ALine, Inc. – Accelerated Microfluidic Development

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A Systems Approach to Microfluidics Products

The complexity in Microfluidics Product Development originates in the requirement to integrate and optimize the functional performance of a variety of dissimilar components that are coupled together in close proximity.  It involves a combination of biological and materials science and engineering to create a robust product solution. Any product that performs tests and measurements is fundamentally an information producing system. The quality of the information depends critically on how well each of it’s disparate components are harmonized to become ‘more than the sum of the parts’.

 

This is where an understanding of the science is critical to success. In microfluidic systems, the high surface area to volume, shorter diffusion paths, and smaller thermal masses can reduce the time to reach the measurement end point. This is one advantage of microfluidic systems. However, if in performing a multi-step assay, inadequate washes, or an incorrect washing approach is implemented, the opposite will occur. Instead, the system will exhibit degraded sensitivity or dynamic range, or have greatly increased testing times and produce poor quality information. Some poorly designed systems require very high volumes of wash fluid which creates a large mismatch in the fluid components.

 

rapid-prototypingAnother feature of some more complex tests is to try to translate the exact protocol done in bench top instrumentation or on robotic systems, into a device. This can lead to half a dozen reagent storage packs or more followed by cumbersome mechanical interfaces. Just remember, each component of the system that requires some sort of separate performance validation is adding complexity, and a risk for failure. A better product strategy is to optimize the assay to require no more than three separate reagents.

 

From an engineering and design for manufacturing perspective, the fewer mechanical parts there are, and the lower the tolerances for the interconnections of these components, the better. Some simple things to remember include taking advantage of the force of gravity…it’s free and it’s dependable!  Another simple pointer regarding cartridge alignment is to never design the alignment of the cartridge into the instrument along an edge. This creates constraints on the precision of the disposable component, the very thing you are trying make as inexpensively as possible.

 

Some of the tougher engineering issues to solve involve the ability to do thermocycling. Here the science, engineering, and system design all need to happen together to ensure that a design feature in one component doesn’t add complexity or risk to another component.  Even the nature of the nucleic acid detection test itself can affect the system design and choice of materials, so it’s prudent to map out reasonable specifications on performance of the assay at the outset and chose the disposable design, and interface to the detection and other electro-mechanical components early.

 

ADEPT+ cartridge

Our approach to supporting systems engineering is to design and develop sub components instruments, such as the ADEPT and ADEPT+, that can be customized and modified to test the integration of each component. Our instruments include cartridge clamping, modules for pneumatic, pumping, and thermal control to provide a means for semi-automated control of the assay being performed. By doing this early in the development program, the overall development risk is lowered and the quality of the final product enhanced.

Learn more about our systems approach by viewing our new Systems Engineering Brochure

Experts In the Science and Engineering of Microfluidics

ALine’s expertise in microfluidics design and production, integrates custom fluid handling in a single-use device with semi-automated instrument control.

Our toolbox of well characterized on-board valves, pumps, metering, mixing, and de-bubbling strategies perform robustly with manufacture scale up.

Starting with an assay that is performed in a microtiter plate, ALine translates the manual workflow into a semi-automated process in a microfluidic device.

In as little as 60 days, you can be running your target assay in a customized microfluidic device with automated control in an instrument, and begin optimizing the device design and reagents to achieve proof of principle..Lab on Chip integration with mcirofluidics

 

Lab-on-a-Chip Automation SLAS2016 – Booth 1100

SLAS2016 January 25 – 27th, San Diego Convention Center
Learn about our unique solutions to Lab-on-a-Chip products with Instrumentation to support Plug and Play Automation.
SEE the ADEPT Controller with Pressure Sensors, Regulators, and Integrated Thermal control, Vacuum and Pressure Sources

top view breadboard instrument

 

 

 

 

 

 

Flexible and Easy to Customize Instrumentation that enables:
  • Fluid Handling
  • Thermocycling
  • Flow/Pressure Control
  • Electroactive Detection
ALine is proud to partner with Elveflow to develop custom microfluidic solutions 
An ElveFlow pump will be available at the booth. Check it out.
OB1 Microfluidic Pressure Controller MK3

OB1 Microfluidic Pressure Controller MK3

  • Droplet Generation
  • Cell culture
  • Droplet PCR

3D Printed Microfluidic Connectors Solve the Chip-to-World Interface Problem

3D printing lends itself to the manufacture of components which are tailored to specific needs of the end user. For example, an early application of 3D printers was in the manufacture of custom hearing aid shells, designed to fit comfortably into the ear of the individual patient. In dentistry, it has been used to create crowns, mouth guards and braces. Applications in the Life Sciences and Medical Device industry continue to grow as the print resolution, and available materials expand. Exotic applications in tissue engineering, with the goal of producing organs and tissues with defined composition, are being explored.

