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ALine stays at the forefront of innovation to ensure that we can assist you with cutting-edge microfluidic technology. Take a peek at what we’ve been working on!

Microfluidic Design

How to Design a Microfluidic Device

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Whether the assay protocol is a sandwich immune assays, PCR, and cell-based assays, the same considerations apply in the design development. The objective is tocreate a set of cartridge specifications that will enable design for manufacture while delivering on the required limit of detection, sensitivity within a limit of variability that ensures useful results are consistently provided.

The development process for microfluidics products is especially complex because the biological components have been optimized to perform in standard lab ware, and will need to be re-optimized for a microfluidic device.

Part of the challenge is to organize the development in a logical sequence, focusing on resolving big risk areas first, and part of it is looking at the problem from the desired end result – what do you want this system to do and with what level of accuracy and precision? What’s good enough vs. what exactly mimics what is currently done in the lab with high quality analytical instrumentation?

From Schematic to Functional Microfluidic Device

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Now the development focus is to consider more fully what assay modifications can reduce the number of reagent additions. This has considerable impact on the overall cost of the consumable.

Systems with the need for more than one liquid reagent storage to execute the assay protocol have more than double the complexity in the instrument and cartridge. More moving parts means more opportunities for failure, whether it’s in cartridge manufacture and the need for more QA testing, or in the instrument component complexity and service requirements.

Challenges in Microfluidic Product Development

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Whether the assay protocol is a sandwich immune assays, PCR, and cell-based assays, the same considerations apply in the design development. The objective is to create a set of cartridge specifications that will enable design for manufacture while delivering on the required limit of detection, sensitivity within a limit of variability that ensures useful results are consistently provided.

The development process for microfluidics products is especially complex because the biological components have been optimized to perform in standard lab ware, and will need to be re-optimized for a microfluidic device.

Part of the challenge is to organize the development in a logical sequence, focusing on resolving big risk areas first, and part of it is looking at the problem from the desired end result – what do you want this system to do and with what level of accuracy and precision? What’s good enough vs. what exactly mimics what is currently done in the lab with high quality analytical instrumentation?

Microfluidic Product Design and Manufacturing Challenges

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Much of the development that is done for point of care products involves the application of a ‘fluid circuit’(FC) to move small volumes around that are controlled by considering pressure drops in the system, while life science tools (including the study of cells) often make use of ‘integrated fluid circuit’ (IFC) where geometries and surfaces are critical to function.

As with electronics, the microfluidic ‘integrated fluid circuit’ is managed using a ‘fluid circuit’ to interface liquids and reagents from the bulk (or, to use the electronics analogy, plugging into the wall to get a source of electrons).

ALine's Fluid Circuit Technology

On-Board Valves in Microfluidics

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In this paper we explore the different styles of valves, their control and method of actuation.
The development process for microfluidics products is especially complex because the biological components have been optimized to perform in standard lab ware, and will need to be re-optimized for a microfluidic device.

Valve Performance and Operation

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You must complete a Non-Disclosure Agreement (NDA) to access this document.  Please click on the link above to request the NDA. This paper provides details on the performance of the valve with various materials and cycling conditions and allows us to engineer the valve into a device and readily establish the actuation protocol to acheive optimal performance.

Effect of Channel Width on Air Bubbles and Strategies for Air Bubble Control

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We’ve documented the geometries that tend of exacerbate bubble formation and those that are at low risk for developing bubbles. Managing bubbles is a multi-faceted problem that includes material properties, fluid properties, and actuation protocol.

Modular Designs for Reproducible Performance of On-Board Pumps

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On board pumps have been engineered to deliver fixed volumes as low at 10 uL with less than 5% volumetric variability upon each  cycle. With this level of control, actuation cycles can be created to meter the desired volume of fluid.

Metering and Mixing Evaluated in a Test Chip

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ALine’s Fluid circuit technology has been applied to effect both metering and mixing using simple, scalable approaches that have variations of less than 5%. Complete mixing has been experimentally determined, and reported to support a variety of workflows.

Automated Reagent Dispensing System for Microfluidic Cell biology Assays

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Microscale systems that enable measurements of oncological phenomena at the single-cell level have a great capacity to improve therapeutic strategies and diagnostics. Such measurements can reveal unprecedented insights into cellular heterogeneity and its implications into the progression and treatment of complicated cellular disease processes such
as those found in cancer.

