Micro & Nanotech : Microfluidics

Micro & Nanotech Portfolios


Streamlined Design for Transferring Analytes

The researchers have now improved their design and developed a microfluidic device that directly integrates with tubes, strip tubes and well plates. In this way a sample can be directly transferred from the device to downstream analysis instruments.

The device comprises a strip of wells that hold various volumes of output fluid. Following sample isolation via the researchers’ previously developed SLIDE technique, the strip containing the sample and output buffer is removed from the SLIDE and applied to a set of strip tubes in the same way that conventional covers would be applied.

Then, by flicking or centrifuging the tubes, the sample is transferred from the cap to the tube. At this point the sample is ready for PCR or other downstream analysis.

Circulating Tumor Cell Assay Using Simple Blood Draw

The researchers now have developed the first fully integrated CTC assay that could eliminate the need for painful biopsies. The device leverages verIFAST technology to capture, purify and molecularly analyze CTCs from a single blood sample.

The sample is deposited in a first well and then magnetically drawn through a second well containing an isolation buffer like oil or wax. The increasingly purified cells are drawn into a final well for extraction or further treatment.

The device includes new technical features and is combined with downstream techniques for staining rare cells like CTCs.

Device Uses Air Gap for Easier Fraction Isolation

UW–Madison researchers have developed a new device for isolating desired fractions from a biological sample. The device is made of two plates separated by a gap. The first plate has droplets of bound sample/PMPs positioned on the surface. A second plate containing another reagent is positioned below. A magnet pulls the PMP/sample from the first plate, through the air gap, onto the second plate.

Microwell Moat Prevents Spillover

UW–Madison researchers have developed a new microwell design for use with conventional micropipetting equipment (e.g., a hand-held micropipette or automated pipetting robot). Similar to other microwell designs, the flat device is checkered with nanoliter microwells. However, in the new design, groups of microwells are ringed by deeper moat-like channels that isolate the groups and prevent any spillover when a fluid droplet, e.g., a reagent or cell suspension, is deposited. The moat also keeps fluid from being ‘squished’ and spread out when a when a lid is applied to seal each microwell, avoiding cross-contamination of each experimental condition.

The design enables multiple different reagents/experimental conditions to be tested on the same device using standard pipetting operations. Together, the new features enable easier, more robust, quantitative and massively parallelized single-cell assays for a range of endpoints that can interface with standard pipette equipment.

Low-Waste and Contamination Device for Isolating Cells from a Biological Sample

UW–Madison researchers have developed an improved microfluidic device for isolating a desired fraction without the sample loss or contamination associated with prior designs.

The device features multiple wells through which a magnet (positioned perpendicularly to gravity) is drawn, attracting the fraction from one well to the next while undesired material settles to the bottom. For this to occur the biological sample first is combined with a magnetically attractive reagent that binds to the targeted fraction and forms a solid-phase substrate.

The sample is deposited in the first well and then magnetically drawn through a second well containing an isolation buffer like oil or wax. The increasingly purified cells are drawn into a final well for extraction or further treatment. Surface tension prevents fluid from spilling between wells.

Handheld Cell Maintenance and Assay Device with Functional Microfluidic Lid

UW–Madison researchers have developed a new design for the handling, freezing, thawing and subsequent study of microliter volumes of cell suspensions. Requiring no additional equipment and adaptable to a wide range of conditions, the device is inexpensive to manufacture and preserves the integrity of cells for research.

The platform employs a functionalized lid, enclosed by a microporous membrane and comprising multiple reservoirs into which cell suspensions are loaded. The addition of cryopreservation fluid permits storage. Another flexible membrane encloses the lid’s bottom side and contains a pinhole. Protective tape seals the reservoirs for shipping and containment.

An assay can be performed readily by peeling away the tape on the top side and placing the device in a thawing bath that removes the preservation fluid via dialysis. The tape on the underside then is taken off and pressure on the pinhole membrane dispenses the fluid into another microfluidic platform containing the specific test components.

Snap-On Microfluidic Lid for Handheld Diagnostics and Chemical Tests

UW–Madison researchers have developed a microfluidic design and method that supports rapid and simplified handheld diagnostics and assays.

