ALine has developed an engineering tool box of microfluidic functions and supporting instrumentation to quickly address a range of performance needs for microfluidics-based products.
On-Board Valves and Pumps
More than 15 years ago, ALine pioneered the invention and reduction to practice of practical, reliable, and easy to manufacture pneumatically controlled on-board diaphragm valves and pumps in a low cost, scalable laminate manufacturing process.
We led the industry in creating and implementing these well-characterized and robust on-board valves and pumps, demonstrating a range of performance well within the requirements for diagnostic and life science tools applications. These engineered components act as the core of commercialized products for current and former ALine customers.
They are so reliable and effective that competitors have tried to imitate them, but still have to rely on ALine’s designs which show up in their trade show displays.
Applications Include:
Chemical Processor
A chemical processor for addressing any combination of inputs, combining them and delivering them to any output. This design recapitulates the function of Mathies-style valves made in glass with PDMS, in low cost, easy to manufacture plastic laminate components. This work was done with Peter Willis at the Jet Propulsion Lab in Pasadena.
Meter and Distribution Method
A method to meter and distribute a single sample into a multiplexed testing platform.
Multiplexed Reagent Distribution Manifold
A multiplexed reagent distribution manifold, described in our case studies. This array of 144 valves in a semi-consumable product made using laminates and injection molded components, eliminates the need for a large, high dead volume, expensive and complex fluid distribution manifold using traditional solenoid valves and thermally bonded acrylic manifolds. This manifold is currently a manufactured component for BioRep’s Perifusion System.
Serial Dilution Manifold
A serial dilution manifold to create a dose response curve or understanding the sensitivity of an assay over a range of concentrations.
We have successfully extended the application of our valve technology for a variety of valve geometries and functions that are currently part of patent applications. We continue to extend the application and further characterize the performance of these valves over a range of materials and applications that show their enduring value in microfluidic applications.
Metering, Mixing, De-bubbling and Detection (M2D2)
The four key functional requirements for a range of microfluidic applications can be summed up by M2D2. ALine has perfected these functional requirements using customized off-the-shelf fluidic components from our engineered toolbox of fluid circuit components.
What we've shown in repeated applications is that we can:
Meter
Meter to volumes of 5 ul with less than 2% variability.
Mix
Mix using simple fluid circuit elements that can be active or passive mixers.
Debubble
Mitigate air bubbles, the bane of every microfluidic device design and application.
Detect
Design detection geometries for optical or electrochemical detection that optimize the sensitivity and limit of detection.
Flow Cells and Imaging Chambers
A frequent request we have had over the years is for some sort of a flow cell that covers a microscope slide, silicon wafer, or printed circuit board for varied functions.
What makes this range of applications possible? ALine’s ability to create controlled height flowcells that readily attach to standard glass slides, silicon or PDB sensors using low-cost off the shelf material sets that have been vetted for biological applications.
Some of the potential applications:
VIscosity and Controlled Shear
Measure viscosity.Induce controlled shear to observe cell stress.
40x to 60x imaging through a plastic consumable
Image viral particles from heterogeneous samples.
Real-time measurement of oxygen exchange in hemoglobin
Spectrometrically measure real-time exchange of oxygen with whole blood in a microtiter plate reader outfitted with precision oxygen control, a microfluidic alternative to a tonometer.
Flow Cells
Flow cells for NextGen sequencing applications.
Convert static well-based assays to flow-based assays
Convert a range of assays from static, microwell-based measurements to flow-based measurements in a controlled fluid flow regime.
Cell Culture Devices
Cell culture devices for applications ranging from cell culture in space, to organ on chip applications with specialized membranes and geometries suited to the cell type.
Sample Prep and Filtration
In point of care diagnostics, focus on downstream detection can sometimes overshadow the critical upstream sample prep requirements for processing complex and precious samples. Quantitative detection requires sample metering to allow calibration to a standard. Whether the sample is blood, urine, or other biological source, having engineered solutions for the critical metering step is key to the overall success of the product.