We describe a novel fluid-delivery platform to interface with low-cost microfluidic chips containing arrays of microchambers. Using multiple pairs of needles to aspirate and dispense reagents, the platform enables automated coating of chambers, loading of cells, and treatment with growth media or other agents (e.g., drugs, fixatives, membrane permeabilizers, washes, stains, etc.). The chips can be quantitatively assayed using standard fluorescencebased immunocytochemistry, microscopy, and image analysis tools, to determine, for example, drug response based on differences in protein expression and/or activation of cellular targets on an individual-cell level. In general, automation of fluid and cell handling increases repeatability, eliminates human error, and enables increased throughput, especially for
sophisticated, multistep assays such as multiparameter quantitative immunocytochemistry.

We report the design of the automated platform and compare several aspects of its performance to manually-loaded microfluidic chips.

A Microfluidic Device for Dry Sample Preservation in Remote Settings

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Our well characterized approach can be readily integrated into a product.

Diagnostic Development

Developing Diagnostic Products using Polymer Laminate Technology

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In the development of newer molecular and immunodiagnostic products, panels of tests are launched on a single platform. To accomplish this, complex fluid circuits that perform sample preparation and sample distribution interface with other functional elements. When a device incorporates micro-fabricated components that are injection molded or embossed, changes in the design to optimize performance are carefully considered because of the expense in retooling.

To avoid these costs, modifications are made reluctantly, and other work-arounds may be proposed. While such fixes lower the short-term development costs, the end result may be a merely adequate, not superior, product.

Polymer laminate fabrication offers an alternative that permits iterative and empirical testing without the need for tooling. The result is a superior product that is optimized and well characterized.

The strength of polymer laminate technology is in applications for single-use devices where the fluidic
component needs to perform multiple tasks. The device takes the complexity of the test out of human hands and puts it into a small fluidic card, hence the term Lab-on-a-Chip.

Outsourcing Point of Care Diagnostic Development

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The demand for rapid diagnostic analysis is putting pressure on companies to move testing out
of central laboratories and into the point-of-care (POC) environment. When testing is closer to
the patient, turnaround time, sample touch time and logistics are all reduced. Rapid results
improve patient care and outcomes and reduce required blood and healthcare resources. So, why has it taken so long for POC to be realized?

There a number of reasons. Not every test needs rapid turnaround. Tests at the point of care can be more expensive or less accurate. Some tests are not appropriate for POC because of the need for sample preparation or for trained lab technicians and laboratory controls. But, some of
these hurdles are being overcome by new techniques and technologies.

Sample Prep Series Part 1 – Introduction

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Do you work with any of the following?

• Diagnostics
• Polymerase chain reaction
• Isothermal DNA/RNA amplification
• Microarrays
• Gel electrophoresis
• Molecular cloning

If so, you surely are familiar with the importance of high-quality and high-yield nucleic acid sample preparation. Extracting DNA and/or RNA from sample is the first step for many applications, and any mistakes made here will affect downstream analyses.

Cell Culture

Polymer Laminate Cell Culture Card Supports NASA’s Astrobionics Program

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Laminate construction of microfluidic devices offers a means to incorporate both additive and subtractive manufacturing techniques for the development of multiplexed fluidic devices that have, for example, porous membranes formed-in-place (FIP). Important applications for these hybrid devices includes sample preparation, separations, and containment of samples fed by a single inlet and outlet, such as multiple samples of suspended cells in culture contained in their respective wells.

We describe the development and performance of a fluidic card for the NASA Ames GeneSat-1 program for autonomous cell culture experiments in space. The fluidic card was constructed as a multi-layer laminate of acrylic and biocompatible bonding adhesive, using laser ablation to form the channels with porous membranes placed at the inlet and outlet of each sample well to contain individual samples of E. coli and prevent cross contamination.

Microfluidic Device for Mechanical Dissociation of Cancer Cell Aggregates into Single Cells

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Tumors tissues house a diverse array of cell types, requiring powerful cell-based analysis methods
to characterize different cell subtypes. Tumor tissue is dissociated into single cells by treatment with proteolytic enzymes, followed by mechanical disruption using vortexing or pipetting. These procedures can be incomplete and require significant time, and the latter mechanical treatments are poorly defined and controlled. Here, we present a novel microfluidic device to improve mechanical dissociation of digested tissue and cell aggregates into single cells. The device design includes a network of branching channels that range in size from millimeters down to hundreds of microns.

Live Mammalian Cell Arrays

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High-content assays have the potential to drastically increase throughput in cell biology and drug discovery, but handling and culturing large libraries of cells such as primary tumor or cancer cell lines requires expensive, dedicated robotic equipment.

We developed a simple yet powerful method that uses contact spotting to generate high-density nanowell arrays of live mammalian cells for the culture and interrogation of cell libraries.

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