The device is formed in two separate sections— a base and a functionalized lid—that can be snapped together. The base has channels running between two ports. The lid, which is disposable and holds a well prepackaged with selected liquids like a drug or chemical, has a piercing mechanism. When pressed to the base, the membrane covering the well is perforated and the substance induced to flow down into the base, through its channels and back up into the lid’s absorption pad.

The functionalized lid can not only pump, but also can be designed to apply a chemical gradient using wells filled with hydrogel and reagents that diffuse into the channels.

Fast, Flexible Platform for Handheld Microfluidic Cell Assays

UW–Madison researchers have developed a new microfluidic device design, KOALA, which can perform assays in five-minute steps without reagent waste or time-consuming preparation.

The chip comprises a disengaging lid and base. The lid is networked by channels with protruding inputs while the base features multiple fluid wells and an absorbent pad. When the two components are pressed together, fluid from the wells is drawn into the channel by the pad’s capillary action.

Additional functionalities, like creating gradients with a diffusing source, also are achievable given the design’s passive fluid contact at the channel extremities. Packaged with the reagents and cells required of the assay and enabling encapsulation and freezing, KOALA is an eminently accessible and flexible assay tool.

Achieving Precision Laminar Flow for Biological Microfluidics

UW–Madison researchers have developed a microfluidic method and device to provide controlled laminar flow patterning of samples in one or multiple channels with asynchronous pumping.

The network comprises multiple fluid loading ports leading to respective buffering reservoirs. Flow synchronization is achieved by linking the reservoirs to a common pool acting as a capacitor that, when charged by the presence of a sample, triggers flow. In this way fluid can be added asynchronously through any input port without varying the relative flow rates through the network, converging in the cell culture channel where patterning occurs.

Varying the resistances of the separate branches serves to control the ratio by which the shared culture channel is divided into the multiple flows. This design therefore eliminates the need for synchronized pipetting by utilizing passive components for controlled, reproducible laminar patterning.

More Efficient Method of Purifying a Biological Sample

UW–Madison researchers have developed a simpler, more efficient method for extracting and purifying a fraction from a biological sample. The method involves capturing an analyte onto a solid phase substrate and then using an organic phase to exclude any aqueous solution, resulting in removal of contaminants and isolation of the analyte of interest.

Improved Infrared-Responsive Hydrogel for Use in Microfluidics and Optics

UW–Madison researchers have developed an improved infrared-responsive hydrogel by incorporating graphene oxide flakes into a thermo-responsive hydrogel polymer. These composite hydrogels have an intrinsically higher surface area and absorbance band than conventional metal nanoparticles, resulting in a larger volumetric change in response to infrared light. The researchers also have provided a microfluidic device and a lens structure that incorporate these composite hydrogels as actuators. Both devices can be operated by heating the composite hydrogel in its swollen state to a temperature sufficient enough to shrink its volume. The hydrogel can be restored to its original volume by allowing it to cool and re-swell. In the microfluidic device volume reduction of the hydrogel allows fluid to flow through a channel and in the lens structure volume change relates to a change in focal length. 

Improved Self-Loading Microfluidic Device for Determining Effective Antibiotic Dose and Other Chemical and Biological Assays

UW–Madison researchers have developed a portable, self-loading microfluidic device and method for determining therapeutically effective amounts of agents, MICs and toxicity levels. It can be used to identify bacterial strains and for performing chemical and biological assays. The device comprises a porous organic polymer, a reaction well, an inlet port, a vacuum well, a main channel and a side channel. 

Device for Efficiently Extracting a Fraction Containing Nucleic Acids or Other Desired Material from a Biological Sample

UW–Madison researchers have developed a device and method for extracting and purifying a desired fraction from cultured cells, tissue samples and other biological materials. A biological sample, including both non-desired material and a fraction-bound solid phase substrate, is added to an input zone. The input zone is adjacent to a separation zone that includes an isolation buffer. A force moves the fraction-bound solid phase substrate from the input zone, through the separation zone and into an output zone, leaving the non-desired material behind. The improved purification method is simple, more efficient and produces a higher throughput than prior devices and methods. The device may be configured to allow for quantification of the fraction in the biological sample via labeling of the fraction-bound solid phase substrate.

