By Robert M. Frederickson
Dec 2005 / Jan 2006 | As mundane as the topic of fluid management may seem, it is big business. Labcyte, a developer of microfluidic systems, has estimated a market size of $1 billion annually. Pharmaceutical developers and academic researchers worldwide spend very large sums of money on plastic consumables and the automated robotic systems that move and dispense liquids in a high-throughput format.
Microfluidic systems tend to rely on small channels to move fluids through a plastic or glass matrix, either in a chip or capillary format. Most devices rely on pressure, charge, or capillary action to move liquids in these tiny channels, such as is found in products offered by Caliper Life Sciences or Agilent’s Bioanalyzer systems, for example.
Labcyte’s approach, however, does away with both channels and capillaries, replacing them with, well, nothing. The company has created a device called the Echo 550 Liquid Handler that can make direct microplate-to-microplate transfers of droplets of liquid as small as 5 nanoliters using a new “touchless” transfer technology. Based on focused acoustic energy, the process avoids contact between the transducer (which converts energy to sound) and the fluids being moved. Essentially, a fluid droplet is “vibrated” onto a new surface with great accuracy and precision — with coefficient of variation values of less than 5 percent. Droplets emerge from wells of microplates through a simple upwelling of fluid in response to the pressure of focused acoustic waves below the fluid surface. Users can control the volume of the drops by changing the frequency of the sound waves.
THEORY AND COMPOSITE: Snapshot of focused acoustic theory
(L) and stroboscopic image composite (R) of 150 ejection events,
showing the high reproducibility of the ejections.
The technology is well suited to high-throughput biological applications where large numbers of different fluids must be transferred rapidly and sequentially. Elimination of time-consuming wash steps both reduces the use of solvents and saves time. The system is designed for the replication and reformatting of compound libraries, as well as plate compression or expansion from 96-, 384-, and 1,536-well microplates, making it ideal for processing expensive and limited compound libraries. Since the ejected droplet touches nothing on its trip up to the microplate, the possibility of cross-contamination is eliminated.
Drops as large as 10 microliters have been transferred with this technology, and larger volumes can be moved as multiple drops. The process is a gentle one, and Labcyte has shown that it can transfer proteins, high-molecular-weight DNA, and even live cells without damage or loss of viability. This feature makes the technology well suited to applications in proteomics and cell-based assays.
Labcyte is also developing applications for the preparation of samples for MALDI mass spectrometry. Using the same technology as the Echo 550, the Portrait 630 system deposits small amounts of matrix directly on very thin (10-20 microns) slices of tissue that are then analyzed for the presence of a particular protein or drug metabolite. The process essentially marries tissue array technology with high-throughput chemical analysis, retaining information on position of a particular analyte within the tissue. Labcyte is currently taking orders for beta testing of the Portrait 630, which they hope to ship in May 2006.
Seven top pharmaceutical companies have already purchased at least one Echo system. Bristol-Myers Squibb purchased two additional Echo 550 liquid handlers in 2005, following the completion of a successful beta test program on its first instrument. Novartis, AstraZeneca, GlaxoSmithKline, and Amgen have also purchased systems.
Integratability is always a concern with fluidic systems. A particular challenge for integration of the Echo 550 has been the need for a receiving plate that is essentially upside-down, since fluids are transferred upwards. Anticipating this issue, Labcyte created a special “wrist” on the device that allows plates to be rotated into the correct orientation for compatibility with existing automated systems.
The Echo system has been integrated with Velocity 11’s Biocel, and this integrated system is in use at Novartis. Thermo Electron’s CRS division systems, such as the Catalyst Express, the CRS F3 or CataLyst5 robot, and the CRS Dimension4 automation platform, as well as workstations offered by Process Analysis and Automation, a U.K.-based provider of automation and measurement technology, have also both been integrated with the Echo 550.
Robert M. Frederickson is a biotech writer based in Seattle. E-mail: email@example.com.