Droplet mixer based on siphon-induced flow discretization and phase shifting

We present a novel mixing principle for centrifugal microfluidic platforms. Siphon structures are designed to disrupt continuous flows in a controlled manner into a sequence of discrete droplets, displaying individual volumes as low as 60 nL. When discrete volumes of different liquids are alternately issued into a common reservoir, a striation pattern of alternating liquid layers is obtained. In this manner diffusion distances are drastically decreased and a fast and homogeneous mixing is achieved. Efficient mixing is demonstrated for a range of liquid combinations of varying fluid properties such as aqueous inks or saline solutions and human plasma. Volumes of 5 muL have been mixed in less than 20 s to a high mixing quality. One-step dilutions of plasma in a standard phosphate buffer solution up to 1:5 are also demonstrated

Concentration of white blood cells from whole blood by dual centrifugo-pneumatic siphoning with density gradient medium

Due to the pervasiveness of HIV infections in developing countries there exists a need for a low-cost, user-friendly point-of-care device which can be used to monitor the concentration of T-lymphocytes in the patient’s blood expressing the CD4+ epitope. As a first step towards developing a microfluidic “lab-on-a-disc” platform with this aim we present the concentration of white blood cells from whole blood using a density medium in conjunction with centrifugo-pneumatic siphon valves [1]. Two such valves are actuated simultaneously, removing the bulk of plasma through the upper valve and the bulk of WBCs through the lower valve while leaving the vast majority of red blood cells in the centrifugal chamber

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

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

Monolithic centrifugal microfluidic platform for bacteria capture and concentration, lysis, nucleic-acid amplification, and real-time detection

We report the design, fabrication, and characterization of a polymer centrifugal microfluidic system for the specific detection of bacterial pathogens. This single-cartridge platform integrates bacteria capture and concentration, supernatant solution removal, lysis, and nucleic-acid sequence-based amplification (NASBA) in a single unit. The unit is fabricated using multilayer lamination and consists of five different polymer layers. Bacteria capture and concentration are accomplished by sedimentation in five minutes. Centrifugation forces also drive the subsequent steps. A wax valve is integrated in the cartridge to enable high-speed centrifugation. Oil is used to prevent evaporation during reactions requiring thermal cycling. Device functionality was demonstrated by real-time detection of E. coli from a 200-muL sample

Lumped-Element Modeling for Rapid Design and Simulation of Digital Centrifugal Microfluidic Systems

Since the 1990s, centrifugal microfluidic platforms have evolved into a mature technology for the automation of bioanalytical assays in decentralized settings. These “Lab-on-a-Disc” (LoaD) systems have already implemented a range of laboratory unit operations (LUOs) such as sample loading, liquid transport, metering, aliquoting, routing, mixing, and washing. By assembling these LUOs in highly functional microfluidic networks, including sample preparation and detection, a sizable portfolio of common test formats such as general chemistry, immunoassays/ protein analysis, nucleic acid testing, and cell counting has been established. The availability of these bioanalytical assay types enables a broad range of applications in fields such as life-science research, biomedical point-of-care testing and veterinary diagnostics, as well as agrifood, environmental, infrastructural, and industrial monitoring

Liquid recirculation in microfluidic channels by the interplay of capillary and centrifugal forces

We demonstrate a technique to recirculate liquids in a microfluidic device, maintaining a thin fluid layer such that typical diffusion times for analytes to reach the device surface are < 1 min. Fluids can be recirculated at least 1000 times across the same surface region, with no change other than slight evaporation, by alternating the predominance of centrifugal and capillary forces. Mounted on a rotational platform, the device consists of two hydrophilic layers separated by a thin pressure-sensitive adhesive (PSA) layer that defines the microfluidic structure. We demonstrate rapid, effective fluid mixing with this device

Auto-actuated sequential relelase valves for lab-on-a-disc systems

In microfluidic biomedical systems valving is often of critical importance for process control. In centrifugal microfluidics valves are typically actuated through changing the centrifugal force seen by the working liquid. Here we present for the first time a new valving structure (based on dissolvable films) where the entry of liquid into a chamber on the disc can trigger the release of liquid from a chamber located elsewhere on the disc. These valves can be configured such that multiple valves can be released in a sequential manner independent of external inputs

Portable Lab-on-a-Disc system integrating photo-switchable micro-valves for in-situ aquatic environmental monitoring

This work describes the first use of a portable centrifugal microfluidic analysis system (CMAS) for on-site lab-on-a-disc water quality monitoring. The centrifugal microfluidic platform designed for the detection of nitrite in multiple water samples incorporates photo-switchable microvalves, which are easily controlled using white light irradiation. Calibration of the CMAS system resulted in a linear response that obeys the Beer-Lambert Law. Excellent correlation of results between the CMAS device and a standard UV-Vis spectrophotometer were obtained

Reciprocating, buoyancy-driven radial pumping on centrifugal microfluidic platforms

Centrifugal microfluidic systems bear great potential for applications where ruggedness, portability, ease-of-use, and cost efficiency are critical. However, due to the unidirectional nature of the centrifugal pumping force, the number of sequential process steps which can be integrated on these “Lab-on-a-Disc” (LoaD) devices is limited by their finite radial extension. To significantly widen this bottleneck and thus expand the scope of applications that can be ported on these LoaD platforms, various groups have developed a range of centripetal pumping mechanisms. Here, we present two advancements over our previous efforts in this area by combining buoyancy-based pumping with dissolvable film (DF) valves. First, we present a buoyancy-driven, reciprocating flow of a dense liquid initially located an upper reservoir and a sample in a peripheral reservoir. Secondly, we combine buoyancy-driven centripetal pumping with sample discretization and metering to fully integrate and automate a liquid handling protocol towards implementing a multi-parameter bioassay on a disc