Method for Isolating Weakly Interacting Molecules from a Fluidic Sample

UW–Madison researchers have developed a method for isolating weakly interacting molecules from a fluidic sample using an immiscible phase filtration technique. A mixture is formed using a fluidic sample and a solid phase substrate including at least one immobilized molecule. The mixture is incubated under conditions that allow the immobilized molecule to interact with a target molecule in the fluidic sample to form a solid phase, substrate-immobilized molecule-target molecule complex. The complex is immediately transferred into an immiscible phase by applying an external force to the solid phase substrate.

Immiscible phase filtration allows for the isolation and identification of weakly interacting molecules from the fluidic sample that were previously unidentifiable using traditional methods, as the analyte is isolated very quickly when the solid phase enters the immiscible phase. The method also provides the capability of providing a “snapshot” of the molecular interactions at equilibrium, which is not possible in traditional methods requiring multiple washes. 

Microfluidic Device for Capturing and Analyzing Rare Cells, Including Circulating Tumor Cells

UW-Madison researchers have developed a microfluidic device for concentrating rare cells.  The velocity of flow through the device is manipulated such that particles in suspension, such as cells, are carried to and deposited in a particular location within the device.  The flow in the region where the cells are deposited is slow, so the cells remain in the collection area without any modifications to the surfaces of the device or cells while the fluid that carried them is routed out of the device.  Because particles in suspension enter the collection region but do not leave, many particles may be captured from a relatively dilute suspension.  The cells then can be cultured, stained and imaged for analysis without being removed from the collection area, creating a gentle and efficient way to implement extensive washing and treatment protocols.

Microfluidic Device for Rapid Nucleic Acid Isolation and Purification

UW-Madison researchers have developed a microfluidic device and method for rapidly extracting and purifying nucleic acids from biological materials. The device includes an input zone for receiving the biological sample, a phase-gate zone for holding an isolation buffer and an output zone for receiving a reagent. The isolation buffer consists of oil that acts as a phase-gate and prevents unwanted material from passing through to the output well. The device employs an isolation mechanism using paramagnetic particles (PMPs), which preferentially bind the nucleic acids, and a lysis buffer, which inhibits the polymerase chain reaction until the nucleic acids have been isolated.

The isolation method proceeds through three main steps. First, the lysis buffer and PMPs are added to the biologic sample in the input well. Then, a magnetic field is used to draw the bound nucleic acid/PMPs through the phase-gate and into the output well, a process that lasts around 15 seconds. This simple phase-gate step replaces the multiple washes required in current methods. Finally, the nucleic acid/PMP reagent is collected for processing via polymerase chain reactions.

The device and method are configured to maximize isolation and purification of nucleic acids while maintaining compatibility with existing multiwell plates and liquid-handling robotic systems. Isolation and purification using this invention can be accomplished in approximately five minutes, including separation, device loading and sample collection. This provides a vast improvement over current kits, which require multiple washing steps and 15 to 45 minutes for purification.

Microfluidic Systems and Methods Applicable to In Vitro Fertilization

UW-Madison researchers have developed a microfluidic device and method that are applicable to in vitro fertilization techniques. The device comprises a substrate with a plurality of microchannels placed in the substrate so that each microchannel includes an inlet at one end to receive a cell and an outlet at the opposite end. Each microchannel also includes a restriction near the outlet to allow the cell to be contained as fluid passes through the channel. At least two microchannels make up an inlet on the substrate, which aligns with a fluid-handling device. The device may be constructed using microfabrication techniques such as injection molding, and may include an automatic top-off system using surface tension-based valve. This inexpensive top-off system reduces inaccurate liquid handling in the microfluidic system, which can lead to contamination of the sample.

The invention provides a flexible platform that allows microscale wells to be sized to accommodate a certain species’ cell size, as well as a fabricated insert to allow the specially sized wells to be included in the system. The system may be configured as a ready-to-use culture system tailored for particular applications, allowing improved embryo growth through optimized cell-to-cell communication. An open-closed-open-closed-open (OCOCO) system may be used for efficient cell culture and convenient sample access, which improves yield by eliminating damage to the sample due to over-handling.

