Microfluidics: an enabling technology for the life sciences

During the last year we have investigated existing and future markets, products and technologies for microfluidics in the life sciences. Within this paper we present some of the findings and discuss a major trend identified within this project: the development of microfluidic platforms for flexible design of application specific integrated microfluidic systems. We discuss two platforms in detail which are currently under development in our lab: microfluidics on a rotating CD ("Lab-CD") as well as a platform to realized customized "nanoliter & picoliter dispensing systems"

A centrifugo-magnetically actuated gas micropump

This paper describes a novel gas micropump on a centrifugal microfluidic platform. The pump is integrated on a passive and microstructured polymer disk which is sealed with an elastomer lid featuring paramagnetic inlays. The rotational motion of this hybrid disk over a stationary magnet induces a designated sequence of volume displacements of the elastic lid, leading to a net transport of gas. The pumping pressure scales linearly with the frequency, with a maximum observable pressure of 4.1 kPa. The first application of this rotary device is the production of gas-liquid flows by pumping ambient air into a continuous centrifugal flow of liquid. The injected gas volume segments the liquid stream into a series of liquid compartments. Apart from such multi-phase flows, the new pumping technique supplements a generic air-to-liquid sampling method to centrifugal microfluidic platforms

A simple opto-fluidic switch detecting liquid filling in polymer-based microfluidic systems

A novel detection scheme for detection of liquid levels and bubbles in microfluidic systems, using the principle of total internal reflection (TIR) is presented. A laser beam impinges on the side walls of a channel which are inclined at 45deg. In an unfilled channel of such a "V-groove", TIR deflects the beam by 90deg into a simple light detector. Upon the presence of liquid, the refractive index in the channel changes, thus eliminating deflection by TIR. The detection principle is robust, requiring no calibration, and tolerating alignment errors of the laser larger than the width and depth of the microfluidic channels. The machining of the V-groves can seamlessly be integrated into common polymer microfabrication schemes such as injection molding

Alginate micro-bead fabrication on a centrifugal microfluidics platform

We present a novel method for the direct, centrifugally induced fabrication of small alginate beads displaying adjustable diameters between 180 mum and 800 mum by polymer-tube micronozzles. The size distribution features a CV of 7 - 16 % for the main peak. Up to 600 beads per second and channel are issued from the micronozzle through an air gap towards a standard lab tube ("Eppi") attached to the rotor spinning and containing a curing agent. At spinning frequencies between 5 Hz and 28 Hz, the tubes align horizontally under rotation and return to a vertical position as soon as the rotor is at rest. The hardened beads are collected within the tube for further processing or characterization. This method is considered as a low cost technology for micro encapsulation technologies

TMMF dry film resist as masking layer in deep etching of Pyrex-glass for microfluidic chip fabrication

AbstractWe present the application of dry film resist (TMMF) as new masking technology to process glass wafers using standard wet etching. The considered microfluidic chip features patterned metal electrodes for impedance sensing and hydraulic access holes fabricated on a Pyrex wafer. Therefore, deep etching of through holes, while protecting the deposited metal structures on the Pyrex glass wafer, is required. To achieve this, amorphous silicon (a-Si) was used as masking layer on one side and unexposed TMMF dry film resist was used as mask on the other side of the wafer. The a-Si and TMMF are excellent masking layers in deep-wet etching for Pyrex wafers with etch duration more than 1 hour in 49% hydrofluoric (HF) acid

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

Near-wall velocity of suspended particles in microchannel flow

This contribution investigates the characteristic reduction of the particle velocity with respect to the velocity profile of a pure liquid (water) in a pressure driven flow (PDF). It is shown by simulations and experiments that particles are slowed down once their local perturbation "cloud" of the velocity field hits the wall. We show that this effect scales with the ratio of the distance of sphere's surface from the wall, a, and the radius, a, of the sphere, i.e. delta/a

TIR-based dynamic liquid-level and flow-rate sensing and its application on centrifugal microfluidic platforms

For the first time we present a technique for the spatio-temporally resolved localization of liquid-gas interfaces on centrifugal microfluidic platforms based on total internal reflection (TIR) at the channel wall. The simple setup consists of a line laser and a linear image sensor array mounted in a stationary instrument. Apart from identifying the presence of (usually unwanted) gas bubbles, the here described online meniscus detection allows to measure liquid volumes with a high precision of 1.9%. Additionally, flow rates and viscosities (range: 1-10.7 mPa s) can be sensed even during rotation at frequencies up to 30 Hz with a precision of 4.7% and 4.3%, respectively

A one-compartment, direct glucose fuel cell for powering long-term medical implants

We present the operational concept, microfabrication, and electrical performance of an enzyme-less direct glucose fuel cell for harvesting the chemical energy of glucose from body fluids. The spatial concentrations of glucose and oxygen at the electrodes of the one-compartment setup are established by self-organization, governed by the balance of electro-chemical depletion and membrane diffusion. Compared to less stable enzymatic and immunogenic microbial fuel cells, this robust approach excels with an extended life time, the amenability to sterilization and biocompatibility, showing up a clear route towards an autonomous power supply for long-term medical implants without the need of surgical replacement and external refueling. Operating in physiological phosphate buffer solution containing 0.1 wt% glucose and having a geometrical cathode area of 10 cm2, our prototype already delivers 20 µ W peak power over a period of 7 days

Aliquoting structure for centrifugal microfluidics based on a new pneumatic valve

We present a new microvalve that can be monolithically integrated in centrifugally driven lab-on-a-chip systems. In contrast to existing operation principles that use hydrophobic patches, geometrically defined capillary stops or siphons, here we present a pneumatic principle. It needs neither additional local coatings nor expensive micro sized geometries. The valve is controlled by the spinning frequency and can be switched to be open when the centrifugal pressure overcomes the pneumatic pressure inside an unvented reaction cavity. We designed and characterized valves ranging in centrifugal burst pressure from 6700 Pa to 2100 Pa. Based on this valving principle we present a new structure for aliquoting of liquids. We experimentally demonstrated this by splitting 105 muL volumes into 16 aliquots with a volume CV of 3 %