A single channel capillary microviscometer

We have developed a microviscometer analyzing the fluid dynamics in a single channel glass microfluidic chip with a closed end. The device is able to test sample volumes of a few microliters by inserting one drop in the inlet. The fluid enters the channel driven by capillary pressure and an optical sensor registers the motion. The equation that describes the fluid dynamics is function of the channel geometry, atmospheric pressure, fluid viscosity, and capillary pressure. Knowing the first two, the last parameters can be obtained as fitting parameters from the meniscus position as a function of time plot. We have successfully tested Newtonian fluids with different viscosities and capillary pressure.     

A serial sample loading system: interfacing multiwell plates with microfluidic devices

There is an increasing demand for novel high-throughput screening (HTS) technologies in the pharmaceutical and biotechnological industries. The robotic sample-handling techniques currently used in these industries, although fast, are still limited to operating in multiwell plates with the sample volumes per reaction in the microliter regime. Digital microfluidics offers an alternative for reduction in sample volume consumption for HTS but lacks a reliable technique for transporting a large number of samples to the microfluidic device. In this report, we develop a technique for serial delivery of sample arrays to a microfluidic device from multiwell plates, through a single sample inlet. Under this approach, a serial array of sample plugs, separated by an immiscible carrier fluid, is loaded into a capillary and delivered to a microfluidic device. Similar approaches have been attempted in the past, however, either with a slower sample loading device such as a syringe pump or vacuum-based sample loading with limited driving pressure. We demonstrated the application of our positive-pressure-based serial sample loading (SSL) system to load a series of sample plugs into a capillary. The adaptability of the SSL system to generate sample plugs with a variety of volumes in a predictable manner was also demonstrated.     

Controlling capillary-driven surface flow on a paper-based microfluidic channel

This paper describes two methods for controlling capillary-driven liquid flow on microfluidic channels. Unlike flow driven by external forces, capillary-driven flow is dominated by interfacial phenomena and, therefore, is sensitive to the channel geometry and chemical composition (surface energy) along the channel. The first method to control fluid flow is based on altering surface energy along the channel through regulation of UV irradiation time, which enables adjusting the contact angle along the fluid path. The slowing down (delay) of the liquid flow depends on the stripe length and its position in the channel. Using this technique, we generated flow delays spanning from a second to over 3 min. In the second approach, we manipulated the flow velocity by introducing contractions and expansions in the channel. The methods used herein are inexpensive and can be incorporated to the microfluidic channel fabrication step. They are capable of controlling liquid flow with precise time delays without introducing the foreign matter in the fluidic device.     

Vertical liquid transportation through capillary bundle structure using centrifugal force

The use of three-dimensional (3D) microstructures is becoming essential attempt to develop next generations’ microdevices, to integrate many modules and various functions, and enhance the performance of device. In this paper, we present a new concept for lab on a chip using 3D structure and centrifugal pumping for integrated functional fluid systems such as high-throughput screening, and point of care testing systems which has stacked multiple structures with 3D-interconnection. The use of 3D structure brings many benefits for above high throughput systems, such as possibility to integrate various modules enabling to perform total assay operation, from sample preparation for biochemical reaction and their detection on one platform. For this concept, the most important key technology is control of a vertical valving and transportation of liquid between different 2D micro channel networks with different height levels. We demonstrated such vertical liquid transportation in 3D micro channel networks through the high aspect ratio capillary bundle filter by controlling spinning speed of device and centrifugal force as a pumping force, and confirmed capillary bundle could be employed as vertical microvalve for 3D fluidic systems using centrifugal force as a pumping method.     

Microfluidic counterflow centrifugal elutriation system for sedimentation-based cell separation

We present a centrifugal microfluidic system for precise cell/particle sorting using the concept of counterflow centrifugal elutriation (CCE). A conventional CCE system uses a rotor device incorporating a flow-through separation chamber, in which the balance of centrifugal and counterflow drag forces exerted on particles is gradually shifted by changing the flow rate and/or the rotation speed. In the present system, both the centrifugal and the fluid forces are generated through microdevice rotation in order to significantly simplify the setup of the conventional CCE. In addition, the density gradient of the medium is employed to elute particles/cells of different sedimentation velocities stepwise from the separation chamber instead of changing the rotation speed. We successfully separated polymer particles with diameters of 1.0–5.0 μm using a branched loading channel for focusing particles to the center of the separation chamber. We also demonstrated the sorting of blood cells for biological applications. This system may provide a versatile means for cell/particle sorting in a general biological laboratory and function as a unit operation in various centrifugal microfluidic platforms for biochemical experiments and clinical diagnosis.     

