Microfluidic Apps for off-the-shelf instruments

Within the last decade a huge increase in research activity in microfluidics could be observed. However, despite several commercial success stories, microfluidic chips are still not sold in high numbers in mass markets so far. Here we promote a new concept that could be an alternative approach to commercialization: designing microfluidic chips for existing off-the-shelf instruments. Such "Microfluidic Apps" could significantly lower market entry barriers and provide many advantages: developers of microfluidic chips make use of existing equipment or platforms and do not have to develop instruments from scratch; end-users can profit from microfluidics without the need to invest in new equipment; instrument manufacturers benefit from an expanded customer base due to the new applications that can be implemented in their instruments. Microfluidic Apps could be considered as low-cost disposables which can easily be distributed globally via web-shops. Therefore they could be a door-opener for high-volume mass markets.     

Fully vectorial eigenmode calculation of dielectric waveguides using a Rayleigh--Ritz method with rational basis functions

A fully vectorial Rayleigh--Ritz method for the eigenmode calculation of dielectric waveguides is presented. It uses the four transversal field components and takes rational functions as an orthonormal basis. This formalism is especially useful near the cutoff frequency and has been applied for the investigation of the polarization properties of the output waveguides in integrated spot-size transformers. This revised version was published online in November 2006 with corrections to the Cover Date.     

Aggregation of bead-monolayers in flat microfluidic chambers - simulation by the model of porous media

In this paper, we for the first time simulate the process of hydrodynamic bead aggregation in a flat micro-fluidic chamber by a porous-media model in an iterative routine. This allows us to optimize the chamber design of our recently developed experimental method to form periodical monolayers from the flow of bead suspension. Periodical monolayers are advantageous for parallel assay formats since they enhance the mechanical rigidity of the aggregated pattern. This is important to avoid a spatial rearrangement along various steps of a read-out procedure which would impair the correlation between measurements. Furthermore, the monolayer formation guarantees the individual optical accessibility of all probe beads. By modelling the monolayers with porous media, we can drastically reduce the degrees of freedom in a two-phase, multi-particle problem. This way, we are able to compute stationary hydrodynamic flow patterns in the chamber. In order to simulate the complete filling process from these stationary solutions, we developed an iterative master routine which takes the transient aggregation pattern as the initial condition, then evaluates the placement of the newly introduced beads, and finally converts the points of aggregation into porous media.     

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%.     

Centrifugal extraction of plasma from whole blood on a rotating disk

We present a centrifugal process for the extraction of plasma from sediment by a decanting structure, terminating with metered plasma which is readily available for subsequent on-disk processing. Our technique supplies 2 microl plasma from 5 microl of whole blood at moderate spinning frequencies of 40 Hz within 20 s, only. The residual cell concentration in the purified plasma amounts to less than 0.11%, independent of the frequency of rotation. A capillary duct connects the extracted plasma to subsequent on-disk processing units.     

Frequency-dependent transversal flow control in centrifugal microfluidics

This work presents a novel flow switch for centrifugal microfluidic platforms which is solely controlled by the Coriolis pseudo force. This Coriolis switch consists of an inverse Y-structure with one common upstream channel and two symmetric outlets on a rotating disk. Above a certain threshold frequency, the Coriolis force becomes dominant that the entire flow is diverted into one of the outlets which is selected by the direction of rotation. The threshold frequency has been measured to be 350 rad s(-1)(approximately 55.7 Hz) for a channel width of 360 microm and a depth of 125 microm. The results are supported by extensive CFD simulations.     

Multiplex genotyping of KRAS point mutations in tumor cell DNA by allele-specific real-time PCR on a centrifugal microfluidic disk segment

Point Mutations on the Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified as an important predictive biomarker for response to cancer therapy targeting the epidermal growth factor receptor. KRAS mutations are prevalent in up to 40 % of all colorectal carcinomas, and routinely conducted KRAS genotyping is becoming mandatory to predict therapy success and to reduce therapy costs. We report a low-cost, disposable and ready-to-use centrifugal microfluidic cartridge (termed GeneSlice) containing preloaded primers and probes. The GeneSlice cartridge enables the parallel detection of the seven most relevant KRAS point mutations by allele-specific real-time PCR. It represents a cost effective alternative to dideoxy-sequencing with a faster time-to-result (~ 2 h versus up to 20 h in case of dd-sequencing). Microfluidic processing of the GeneSlice along with allele-specific amplification and real-time detection are conducted in a slightly modified, commercially available PCR thermocycler. Intra-chip standard deviation of C_q values on the GeneSlices is negligible (GeneSlice 1: C_q,std.dev. = 0.13; GeneSlice 2: C_q,std.dev?=?0.26). In 23 of 24 experiments, the data for genotyping 6 cancer cell lines (n?=?4 per cell line) agreed with dd-sequencing. Additionally, DNA derived from microdissected formalin-fixed and paraffin embedded colorectal carcinomas of two cases was genotyped correctly and reproducibly (n?=?3 per patient; one GeneSlice excluded from evaluation). The GeneSlice therefore clearly demonstrated the potential to become a valuable tool for routine diagnostics of KRAS mutations by reducing costs and hands-on time. Figure

Photograph of a centrifugal microfluidic cartridge “GeneSlice” for multiplex genotyping of KRAS point mutations from tumor cell DNA by allele-specific real-time PCR. Information about the mutation status is required to predict success of state-of-the-art cancer therapy with antibodies     

StarTube: a tube with reduced contact line for minimized gas bubble resistance

In this work we introduce a novel tubing design for multiphase flow that minimizes gas bubble resistance. The design termed "StarTube" has a lamella-like wall structure and was developed to prevent clogging by gas bubbles. This is performed by forcing gas bubbles into the center of the tube by capillary forces, allowing liquid to bypass in the outer grooves. It was found that the mobility of gas bubbles in such a tube is increased more than 1 order of magnitude. The reason is that the contact line perpendicular to the direction of flow is minimized, reducing resistant effects related to the contact line-in particular, contact angle hysteresis.