By Robert M. Frederickson
December 15, 2003 | MP3 downloads off the Internet may be wreaking havoc with the sales of CDs at your local music shop, but if the plans of Sweden's Gyros AB are successful, you could be seeing a lot more of this compact technology platform in a research lab near you.
Gyros has released the Gyrolab Bioaffy, its most recent CD-based proteomics microlaboratory. Researchers can use the product on the updated Gyrolab Workstation, which now incorporates laser-induced fluorescence detection that allows them to run established sandwich-based immunoassays for protein quantification at the nanoliter scale. Gyros hopes to exploit the extensive libraries of target-capturing proteins that are being offered by collaborator Affibody to further the diversity of this new microlab format.
Gyros, founded in 2000, takes advantage of a decade of research in miniaturization and microfluidics. The company's modus operandi combines centrifugal and capillary forces with precise CD microfabrication to integrate genomic and proteomic assays into application-specific Gyrolab microlaboratories. The advantages of miniaturization of biological separation and assay techniques have long been appreciated. This approach allows researchers to conserve biological samples, take advantage of the often superior reaction and diffusion kinetics at the micro scale, and automate and integrate the analysis of multiple samples in a controlled and parallel manner.
| Revolutionary forces: Gyrolab Bioaffy uses as little as 500 nanoliters of sample to generate each data point.
Gyros' unique "spin" on the microlab is quite literally just that — to move fluids through complicated reaction chambers by making use of the centrifugal forces generated by the spinning of a CD. This contrasts with the forces used by competitors — such as Fluidigm, Surface Logix, Eksigent, Nanostream, and BioMicro Systems — to drive movement of soluble biological reagents through predominantly chip-based platforms, which include capillary action, pressure, and electrophoresis.
Precise microfabrication exploits the interplay between capillary and centrifugal forces with specific surface chemistry to affect and control the movement of samples and reagents through the device. For example, a hydrophobic surface within a fluid bottleneck is designed to prevent liquid from moving beyond a specific point within the microstructure. However, a second spin, at higher speed, creates a G-force sufficient to drive the liquid over the hydrophobic break. The microfabricated units comprise various microstructures that perform specific tasks in the application. Examples include chromatography columns and chambers for enzyme reactions or cell growth.
The first commercial products from Gyros are focused on proteomic applications within drug discovery, a market that continues to demand high-throughput and high-information-content technologies so as to speed and reduce costs within the discovery pipeline. At various stages during the drug development process, proteins need to be quantified accurately, for example, when monitoring proteins during target and lead validation. Another example occurs further downstream, during comparison of the profiles of putative biomarkers in small animal models. These time-consuming and costly investigations can be reduced to days rather than the weeks it can take when using more protein in a single sample.
A microlaboratory can process hundreds of samples in parallel, under the control of the Gyrolab Workstation. The workstation controls the entire process, transferring samples and reagents into the microlaboratory and driving samples through every step of the application by spinning the CD. Working at nanoliter scale, Gyrolab Bioaffy enables protein quantification in a format optimized for working with small volumes and many samples. The most commonly used techniques for protein quantification are immunoassays. In the first Gyrolab Bioaffy CD, users are able to miniaturize and integrate existing sandwich immunoassays, designing single or multiplex assays.
The launch of Gyrolab Bioaffy takes the company a step toward fulfilling its early claim that its unique technology platform would allow the development of multi-application instruments. Both Gyrolab Bioaffy and Gyrolab MALDI CD microlaboratories can be run on the same workstation.
Gyrolab MALDI comprises an integrated process for sample preparation for MALDI mass spectrometry, a technique in wide use for protein and peptide identification. Gyrolab MALDI SP1 concentrates and purifies protein digests used for identification and crystallizes them directly onto MALDI target areas on the CD. The CD is then placed directly into the mass spectrometer for sample analysis. In some respects, the product provides loosely the same functionality as Fluidigm's Topaz Crystallizer, which automates the metering, mixing, and isolation of protein crystallization experiments (see "Bringing Integrated Circuits to Life," Feb. 2003 Bio·IT World, page 70).
Each Gyrolab MALDI processes 96 samples simultaneously. Earlier this year, the company introduced a modified version of the MALDI CD, the Gyrolab MALDI IMAC, which offers users a solution for detection of phosphorylated peptides. Duplicate samples are subjected to the same process, but with the addition of an enzymatic step that removes phosphate groups from one sample before crystallization. Phosphorylated peptides are detected by comparing mass spectra from phosphorylated and dephosphorylated samples.
While kits compatible with MALDI-TOF instruments from Bruker Daltonics and Kratos Analytical are currently available from Gyros, kits for interfacing with instruments from other manufacturers are under development.
Robert M. Frederickson is a biotech writer based in Seattle. He can be reached at email@example.com.