Coupling Microfluidic Devices Yields Physiologically Relevant Micro-Environment for Cellular Assays

UW-Madison researchers have developed an improved device to create a controllable, physiologically relevant micro-environment for studying cellular interactions and pathways. This device provides a means for coupling two discrete microfluidic channels using only fluid contact. Two microchannels, each having one inlet and one outlet, can be coupled by combining fluid droplets on the outlet port and inlet port of the respective microchannel. This fluid contact method allows channels with two isolated environments to initiate the transfer of signaling molecules by means of diffusion or flow, thus allowing controllable physiological communication between cells. Cells can be exposed to a variety of cellular signals without cell contamination by simply breaking fluid contact with the current microchannel and forming a new fluidic coupling with a new microchannel. This new approach can be particularly useful in the co-culture of cells, where cell contamination can be prevalent and result in skewed data.

The controllable micro-environment implemented by this device also provides improved parameters for cellular assays and is well suited for high throughput screening. The reduction of culture dimensions in this microfluidic system results in a more physiologically relevant cellular micro-environment due to certain physical phenomena and interactions that become more dominant. The scale of microfluidic systems offer more precise control over parameters that affect the cellular micro-environment, including fluid shear stress, diffusion of soluble factors and patterning of cells and extracellular matrix (ECM). These parameters can influence cell development and signaling pathways. For example, shear forces can modulate stem cell differentiation pathways and/or apoptotic activity.

In addition, the fluid reduction that results from using a microscale, rather than a macroscale, culture system allows minimal use of expensive reagents. Less reagent use also increases the repeatability and reliability of assays and reduces the amount of time necessary to move cells and reagents in and out of channels.

Population-Averaged Method to Quantify Cell Motility and Migration

UW-Madison researchers have developed an alternative, microtechnology-based method for conducting cell mobility assays. This technique combines microfluidic gradient generation with micro-patterning to simplify the extraction of important migratory information. Rather than tracking individual cells, it uses parameters from the cell population as a whole.

A population of cells is labeled (e.g., with fluorescent dye) and patterned within a microchannel network so the cells are uniformly dispersed along the channel in the form of a generally rectangular strip. A predetermined medium that includes a migration- or motility-promoting signal is patterned along one sidewall of the channel. Then a first image of the population is obtained. After a predetermined time period, a second image is obtained and compared to the first. Simple mathematical processing of the images yields quantitative measurements that can be used to calculate the average directional migration and motility of the cell population.

Robust, Piezoelectrically Actuated High Flow Range Microvalve for Liquid/Gas

UW-Madison researchers have developed a high flow range microvalve that uses a piezoelectric actuator and nesting valve elements to control the flow of a liquid or gas.  In this invention, electronically controlled piezoelectric actuators can cause a silicon micro-machined wafer to flex, and to press onto a complementary glass substrate, applying a very high force.  This creates a valve-closing seal with electronic control that withstands high pressure.  Large flow modulation is achieved by correctly engineering the perimeter of the valve seat. 

Improved Method of Pumping Fluid through a Microfluidic Device

UW-Madison researchers now have improved their passive pumping method. Like the previous method, this system is simple and inexpensive, requiring little additional equipment. Unlike the original microfluidic system, the improved version does not require an output drop. Instead, multiple input pumping drops are used.

In the original device, one of the ports had multiple pores, allowing a greater target area for robotic fluid systems. In the new design, a star-shaped entrance to the microchannel replaces the multiple pores, creating a more uniform fluid flow profile. In addition, the input port itself, rather than just the input droplet, is smaller in this new design, and a tapered port is used to ensure constant contact angle while the droplet shrinks or expands. This change ensures that driving pressure, which is related to contact angle, remains constant.

Geometry and patterning changes in the improved system also provide more versatile port-to-port interactions, including the manipulation of droplet movement to another channel. For example, fluid resistance in the first channel could be designed to create a timing mechanism for autonomous fluid replacement, such as biological waste removal, in a second channel.

System for High-Throughput Analysis of Individual DNA Molecules

UW–Madison researchers have developed improved methods of using channels for tagging, characterizing and sorting individual double-stranded DNA molecules while maintaining the integrity of the biomolecules. In these methods, a single strand of the molecule is broken, or “nicked.” Because the molecule is not cleaved, the nicking process can occur before the DNA is immobilized in a channel. Fluorescently labeled, sequence-specific nucleotides also can be added at specific sites before the DNA is introduced into the channel.

Additionally, nicked DNA molecules can be kept in a low ionic strength buffer to increase their stiffness. This increased stiffness makes it possible for the molecules to remain properly aligned in channels whose height is nanometer scale but whose width is micrometer scale. Using the larger channels simplifies DNA loading, the introduction of reagents and channel construction, reducing costs and making disposable channels practical.