Self-priming of liquids in capillary autonomous microfluidic systems

We present a numerical approach to the capillary rise dynamics in microfluidic channels of complex 3D geometries. In order to optimize the delivery of specific biological fluids to target regions in microfluidic capillary autonomous systems (CAS), we analyze self-priming of liquid water into a microfluidic device consisting of a microfluidic channel that feeds a rectangular microfluidic cavity trough an appropriately designed micro-chamber. The target performance criteria in our optimization are (1) fast and complete wetting of the cavity bottom while (2) minimizing the probability of trapping air bubble in the device. The numerical model is based on the lattice Boltzmann method (LBM) and a three-dimensional single-component multiple-phase (SCMP) scheme. By using a parallel implementation of this algorithm, we investigate the physical processes related to the invasion of the liquid–gas interfaces in rectangular cavities at different liquid–solid contact angle and shapes of the transition micro-chamber. The numerical results has successfully captured important qualitative and some key quantitative effects of the liquid–solid contact angle, the roughness of the cavity edges, the depth of the holes and shape of the micro-chambers. Moreover, we present and validate experimentally simple geometrical optimizations of the microfluidic device that ensure the complete filling the microfluidic cavity with liquid. Critical parameters related to the overall priming time of the device are presented as well.     

Measurement of dynamic properties of small volumes of fluid using MEMS

A model based on the response of a micro-rheometer which permits the measurement of the linear viscoelastic properties of small volumes of a fluid is described. The configuration involves a liquid being contained within a capillary bridge between two flat smooth parallel platens that are actuated sinusoidally using a compliant MEMS device. Approximate closed-form equations are derived to analyse the data taking account of both the capillary forces and those arising from viscoelastic flow. The approximate theory is compared to a full numerical simulation of the response of the MEMS rheometer and the validity is discussed.     

Integrated microfluidic viscometer equipped with fluid temperature controller for measurement of viscosity in complex fluids

In the study described herein, a microfluidic viscometer equipped with fluid temperature controller is proposed for measuring the viscosity of complex liquids containing cells or particles. The microfluidic viscometer is composed of a microfluidic device and a fluid temperature controller. The microfluidic device has two inlets, for the introduction of the sample and reference fluids, respectively, and a spacious diverging channel with a large number of identical indicating channels. A fluid temperature controller, which contained a Peltier chip, micro thermocouples, and a feedback controller, is applied for the consistent control of the temperature of the fluids in the microfluidic channels. For accurately identifying fluid viscosity, an effective design criterion is discussed using an enhanced mathematical model for complex fluid networks. The accuracy of the proposed model is sufficiently investigated via numerical simulations as well as experimental measurements. As performance demonstrations, pure liquids [five different concentrations of SDS (Sodium Dodecyl Sulphate)] and complex fluids (four different blood samples) were used to evaluate the performance of the proposed microfluidic viscometer. This investigation indicated that the proposed microfluidic viscometer is capable of accurately and simply measuring both Newtonian and non-Newtonian fluids, even without the need for calibration procedures, and artifacts faced with a conventional viscometer. We therefore conclude that our proposed microfluidic viscometer has considerable potential for the precise and easy measurement of complex fluid viscosity.     

A high-shear, low Reynolds number microfluidic rheometer

We present a microfluidic rheometer that uses in situ pressure sensors to measure the viscosity of liquids at low Reynolds number. Viscosity is measured in a long, straight channel using a PDMS-based microfluidic device that consists of a channel layer and a sensing membrane integrated with an array of piezoresistive pressure sensors via plasma surface treatment. The micro-pressure sensor is fabricated using conductive particles/PDMS composites. The sensing membrane maps pressure differences at various locations within the channel in order to measure the fluid shear stress in situ at a prescribed shear rate to estimate the fluid viscosity. We find that the device is capable to measure the viscosity of both Newtonian and non-Newtonian fluids for shear rates up to 10⁴ s^?1 while keeping the Reynolds number well below 1.     

