratories. Considerable improvement are made possible by Lab-on-a-Chip systems making use of designated effects on the micron-scale. This allows to perform medical tests in a highly user-friendly, cost-effectively, but still quality fashion, yielding a result within minutes at the point of care. The Bio-Disk project developed a system to determine a multitude of relevant blood parameters within a few minutes from a single drop of blood. The platform possesses a high potential to be applied in point-of-care or emergency diagnostics. Bio-Disk cartridges are currently in the format of a standard compact disc (CD). The processes of the introduced sample is controlled by the interplay of geometrically defined capillary action with the centrifugal field which can dynamically be adjusted by the spinning frequency of the player.

We present novel concepts to process and read out multiplexed, bead-based fluorescence immunoassays. At the start of the read-out process, a statistically arranged monolayer of color-encoded beads is aggregated in a detection chamber. Each bead is first identified by incorporated color tags which are either dyes or luminescing quantum dots (QDs). Subsequently, the reaction-specific fluorescence signal is quantified. The read-out process is accelerated by an in-house-developed image-processing algorithm. The optical read-out device consists of standard components, e.g. a color CCD-camera as detection unit, an LED as light source, optical filters, and a drive to spin the polymer disk. The liquid handling along the complete assay protocol is realized on a centrifugal lab-on-a-disk platform. We successfully demonstrate the performance of this device by the implementation of a hepatitis A and a tetanus assay.

In this paper, we present a novel concept for optical beam-guidance to significantly enhance the sensitivity of colorimetric assays by extending the optical path length through the detection cell which linearly impacts the resulting attenuation of a probe beam according to the law of Beer-Lambert. In our setup, the incident probe beam is deflected by 90∘ into the chip plane at monolithically integrated V-grooves to pass a flat detection cell at its full width (i.e., with a path length of 10 mm) instead of its usually much smaller height. Afterwards, the attenuated beam is redirected by another V-groove towards an external detector. The general beam-guidance concept is demonstrated by a glucose assay on human whole blood on a centrifugal microfluidic “lab-on-a-disk” platform made of COC. We achieve an excellent linearity with a correlation coefficient (R 2) of 0.997 paired with a lower limit of detection (200 μM) and a good reproducibility with a coefficient of variation (CV) of 4.0% over nearly three orders of magnitude. With an accelerated sedimentation of cellular constituents by centrifugal forces, the sample of whole blood can be analyzed in a fully integrated fashion within 210 s. This time-to-result can even be improved by the numerical extrapolation of the saturation value. Additionally, the direct assay on whole blood also shows a negligible correlation with the hematocrit of the blood sample.

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%.

We present a novel concept to determine relevant biochemical markers for applications in the field of emergency diagnostics. Our modular setup comprises a disposable polymer disk which hosts microfluidic structures and optical beam-guidance elements. The beam of a standard laser is guided by total internal reflection (TIR) at V-grooved retro reflectors which are monolithically integrated on a “lab-on-a-disk”. This way, the optical path length through the commonly flat detection cell and thus the sensitivity of colorimetric assays is massively enhanced compared to direct (perpendicular) beam incidence. The reusable analyzer compactly incorporates a standard drive to spin the disk, a dispensing unit, a low-cost laser, and a spectrophotometer serving as flexible detector for different assay formats. The competitive performance of the setup was proven by the rapid and accurate determination of the concentration of hemoglobin (Hb) in human whole blood. Outstanding features are a high degree of linearity (R2=0.993) between the optical signal and the Hb, a good reproducibility of CV=2.9%, and a time-to-result of 100s, only.

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 (c RBC < 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.

We present a concept for optical beam guidance by total internal reflection (TIR) at V-grooves as retro reflectors which are monolithically integrated on a microfluidic "lab-on-a-disk". This way, the optical path length through a measurement chamber and thus the sensitivity of colorimetric assays is massively enhanced compared to direct (perpendicular) beam incidence. With this rugged optical concept, we determine the concentration of hemoglobin (Hb) in human whole blood. Outstanding features are a high degree of linearity (R/sup 2/ = 0.993) between the optical signal and the Hb together with a reproducibility of CV= 2.9 %, and a time-to-result of 100 seconds, only.

This paper presents an optical concept for the read-out of a parallel, bead-based fluorescence immunoassay conducted on a lab-on-a-disk platform. The reusable part of the modular setup comprises a detection unit featuring a single LED as light source, two emission-filters, and a color CCD-camera as standard components together with a spinning drive as actuation unit. The miniaturized lab-on-a-disk is devised as a disposable. In the read-out process of the parallel assay, beads are first identified by the color of incorporated quantum dots (QDs). Next, the reaction-specific fluorescence signal is quantified with FluoSpheres-labeled detection anti-bodies. To enable a fast and automated read-out, suitable algorithms have been implemented in this work. Based on this concept, we successfully demonstrated a Hepatitis-A assay on our disk-based lab-on-a-chip.

This work presents a new experimental setup for image capturing of centrifugally driven flows in disk-based microchannels rotating at high frequencies of up to 150Hz. To still achieve a micron-scale resolution, smearing effects are minimized by a microscope-mounted CCD camera featuring an extremely short minimum exposure time of 100ns, only. The image capture is controlled by a real-time PC board which sends delayed trigger signals to the CCD camera and to a stroboscopic flash upon receiving the zero-crossing signal of the rotating disk. The common delay of the trigger signals is electronically adjusted according to the spinning frequency. This appreciably improves the stability of the captured image sequences. Another computer is equipped with a fast framegrabber PC board to directly acquire the image data from the CCD camera. A maximum spatial resolution ranging between 4.5μm at rest and 10μm at a 150Hz frequency of rotation is achieved. Even at high frequencies of rotation, image smearing does not significantly impair the contrast. Using this experimental setup, the Coriolis-induced patterning of two liquid flows in 300-μm-wide channels rotating at 100Hz is visualized at a spatial resolution better than 10μm.

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.

We present a novel concept for mixing of liquids on centrifugal microfluidic platforms based on the deflection of magnetic beads by stationary permanent magnets. Outstanding features of this batch mode mixer are its high speed of mixing (mixing time of less than 1 s compared to 7 min for mere diffusion), its scalability (volumes between 1 nl and 1 ml can be processed), its simple and modular setup (macroscopic actuation, no 3-D micromachining, no moving microparts except for magnetic beads, possibly disposable disk) and the low spinning frequencies (similar to 10 Hz).

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.