After a nucleic acid molecule is optically analyzed and characterized in a channel, it can be captured, for example by electrostatic attraction, and collected at a defined point in the array. Then the molecule can be released and conveyed for subsequent analysis, such as sequencing.

Device for Improved Cell Staining and Imaging

A UW-Madison researcher has developed a multichannel microfluidic device that increases the efficiency of sample preparation for cell imaging. The microfluidic device includes a cartridge with a patterned inlet port to contain reagent droplets and avoid cross-channel contamination. The lower surface of the cartridge includes several recesses that define channels for containing cells. Different reagents can be added to each channel. The upper surface of a cover slip is placed against the lower surface of the cartridge, and the cartridge is mechanically clamped to the cover slip to ensure no leakage during an assay. After staining is complete, the cover slip can be removed and traditionally mounted to a glass slide for standard imaging protocols.

Methods of Finding, Selecting and Studying Cells in Heterogeneous Co-Cultures

UW-Madison researchers have developed a method of co-culturing heterogeneous primary cells. The cells are cultured in a very small, convection-free space, such as a microchannel, so they behave more as they would in vivo. Because there is no fluid flow, all movement of components in the environment is by diffusion. The culture contains at least one growth-promoting cell and at least one cell capable of proliferating.

Variable-Focus Lens Assembly

UW-Madison researchers have developed an alternative means of making microlenses with adjustable focal lengths. In this method, many fluids may be used for the lens. Responsive hydrogel structures create the tube in which the lens fluid sits. Alternatively, the hydrogel can be coupled to a transparent thin film that will act as the lens. When an environmental parameter, such as temperature or pH, changes, it causes the hydrogel to swell or contract. This in turn causes a change in the focal length of the lens.

Self-Regulating Microsystem that Integrates Silicon- and Polymer-Based MEMS Platforms

UW-Madison researchers have developed an approach to fabricating microsystems that leverages the strengths of both silicon- and polymer-based MEMS platforms. Specifically, they have constructed and tested a self-regulating, temperature-controlled micromixer for creating flow within microchannels.

As in other MEMS, an externally-applied rotating magnetic field drives the mixer’s rotation. But unlike traditional MEMS, which employ standard actuators, the micromixer is turned off and on by using temperature-sensitive hydrogel polymers. 

When the fluid temperature inside a MEMS device rises above a certain temperature, a temperature-sensitive hydrogel ring surrounding the mixer’s axel contracts, freeing the mixer to rotate under control of the magnetic field and pump fluid through the device to cool it. When the temperature cools sufficiently, the hydrogel ring expands and halts the mixer’s rotation.

Microfluidic System for High Throughput Screening

UW-Madison researchers have developed a microtiter plate that uses a simple and inexpensive microfluidics channel system in place of wells for standard high throughput screening using commercially available liquid-handling robots. This technology uses a passive pumping system that eliminates the need for external pumping equipment.

Each microtiter plate includes several microchannels with openings on either end. The input end of each channel consists of a port with multiple pores for receiving drops of fluid. After a liquid-dispensing instrument deposits a drop in the port, the passive pumping system draws it into the channel. To pump liquid through the system, each microchannel is filled with fluid, and a pressure gradient is generated so that fluid flows through the channel toward the output. Assays involving channel networks with multiple ports have also been demonstrated using this system, suggesting that it facilitates high throughput execution of many novel microfluidic cell-based assays as well.

Microfluidics Platform and Method That Mimic the Cellular Environment

UW-Madison researchers have developed a microfluidics-based platform for mimicking the environment within a cell. This model environment is simpler than a cell, yet captures the basic characteristics of the cellular nano-environment, including charge, crowding, water content and structure. It has many advantages over current systems, including the fact it uses much less protein, can detect weaker interactions and requires less time for experiments.

The platform includes a microfluidic device that contains a chamber. At least one hydrogel post is positioned within the chamber. Each post may contain a different density of polymers or a different cross-linker to simulate various crowding or caging effects. A solution containing proteins of interest is introduced into the chamber and the proteins diffuse into the hydrogel posts. The interactions between the proteins are then observed inside the posts.

