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Jan 15, 2012 (Vol. 32, No. 2)

Lab Automation Solutions

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    CellSpot technology isolates cells magnetically on a small disk that forms the roof of Fluxion Biosciences’ IsoFlux microfluidic flow channel. Once a run is complete, the disk is removed from the flow channel, and the intact target cells are transferred into a microcentrifuge tube in less than 20 µL, ready for downstream assays such as PCR, FISH, immunoassays, and sequencing.

    Academic and industrial laboratories are under pressure to be more productive with limited resources. Laboratory automation is a critical and effective solution to the needs of modern science.

    It is difficult to imagine a modern laboratory without at least one piece of automated equipment. Increased throughput and decreased volume dictate the need for efficient robotics and precise connectivity between analysis steps. The former “Lab Automation” conference, now known as SLAS, takes place in San Diego next month and will spotlight the breakthroughs that push the boundaries of laboratory development processes.

    Last year, the Association for Laboratory Automation merged with the Society for Biomolecular Screening (SBS), launching the Society for Laboratory Automation and Screening (SLAS). SLAS is dedicated to advancing scientific research and discovery through laboratory automation and screening technology. Technologies profiled in this article represent just a few highlights from this exciting field.

    “Most early microfluidic applications focused on separation and analysis of biochemical molecules,” comments Cristian Ionescu-Zanetti, chief technology officer at Fluxion Biosciences. “However, many cell-based assays also benefit from the advantages of the microfluidic approach, for example applying the shear flow to maintain physiologically relevant conditions or addressing single cells.

    “Our development focused on cell-based assays to achieve the throughput and cost of biochemical assays with optimal biological relevance.” Fluxion Biosciences designed several proprietary microplates to enable cell-based assays in the microfluidic format.

    “Biomolecular microfluidics trends toward lab-on-the-chip format, where all the valves and processors are integrated on the disposable chip. While this approach provides maximum automation, it also leads to high costs of disposables,” continues Dr. Ionescu-Zanetti.

    “We pursued a radically different philosophy of product development: lab-off-the-chip.” Fluxion plates contain a network of passive microfluidic channels, while the controls reside within the external hardware station.

    The movement of fluids is driven by air pressure applied to the sample loading chambers. The pressure pushes the sample out of the chamber and through the microchannel. If the cells are bound to the magnetic beads, magnetic capture occurs within the microchannel. The same microchannel may be connected to various other chambers, pneumatically actuated as needed for a particular application.

    In addition to cell separation, Fluxion’s applications include cell imaging, automated patch clamping, cell migration assays, drug activity studies, and others.

    “Isolation and concentration of circulating tumor cells (CTCs) hold tremendous potential in cancer companion diagnostics,” says Dr. Ionescu-Zanetti. “It is also technologically challenging. Microfluidics enables passing a few cells at a time through the separating region while maintaining the individual cell microenvironment.”

    The company’s IsoFlux™ Rare Cell Access System captures the labeled cells on a small polymeric disc that forms the roof of the microfluidic separation channel. When the disc is decoupled from the channel, the cells remain in a small droplet ready for downstream assays.

    This combination of microfluidic enrichment and delivery in a small volume opens the doors for continuous cancer monitoring via “liquid biopsy”. While frequent tissue biopsies to monitor cancer recurrence are often not practical, identification of tumor cells via simple blood draw may become routine in clinical patient management.

  • Point-of-Care Diagnostics

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    A programmable bio-nano-chip system customized for measurement of cardiac biomarkers using oral fluid samples by researchers at Rice University.

    “I tend to agree with Dr. Ionescu-Zanetti about the importance of the cost of disposables, but also want to emphasize that there is a series of additional key requirements for point-of-care diagnostics,” says John McDevitt, Ph.D., Brown-Wiess professor of bioengineering and chemistry, Rice University, and scientific founder of Force Diagnostics.

    “We are now targeting the development of transformative medical microdevice technologies capable of producing lab quality results anywhere. We estimate that the cost of point-of-care applications, especially for resource-poor areas, should be just a few cents. Ability to mass produce the reagents, simplify chip design, and use plastics instead of silicone is how we can bring the cost down to this target range.”

    Dr. McDevitt’s lab develops programmable bio-nanochips that combine novel microsensors with artificial intelligence. These sensors, which have a capacity to learn, allow for rapid analysis of just about any soluble chemistry, including biological molecules and chemical compounds, and can cover major cell-based assays.

    For soluble chemistries, in the product’s reaction core are porous agarose beads woven from nanometer-size fibers. For cells, supported membranes are employed. The capture of analytes and cells is optimized by manipulating the pore and bead sizes. Every 30 nanometers of each fiber is coded with a capture reagent, such as an antibody.

    “The bead is essentially a microsponge with a nanonet, with binding points distributed throughout. This structure enables 10,000-fold signal amplification in comparison with a standard ELISA plate,” says Dr. McDevitt. A single bead is loaded in each well of a plastic chip; each bead may have different derivatization, so that multiple analytes may be analyzed simultaneously.

    “Our plug-and-play design can be utilized in place of almost any analytical instrument used for discovery, validation, or clinical applications. If the same tool is used throughout the development pipeline, the cost and interfacing complexities are eliminated, and the process can be significantly accelerated,” says Dr. McDevitt.

    “The simplicity of this platform—which is now in six major clinical trials—will enable many more biomarkers to be developed for clinical applications.”

    Simple sampling interface is another characteristic feature of Dr. McDevitt’s bio-nanochip, he asserts. To run the HIV diagnostic chip, a drop of blood is obtained by a needle stick and transferred into the key-hole port by a simple capillary tube. Analysis is performed by a portable “biotometer” with minimal user involvement.

    With the aid of Force Diagnostics, the HIV diagnostic system is now in a clinical trial in Africa. Another advanced bio-nanochip application is POC diagnosis of heart attack based on gum swab. Multiple other salivary diagnostic products are in development.


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