Mathematical analysis of oxygen transfer through polydimethylsiloxane membrane between double layers of cell culture channel and gas chamber in microfluidic oxygenator

For successful cell culture in microfluidic devices, precise control of the microenvironment, including gas transfer between the cells and the surrounding medium, is exceptionally important. The work is motivated by a polydimethylsiloxane (PDMS) microfluidic oxygenator chip for mammalian cell culture suggesting that the speed of the oxygen transfer may vary depending on the thickness of a PDMS membrane or the height of a fluid channel. In this paper, a model is presented to describe the oxygen transfer dynamics in the PDMS microfluidic oxygenator chip for mammalian cell culture. Theoretical studies were carried out to evaluate the oxygen profile within the multilayer device, consisting of a gas reservoir, a PDMS membrane, a fluid channel containing growth media, and a cell culture layer. The corresponding semi-analytical solution was derived to evaluate dissolved oxygen concentration within the heterogeneous materials, and was found to be in good agreement with the numerical solution. In addition, a separate analytical solution was obtained to investigate the oxygen pressure drop (OPD) along the cell layer due to oxygen uptake of cells, with experimental validation of the OPD model carried out using human umbilical vein endothelial cells cultured in a PDMS microfluidic oxygenator. Within the theoretical framework, the effects of several microfluidic oxygenator design parameters were studied, including cell type and critical device dimensions.     

A novel filtration method integrated on centrifugal microfluidic devices

A method has been developed that integrates filters directly into centrifugal microfluidic devices. This technique is suitable for both rapid prototyping and commercial applications. Commercially available filter paper was sealed into the centrifugal microfluidic device with a simple manual fabrication procedure. The method was validated using soil slurry in water and a variety of filter papers with pore sizes ranging from 0.7 to 11 μm. Filtration times of 4 s to several minutes were obtained for 100 μL samples depending on the type of filter paper and rotation rate utilized. The validity of the method was demonstrated by assessing the amount of light lost due to the scatter or absorption caused by particles in the filtered sample while the device was in motion. Filtration and sedimentation were compared and after 30 min of centrifugation, sedimentation had not removed particles as well as filtration. This technique opens up centrifugal microfluidic devices to a wide range of samples.     

Thin film evaporation in microchannels with interfacial slip

We investigate the role of interfacial slip on evaporation of a thin liquid film in a microfluidic channel. The effective slip mechanism is attributed to the formation of a depleted layer adhering to the substrate–fluid interface, either in a continuum or in a rarefied gas regime, as a consequence of intricate hydrophobic interactions in the narrow confinement. We appeal to the fundamental principles of conservation in relating the evaporation mechanisms with fluid flow and heat transfer over interfacial scales. We obtain semi-analytical solutions of the pertinent governing equations, with coupled heat and mass transfer boundary conditions at the liquid–vapor interface. We observe that a general consequence of interfacial slip is to elongate the liquid film, thereby leading to a film thickening effect. Thicker liquid films, in turn, result in lower heat transfer rates from the wall to liquid film, and consequently lower mass transfer rates from the liquid film to the vapor phase. Nevertheless, the total mass of evaporation (or equivalently, the net heat transfer) turns out to be higher in case of interfacial slip due to the longer film length. We also develop significant physical insights on the implications of the relative thickness of the depleted layer with reference to characteristic length scales of the microfluidic channel on the evaporation process, under combined influences of the capillary pressure, disjoining pressure, and the driving temperature differential for the interfacial transport.     

Liquid bridge instability applied to microfluidics

This paper presents a new way of combining and mixing reagents within one droplet, which may then be used as a microfluidic biochemical reactor. This is made possible by coalescing aqueous droplets on opposing microcapillary tips immersed in density-matched silicone oil. It was found that there are two possible outcomes from a binary capillary-suspended droplet interaction. The droplets may coalesce to form a stable fluid bridge between opposing capillary tips. The droplets may, however, coalesce to form an unstable liquid bridge that quickly ruptures resulting in the two fluid volumes combining into one droplet suspended from a single capillary tip. The stability boundary that determines one outcome or the other was found to be related to a number of variables that describe the equilibrium shape of the liquid bridge interface. Suspending the host droplet from a larger diameter microcapillary dramatically increases the range of volumes that the system can combine by shifting the stability boundary. This ensures the desired effect of pinch-off near the tip of the finer microcapillary thereby dispensing microfluidic samples in one direction.     