Microfluidic Device for High Resolution, In Vitro Monitoring of Neuronal Tissue

UW-Madison researchers have developed an in vitro device for examining and testing a slice of brain tissue, which delivers precise amounts of chemical stimuli to neurons with a high degree of spatial and temporal resolution. The device combines the localized drug delivery capability of microfluidics with multi-channel neural recordings.

The device includes a chamber and microfluidic channels that communicate with the chamber. A support structure within the chamber holds the slice of brain tissue and includes an array of electrodes that engages the slice, allowing for multi-channel electrical recording and stimulation of the slice at each of the electrode sites within the microfluidic channels. The microfluidic channels allow many parallel, but independent, laminar fluid streams to flow across the surface of the brain slice. Special valves enable a highly focused stream of chemicals to flow across the slice at any desired location while being pulsed with high temporal resolution.

Microfluidic Device for Drug Delivery

As an alternative to oral administration, UW-Madison researchers have developed a microfluidic device for delivering a steady infusion of a drug through the skin. The device may take the form of a thin, transcutaneous patch that can be worn for extended periods of time. The device includes a reservoir for storing the drug, and a valve that connects the reservoir to an output needle inserted into the patient’s skin. A pressure source causes the drug to flow from the reservoir to the needle. The key advantage of this design is that the valve can move between the open and closed positions in response to a predetermined condition in the patient’s physiological fluids, providing autonomous control of drug flow.

Method of Concentrating a Sample in a Microfluidic Device

UW-Madison researchers have developed a simple system, based on evaporation, to concentrate a sample in a microfluidic device. The system is composed of a channel within a microfluidic device, which includes a reservoir port and a collection port. The reservoir port can be any type of liquid/gas interface. The channel is filled with the solution that needs to be concentrated. As the solution evaporates from the collection port, the solution in the channel flows from the reservoir port to the collection port. The particles in the fluid concentrate at the collection port and are collected to obtain the concentrated sample.

Method of Forming a Microstructure by Using Maskless Lithography

A UW-Madison researcher has developed a method of using maskless lithography to fabricate microfluidic channels and systems. To create a microfluidic device, a first layer is laid down in relation to a base layer so as to create a construction cavity between them. The construction cavity is filled with a polymerizable material and a desired mask pattern is drawn on a computer. Using the mask as a guide, the computer uses mirrors to direct a polymerizing agent, such as UV light, toward the regions of the device that will be polymerized.

Parts of the device not subjected to the polymerizing agent (including the inside of the channels) are not polymerized. Flushing the non-polymerized material from the construction cavity leaves the desired channel network.

Additional layers may be placed on top of the first layer to create additional construction cavities between them. The additional construction cavities are filled with material, a portion of which is polymerized to define additional channels in the microstructure.

Method of Performing Gradient-Based Assays in a Microfluidic Device

UW-Madison researchers have developed a method for performing gradient-based, high throughput assays in a microfluidic device. The method involves passing two fluids through a channel in a microfluidic system. The first fluid contains a predetermined concentration of particles. Particles from this fluid diffuse into the second fluid, creating a concentration gradient of particles in the second fluid as it flows through the channel. The second fluid intersects a series of targets along the channel wall. Because a gradient in a microchannel is equivalent to a multi-well plate containing thousands of wells, this method is simpler, faster, more efficient and less expensive than traditional high throughput assay systems.

Method and Device for Controlling Temperature inside Microchannels with Chemical Reactions

UW-Madison researchers have developed a method and device for regulating the temperature of a sample fluid inside a microfluidic channel. The microfluidic devices of this invention include a channel for the sample fluid and at least one channel containing a regulating fluid at a predetermined temperature. The regulating fluid undergoes heat exchange with the sample fluid to maintain the sample fluid at a desired temperature.

Endothermic or exothermic reactions chemical reactions, such as those used in commercially available hot and cold packs, are used to manipulate the temperature of the regulating fluid. To change the temperature of the sample fluid, the distance, geometries and properties of materials between the sample fluid channel and the regulating channel(s) can be varied. For example, the sample channel can be designed to run alternately near a first regulating channel and then a second, so that the sample fluid changes rapidly between the temperature of the first regulating fluid and that of the second.