For applications in microfluidics, ALine has developed a series of 3D printed fluidic connectors that integrate with custom microfluidic devices produced with rapid prototyping techniques such as lamination, or micro-machining. By comparison, commercial connectors, such as luer-locks and hose barbs, have only a limited choice in terms of geometry, require a large footprint for multiple inputs, and introduce dead volume into the fluidic network. Some tubing connectors with compression fittings are available with low dead volume, but are priced so high they often cost more than the device itself.

3D printed fluidic connectors greatly expand the options available to bridge the “chip-to-world” interface. The micro-to-macro interface between the microfluidic chip and the supporting instrumentation has always been a difficult engineering problem. This interconnection issue sometimes leads to the assertion that microfluidics really represents a “Chip in a Lab” rather than a “Lab on a Chip”.

With the development of low cost, high resolution 3D printers, the interface problem can be overcome with simple, easily customized connections. 3D printed connectors with multiple inputs occupy a much smaller footprint and minimize the dead volume. Connectors are customized for the specific device configuration to allow 90 degree of co-planar connections. Hose barbs for flexible tubing connections, as shown in Figure 1) and 2), are a typical application and are readily assembled to the microfluidic using biocompatible pressure sensitive adhesives.

3D printed connector integrated into device

Figure 2) Low Dead Volume Connection Co-planar with the Microfluidic Device

The process to produce these connectors is suitable for rapid prototyping and low to mid-volume manufacturing. The turn-around time is typically a few hours because the process does not involve any machining or production of molds. 3D designs are created using computer automated design (CAD)

3D connector

Figure 1) 3D Printed Multiplexed Tube Connection

software. The printer selectively cures 2D layers of a UV resins, building successive layers which produce 3D objects. Multiple resins are available allowing for choice of color, mechanical properties and biocompatibility. Typical batches include 10-20 connectors per 3D print run with scale-up to 100s and even 1000s easily achieved with no change in equipment.

ALine’s approach of combining 3D printed connectors with our proprietary laminate fabrication technology provides design flexibility in the development of custom microfluidic devices. With the advanced 3D printing tools now available, we solve the problem of the “Chip-to-World” interface with customized connectors, tailored to meet the unique design and functional requirements of each microfluidic application.

For more information contact:  Stefano Begolo, Ph.D.;  sbegolo(at)alineinc.com

ALine Is Growing!

We are pleased to announce that Dr. Stefano Begolo, a recent post doctoral fellow in Rustem Ismagilov’s lab, is joining ALine, in early August 2015.

Stefano was a customer while he was working on the Slip Chip technology at CalTech and he enjoyed interacting with us enough to be interested in being part of the team!

Stefano’s expertise in microfluidics, his familiarity with assay development and PCR, and his interest in working on a variety of client programs will add tremendous depth to our offering.

With his expertise in 3D printing, we plan to offer this capability along with our popular laminate technology.

Click here to learn more about Stefano.

Integrated & Automated Fluid Actuation

The ADEPT Automates Potentiometric Measurements Using a Microfluidic card connected to an Ion Selective Electrode (ISE) Sensor Array

We combined a low noise multichannel electrometer with the ADEPT pneumatic control instrument for sequential testing of an ISE sensor array to measure Na+, K+, and pH using an external reference. The test system includes an 8-channel ADEPT instrument with the electrometer housed in a shielded box. A slide in port for the microfluidic test card reduce ambient noise and the automated routine for delivering three different analyte solutions of Na+, K+, and pH, provided a controlled environment for the ISE measurements.June Newsletter Figure 1

Read our latest Newsletter to learn more.

George Lauro, Distinguished Tech Entrepreneur, Joins ALine’s Board

6 x 96 valve manifold

ALine’s Advanced 6 x 96 Valve Manifold

ALine, a leading developer of advanced Fluid Circuit products and solutions is pleased to announce that George Lauro has joined its board. George has 25 years of experience as a technology entrepreneur, operating executive, and venture capitalist. He has built several tech companies from early stage to high value exit (M&A or IPO). George is Founding Partner of Alteon Capital, a Technology Venture Development firm based in Cambridge, MA. He was Managing Director at Wasserstein Perella and head of West Coast technology investing, and was a Partner at Techfarm Venture Capital in Silicon Valley. He led and syndicated 18 private equity financing rounds and control deals, raised over $100M equity financing for portfolio companies and completed over $1 billion in M&A transactions. George will work with ALine’s management team to develop and execute its accelerated growth strategy.

