Microfluidic Liquid Chromatography

Microfluidics, or lab-on-a-chip systems, have been somewhat pigeonholed as being a technology for capillary electrophoresis, particularly with the success of the Agilent 2100 Bioanalyzer and Caliper Life Sciences’ LabChip products. However, the use of microfluidic technology in LC has grown rapidly during the past several years. Agilent introduced the first chip-based LC/MS system in 2005, which has since been widely adopted by protein chemists and proteomic researchers. In a microfluidic LC system, the chip combines the column and electrospray ionization (ESI) source for the MS. The LC chip is inserted into a separate module, which interfaces with the MS.

LC chips provide a technological advantage over traditional nanoflow HPLC systems by minimizing the plumbing requirements (fittings, connections, valves and tubing) between the column and the MS. They also enable the user to conserve sample, and they eliminate the labor of maintaining and cleaning the ESI spray tip.

Agilent recently introduced its second-generation HPLC-Chip, which includes a carbon ion implanted filter that extends the Chip’s life to more than 1,000 injections, depending on the application. In total, Agilent offers a dozen different HPLC-Chips for applications in peptide quantitation, biomarker discovery and small molecule analysis, among others (see page 9).

Waters recently entered the microfluidic LC market with the introduction of the TRIZAIC UPLC system with nanoTile technology (see IBO 5/31/08). While Agilent HPLC-Chips typically employ a 5 µm particle, Waters’s nanoTiles use sub-2 µm particle chemistries to provide efficient separation capabilities. Both Agilent’s HPLC-Chip and Waters’s TRIZAIC UPLC system are designed for use with the respective companies MS systems.

Like Agilent and Waters, Eksigent designed its microfluidic-based LC system to solve issues of dead volume, particularly when working with fused silica tubing. Eksigent’s cHiPLC-nanoflex system accommodates up to three microfluidic chips, which are more robust and easier to handle compared to traditional nano-LC columns, according to the company, and connect without introducing dead volume. With three chips, the cHiPLC-nanoflex allows for easy switching between direct injection, trap-loading, and dual column with direct injection experiments. The system can be used in combination with the company’s nanoLC systems and with any MS/nanospray source.

Microfluidic-based LC accounts for a small portion of the nano-LC market, but continues to gain momentum, due to demand from proteomics applications. The market is expected to post strong growth over the next few years, as methods and applications are developed and new chips are introduced. While Agilent has had sole reign in this market until recently, products by Waters and Eksigent now provide competition.

Microfluidic LC

at a Glance:

Leading Suppliers

• Agilent

• Waters

• Eksigent

Largest Markets

• Academia

• Government

• Pharmaceutical

Chip Cost

• $300–$500

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