Method of Pumping Fluid through a Microfluidic Device

UW-Madison researchers have developed a novel pumping method in which the surface energy present in a small drop of liquid is used to pump liquid through a microchannel. Like electrokinetic flow, the method of this invention is easy to control and to incorporate into microfluidic designs. But it also provides significant advantages over electrokinetic flow in that it does not denature biological samples or need electricity. In fact, the pumping mechanism is semi-autonomous, requiring only minimal additional hardware that can be incorporated entirely at the microscale. The technique can be used for several applications, including simple pumping, pumping of liquids to higher potential energies, and creating plugs within microchannels.

Method for Creating Constricted Regions inside Microfluidic Channels

UW-Madison researchers have now developed a simple and inexpensive method for fabricating a constricted region inside a channel of a microfluidic device. The method starts by introducing a liquid pre-polymer mixture into the channel. Next, the mixture is exposed to ultraviolet light. This polymerizes and solidifies the mixture at a localized area of the channel to create the constricted region. Features such as porosity or gap size can be altered for different applications.

Microfluidic Devices Fabricated Using Surface Tension and Photopolymerization of Liquid Phase

UW-Madison researchers have developed a liquid phase process to construct smooth, 3-D microstructures.  In this process, a solid is brought into contact with an air-liquid interface to form a shape in the liquid. The liquid, called Norland Optical Adhesive, No. 61, cures upon UV exposure. In this manner, the solid's 3-D shape is made permanent in the liquid.

Method and Structure for Microfluidic Flow Guiding

UW–Madison researchers have developed a structure for guiding microfluidic flow that uses existing channel systems made from glass, silicon or photosensitive polymers to create flow channels. A parallel combination of gas/liquid/gas or liquid/gas/liquid is flowed through the solid channels, creating a virtual wall between the phases due to lack of turbulence.

Method and Apparatus for Measuring the Environment within a Microfluidic Device

UW-Madison researchers have developed a simple and inexpensive apparatus for monitoring the environment within a microfluidic device. The apparatus displays a positive/negative type of readout and is directly fabricated within the microchannel. The readout structure, which consists of dyes imbedded within a hydrogel matrix, functions as both a sensor and a display unit. When specific agents are present, the hydrogel structure swells and releases the dye molecules. Both the size and color of the readout structure change in response to the presence of a predetermined amount of a specific chemical or agent.

Method of Forming a Multi-layer Microfluidic Device

UW-Madison researchers have developed a simple and inexpensive method for fabricating a multi-layer microfluidic device on a base. The method allows stacking of multiple layers and forming of microfluidic channels and components inside the layers during the fabrication process. Each layer can be connected to other layers during polymerization of the top layer. Separate layers that do not connect to any previous layer can also be formed.

Method and Device for Sensing Microfluidic Flow

UW-Madison researchers have developed an improved flow sensor for microfluidic channels. A cantilever beam is placed inside the microchannel at a slight angle to the channel. The flow of fluid around the beam results in different drag forces on the two sides of the beam and causes the beam to bend. From the amount of beam bending, which can be measured optically, a flow rate is calculated.

Autonomous Self-Regulating Microfluidic System

UW-Madison researchers have developed an inexpensive, easy-to-construct and self-regulating system for maintaining the pH and other parameters of a fluid stream in a microfluidic channel. They used stacked micromolding methods and liquid phase polymerization techniques to construct the device, which incorporates a pH-sensitive hydrogel. Expansion and contraction of the hydrogel regulates the flow of a compensating buffer to maintain a chosen pH. The hydrogel composition can be changed so that several fluid parameters can be monitored and regulated.

Microfluidic Actuation Method and Device

UW-Madison researchers have developed a device and method to achieve pumping and mixing of fluid in lithographically manufactured microfluidic channels. The device starts with microstructures within microcavities, which consist of cantilever elements coupled to a substrate that receives vibrations. An ultrasonic vibrator causes the substrate to vibrate. The motion of fluid within the microcavities can be controlled by selecting the shape of the cantilever elements, their position in the microcavity, the spacing of the cantilever elements in relation to the cavity walls, and the frequency of the vibrations. The vibrations can provide acoustic streaming to pump fluid through the cavity. Alternatively, the vibrations can induce small vortices that trap the fluid and mix the particles within it. Vibration may also cause the particles to concentrate in the vortices, thereby creating a local area for photo-detection of antigen presence.