George Lauro added, “I am delighted to be joining ALine’s Board. I believe that the Company’s proprietary functional and material set and strong design and process team positions it for significant growth in the microfluidics and Lab-on-Chip sector. I look forward to helping the Company and team achieve this potential.”

Dr. Leanna Levine, President and CEO commented, “We are very happy that George recognizes the growth potential for our business. His distinguished career and experience in venture capital, operations and entrepreneurship are a tremendous asset to ALine. We are pleased he recognizes ALine’s unique and valuable position in the microfluidics market space.”

About ALine
ALine is a leading microfluidic and Lab-on a Chip engineering and manufacturing company serving the Life Science, Medical Diagnostics, and Analytical test markets. Over the past 7 years, we’ve designed and brought to volume production several advanced microfluidic solutions for major customers in several industry sectors, including NASA, JPL, Abbott, GenMark, and Iris Diagnostics (Beckman Coulter).

ALine’s array of materials and fabrication processes give us the broadest design space of any Microfluidics company in the world. We provide prototype-to-production solutions and execute all steps of microfluidic solution development from initial design through prototyping up to high volume manufacturing. Our unique processes enable one week turnaround on prototypes of sophisticated microfluidic and Lab-on-Chip devices that are scalable for volume production.

ALine was founded in 2003, and is ISO9001:2008 certified.

Breadboard Instrumentation

Visit us at booth #4 at LOAC WC in San Diego, Sept. 18th & 19th.

One of the more complex challenges in developing a Lab on a Chip product is integrating the instrument with the microfluidic chip.

Along with our ability to rapidly prototype microfluidic devices, moving quickly through the design-build-test cycle, we offer mechanical, electrical, and software engineering to integrate the microfluidic into a small stand alone system as described in our instrumentation capabilities brochure.

For a preview of our capabilities, see our September Newsletter

Newsletter August 2014

View our August Newsletter

– Learning Lab at Micro-TAS October 29th, 2014

– ALine’s sealing and lidding capabilities

– ALine’s partners for on-Chip reagent storage

ChroMedX Engages ALine to Develop the HemoPalm

July 29, 2014 – Toronto, Ontario – Monarch Energy Limited (CSE: CHX) (OTC: MNLIF)(“Monarch” or the “Company“) is pleased to announce that its wholly-owned subsidiary ChroMedX Ltd. has engaged ALine Inc. of Rancho Dominguez, CA as its primary contractor for the development of the Company’s HemoPalm cartridge and analyzer technology. The goal is to complete construction of the prototype cartridge and analyzer to demonstrate functionality of the system by the first quarter of 2015. ALine has expertise in the engineering, prototyping and manufacturing of microfluidic cartridges used in the life sciences and in vitro diagnostic fields. ALine Inc. was founded by current President and CEO, Leanna Levine, Ph.D.

 

Wayne Maddever, Ph.D. P.Eng, President and CEO of ChroMedX Ltd. said, “The experience and expertise of Leanna and her ALine team make them the perfect partner for the development of the HemoPalm system.”

 

Leanna Levine, Ph.D., President and CEO of ALine said, “We are excited about the potential for ChroMedX’s technologies and are pleased to be a part of this development.”

 

HemoPalm Technology

The HemoPalm system is comprised of a disposable cartridge and a handheld analyzer. The system measures co-oximetry, blood gases and electrolytes, in a patient’s blood, and the resulting analysis can provide a complete assessment of a patient’s acid-base and oxygenation status at the point of care (POC). The leading competitors in POC testing require a second analyzer to provide CO-oximetry, which is the gold standard for measuring hemoglobin oxygen saturation and total hemoglobin. The ability to provide all the measurements described above in a single central laboratory analyzer has been available since the 1990s. ChroMedX intends to be the first company to provide these measurements in a single handheld analyzer.

In addition to ALine Inc., ChroMedX has engaged additional consultants with expertise in microspectrometry and biosensors to compliment the development team led by James Samsoondar, Ph.D., ChroMedX Chief Scientific Officer.