Our passion to stay at the cutting edge of the science and engineering of materials and sample processing technologies. When coupled with our experience sourcing the best materials and our design acumen, we ensure that the diagnostic measurement is poised to achieve the downstream detection sensitivity and limit of detection.
In many sample prep applications, separation of plasma from whole blood, or pre-filtering to remove interferants is key to a successful analysis. We have years of experience understanding the right geometry and surface area of membrane needed for the application.
Membranes in Microfluidics
Membranes, porous membranes and filtration media are common components in microfluidic products. They provide functions ranging from gas exchange to reagent storage, separation of blood components to barriers for diffusive exchange of nutrients in cell culture.
Membranes are available in a wide range of polymeric and non-polymeric materials. Access to information on picking the right membrane for an application comes from the scientific literature or from suppliers such as Sterlitech, who provide references for the application of different types of membranes on their website.
For applications specific to microfluidics, ALine has more than 35 years of experience in the implementation of membranes for bioanalytical applications, including the sourcing, integration and evaluation of performance. The range of applications ALine has supported are outlined below.
Once a choice of membrane is determined, the method of integrating the membrane can impact its functional performance and the scale-up cost of manufacture. In general, there are two approaches to integrating membranes into microfluidic devices:
- heat staking or adhesive bonding of a die cut membrane disk
- lamination of the membrane sheet into the microfluidic device with thermal or pressure sensitive adhesives as part of a batch or roll-to-roll manufacturing process
The choice depends on the type of membrane, its function in the product and sensitivity to the cost of goods for manufacture.
Membrane Type and Applications:
Flexible Non-Porous Membranes
- pneumatically controlled diaphragm valves and pumps
- gas exchange components for real-time measurement of oxygen exchange
Macro-Porous Membranes
- containment of non-adherent cells in a multiplexed cell culture device
- precision fluidic resistors in a fluid circuit to create simultaneous filling of a series of chambers
- barrier to bacteria in microfluidic flow systems
- separation of plasma from whole blood for sample prep
- air venting in fill metering of fluids in microfluidic circuits
- active de-bubbling of fluids
- support for electrodes in gas detection
Track Etch Membranes
- passive cell separation – sperm cell sorting
- organ on chip, stacked multichambered devices for tissue culture with continuous flow
Porous Media
(Sintered, Fibers, Foams)
- Liquid reagent storage
- Controlled delivery
- Vacuum drive for fluid circuit filling
- Venting
Depth Filters
(Pads, Cellulosics)
- Glass fiber capture of nucleic acids
- Glass fiber whole blood filtration
- Dry reagent storage
- Waste fluid containment
Rigid, Ultrathin Nano-Porous Membranes
(Silicon)
- Cell culture, organ on chip
- Study of cell migration through controlled nanopores
Sensors And Optical Interfaces
Our Technical Articles
We’ve described the development process in our technical articles, and we emphasize again here that success in developing a bioanalytical tool requires thinking about the detection scheme and geometries required early in the roadmap to product development. Or as we have framed it, start from the end. What this means in the practical execution of the development program is that we develop the detection volumes and instrument interface and test with a range of concentrations of spiked analyte using analytical detection instruments such as plate readers.
Working with detection geometries for optical detection on the 96 well footprint makes it easy to fabricate and optimize the detection chamber, as well as benchmark its performance against a known standard in analytical instrumentation. When the detection optics are integrated, it’s optimization can be readily benchmarked.
Wearables and Flexible Electronics
Our Wearables Case Study
ALine provides key support for Epicore Biosystems in the DFM, and pilot production of their family of sweat-patch products.
Epicore has developed ‘skin-like’ wearable microfluidic solutions that are capable of non-invasively measuring sweat biomarkers, skin health, and physiology, in-real time.
Founded in 2017 as a spinout company from Northwestern University’s Querrey Simpson Institute for Bioelectronics and John Rogers Laboratory, Epicore has partnered with multiple Fortune 500 companies, the Department of Defense, and leading research hospitals to drive personalized hydration and skin care management with wearable microfluidic products.