Development of a microfluidic design for an automatic lab-on-chip operation

Simple and easy to use are the keys for developing lab-on-chip technology. Here, a new microfluidic circuit has been designed for an automatic lab-on-chip operation (ALOCO) device. This chip used capillary forces for controlled and precise manipulation of liquids, which were loaded in sequence from different flowing directions towards the analysis area. Using the ALOCO design, a non-expert user is able to operate the chip by pipetting liquids into suitable inlet reservoirs. To test this design, microfluidic devices were fabricated using the programmable proximity aperture lithography technique. The operation of the ALOCO chip was characterized from the flow of red-, blue- and un-dyed deionized water. Experimental result indicated that red water, which filled first the analysis area, was substituted entirely with blue water. Controlled sequential flows of these water in the ALOCO device are demonstrated in this paper.     

Magnetically controlled valve for flow manipulation in polymer microfluidic devices

A simple, external in-line valve for use in microfluidic devices constructed of polydimethylsiloxane (PDMS) is described. The actuation of the valve is based on the principle that flexible polymer walls of a liquid channel can be pressed together by the aid of a permanent magnet and a small metal bar. In the presence of a small NdFeB magnet lying below the channel of interest, the metal bar is pulled downward simultaneously pushing the thin layer of PDMS down thereby closing the channel stopping any flow of fluid. The operation of the valve is dependent on the thickness of the PDMS layer, the height of the channel, the gap between the chip and the magnet and the strength of the magnet. The microfluidic channels are completely closed to fluid flows ranging from 0.1 to 1.0 μL/min commonly used in microfluidic applications.     

The manufacturing of packaged capillary action microfluidic systems by means of CO2 laser processing

In this article we demonstrate a simple yet robust rapid prototyping manufacturing technique for the construction of autonomous microfluidic capillary systems by means of CO₂ laser processing. The final packaging of the microfluidic device is demonstrated using thermal lamination bonding and allows for a turnaround time of approximately 30 min to 3 h from activation of the laser system to device use. The low-cost CO₂ laser system is capable of producing repeatable microfluidic structures with minimum feature sizes superior than 100–150 μm over channel depths of more than 100 μm. This system is utilised to create capillary pump and valve designs within poly (methyl methacrylate) (PMMA) substrates. Such components are part of advanced systems that can self initiate and maintain the flow of various volumes of fluids from an input to a collection reservoir, whilst also controlling the progression of the flow through the various demonstrated valve type structures. The resulting systems could prove a very useful alternative to traditional, non-integrated, fluidic actuation and flow control systems found on-chip, which generally require some form of energy input, have limited portable capabilities and require more complex fabrication procedures.     

Behavior of capillary valves in centrifugal microfluidic devices prepared by three-dimensional printing

This paper details the behavior of capillary valves in centrifugal microfluidic devices prepared by three-dimensional (3D), or solid-object, printing. Microfluidic structures containing valve channels with different widths, heights, and radial distances from the center of rotation were studied and compared with extant capillary valve theories. Due to the printing process, the produced valve channels possessed a ridged or “scalloped” pattern. Hence, actual channel widths at the widest and narrowest points of the ridged pattern were determined, and used in comparisons between theoretical and empirical values. In addition, variations in contact angle resulting from the ridged pattern were measured and employed in theoretical calculations. For 1-mm high valve channels, the critical angular frequency (rpm) required to overcome capillary valve pressure was found to be independent of width. However, as the height of the valve channel was reduced, the critical rpm was found to become progressively more width-dependent increasing more rapidly for narrower channels. Both of these observations point to a role for feature sharpness, as well as the geometry of the valve channel opening, in valve behavior. Otherwise, valves followed a predictable trend of increasing critical rpm with decreased valve height and decreased radial distance from the rotation center. Using these results as a guide, then, it is possible to prepare centrifugal microfluidic devices by 3D printing with operability comparable to devices prepared by other microfabrication techniques.     

