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August/September 2011
Microfluidics-Based Separations Technology for the Analytical Laboratory
Geoff Gerhardt, Ph.D. Sr. Director, Instrument Research, Waters Corporation
• PhD in Analytical Chemistry, University of Saskatchewan • 25 yrs in analytical chemistry, the last 15 yrs in technology development. • Currently manages the Instrument Research Group at Waters, a team of innovative scientists and engineers responsible for developing Waters’ next-generation separations technologies.
A seminal paper was written by Manz et al. (1) identifying the use of possibilities of using ‘chip based technology’ within an analytical instrument. When did you as a scientist first think that ‘chip technology’ could be a useful addition to analytical instrument design and separation science in particular?
In the early 1990’s we saw a lot of enthusiasm for the “Lab-on-a-Chip” concept. And at the time, the concept of integrating multiple laboratory processes like sample prep, cell lysing, digestion, separation and detection onto a single microfluidic device looked technically possible.
However, as researchers began to develop these microfluidic systems, integrating these various functions onto a single device proved difficult. Each lab process used different technologies, such as sample prep or digestion, compared to technology used for separation and detection. What started out as a single device became a hybridisation of a variety of technologies with a host of complex interfaces.
Early microfluidic devices showed promise until they were applied to real world applications. The small volumes, picolitres rather than microlitres, made maintaining chromatographic resolution and transporting the analytes to an external detector difficult.
While I shared much of this early enthusiasm for microfluidics, it was not until the early 2000’s that I started to see real utility for
microfluidics in LC, particularly to improve the usability of nano-scale chromatography. Rather than implement the full “Lab-on-a- Chip,” the best approach seemed to be replacing the typical nano-LC consumable package (i.e. trap column, analytical column, electrospray tip) with one integrated consumable device.
What particular aspects of ‘chip technology’ offered the possibilities of moving separation science forwards in your eyes? Were there any particular elements within the workflow of a typical lab that needed the advantages that this new technology could bring?
At the time we began working in microfluidics, interest in proteomics was on the rise which was best performed with nano- scale chromatography using fused silica tubing in order to get the sensitivity required. Our goal has been to retain the attributes of fused silica capillaries in a highly usable microfluidic device.
Proteomics was an area that seemed ripe for integrating all the fluidic components that make up a typical system: a trap column, analytical column, and electrospray tip onto one microfluidic platform or cartridge so the user wouldn’t need special skills to plumb together these fragile fused silica parts.
Was there such a thing as ‘first generation chips’ and what were the limitations restricting their usefulness in instrument design?
When we were developing our microfluidic platform, there were many “first generation chips” that had limitations. One thing we discovered is that at this nano-scale, surfaces become very important. The surface-to- volume ratio at this scale is significantly higher than at, say, the analytical scale (i.e. 2.1 mm I.D. columns). For a proteomics application, a digested protein sample contains a wide range of chemical species: basic, acidic, hydrophobic, hydrophilic peptides, and phosphopeptides, that will adhere to any metal-oxide surface. We learned quickly that we had to create inert surfaces to minimise any interactions of analytes with the surface. Early ceramic formulations we investigated were not inert enough and caused tailing for some basic and phosophopeptides. Through a combination of ceramic formulation and coating technologies, we engineered an inert and benign surface similar to that found in fused-silica tubing.
When did Waters first start to investigate the usefulness of the chips and consider how to integrate them into their instruments? How were they successfully interfaced?
In the early 2000’s we began working with Sandia Laboratories to develop an electrokinetic (EK) pump. By taking a bulky, reciprocating mechanical HPLC pump and replacing it with a small “solid state” disposable pump, we could take it to extremely high pressures. Essentially, an EK pump is a packed column where flow is
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