Integration of microfluidic sample delivery system on silicon nanowire-based biosensor

Silicon nanowire-based (SiNW) biosensors have gained a lot of attention during recent years. However, studies often totally neglect, or only briefly describe, the incorporation of microfluidic channel into the sensor architecture, although it is a crucial step towards a real lab-on-chip device. This paper proposes a process that can be applied to integration of microfluidic sample delivery system onto different SiNW biosensors. The sample delivery system includes a hydrophilic channel that enables the use of capillary action in delivering sample directly onto the sensor array, which leads to reduced sample loss, faster detection process, and frees from the use of external pumps. In addition, the microfluidic channel system protects the fragile SiNWs from mechanical shocks, chemical spatters, and dust. The sample delivery system was fabricated of surface treated polydimethylsiloxane (PDMS), using a four-step approach, as follows: (1) master molds for soft lithography were etched onto Si. (2) PDMS replicas of the molds were fabricated and (3) bonded onto example sensor chips using oxygen plasma. (4) Oxygen plasma treatment also enabled the attachment of polyvinylpyrrolidone (PVP) to the sample channel surfaces to synthesize hydrophilic polymer coating. A contact angle for the PVP treated PDMS was 21 after 17 days, indicating the formation of a long-term hydrophilic PDMS surface. Finally, the example SiNW sensor is modified to allow direct real-time detection of thyroid-stimulating hormone (TSH). The sensor was able to detect as low TSH concentration values as 0.5 mIU/l, which indicates a successfully integrated sample delivery system.     

Thermo-pneumatic pumping in centrifugal microfluidic platforms

The pumping of fluids in microfluidic discs by centrifugal forces has several advantages, however, centrifugal pumping only permits unidirectional fluid flow, restricting the number of processing steps that can be integrated before fluids reach the edge of the disc. As a solution to this critical limitation, we present a novel pumping technique for the centrifugal microfluidic disc platform, termed the thermo-pneumatic pump (TPP), that enables fluids to be transferred the center of a rotating disc by the thermal expansion of air. The TPP is easy to fabricate as it is a structural feature with no moving components and thermal energy is delivered to the pump via peripheral infrared (IR) equipment, enabling pumping while the disc is in rotation. In this report, an analytical model for the operation of the TPP is presented and experimentally validated. We demonstrate that the experimental behavior of the pump agrees well with theory and that flow rates can be controlled by changing how well the pump absorbs IR energy. Overall, the TPP enables for fluids to be stored near the edge of the disc and transferred to the center on demand, offering significant advantages to the microfluidic disc platform in terms of the handling and storage of liquids.     

Acoustically Driven Programmable Microfluidics for Biological and Chemical Applications

In summary, we described a novel and unconventional technique to manipulate smallest amounts of liquid on a chip. Using SAW on a piezoelectric substrate, we are able to actuate individual droplets along predetermined trajectories, or induce acoustically driven internal streaming in the fluid. This internal acoustic streaming can efficiently be used to agitate, mix, and stir very small liquid volumes, where the low Reynold's number usually only allows for diffusive mixing. We described several applications of the SAW driven microfluidics, including a nanomixer for microarray applications, a contactless mixer for MTPs, a programmable microfluidic chip for droplet-based assays, and finally a chip performing high resolution microliter PCR. The technique is equally well suited to actuate or agitate small amounts of liquids either in closed volumes or in an open, droplet-based geometry. Each of the approaches has its clear advantages, but also disadvantages. Droplet-based fluidics is certainly well suited to handle smallest amounts of fluids without the risk of cross contamination etc. High temperature processes, however, require additional means like covering the droplet with an oil film. SAW pumping, mixing, and stirring on closed volumes is advantageous over many other pumping schemes as the pumps are easily incorporated into most of the existing microfluidic device or lab-on-a-chip. The combination of the SAW actuated droplet-based fluid handling and SAW driven fluidics in closed volumes opens a wide field of many different applications, a few of which I had the pleasure to present in this article. Many more applications, and many more visualizations of the technology described above can be looked up on Advalytix' website http://www.Advalytix.de.