Supercritical fluid chromatography (SFC) is used for small-molecule analysis and the separation of chiral compounds, enantiomers and other low-molecular-weight compounds. SFC differs from traditional LC in that its mobile phase is carbon dioxide, which necessitates a completely pressurized flow path. This pressure must be maintained with automated back-pressure regulators, and the units can be bulky and expensive. SFC uses detectors similar to HPLC’s but with specialized components suited to high-pressure conditions.

SFC is considered “green” due to the ability to recycle the primary mobile phase with over 90% efficiency. Along with high throughput, these are the primary attractive features of SFC. However, market traction in larger-scale applications has been slow because SFC has not developed a blockbuster application. The nutraceutical industry, particularly clinical research, could contribute to a shift in adoption.

Only a handful of manufacturers provide SFC units for purification. The somewhat-limited molecular-weight range eliminates much of SFC’s utility for biologics and other large-molecule applications, and the high upfront cost and specialized components hinder process-scale adoption.

Novasep is the most recognizable name for preparative-scale SFC and offers the Prochrom Supersep line. Each model is suited toward batch sizes from 1–50 g to 5,000–100,000 g. Novasep is also the primary vendor for truly process-scale SFC, with the largest version of the Prochrom offering a batch-size capacity larger than the majority of available systems. The Prochrom Supersep is targeted toward natural-extract solutions for APIs, the nutraceutical industry and chiral-compound separation for bulk pharmaceutical production.

For the preparative-scale SFC market, Waters offers the Prep 80q/200q and 350 systems. Each unit has an optimal column internal diameter of 19–50 mm, with corresponding flow rates of 80–300 g/min. The largest system, the SFC 350, has a typical eight-hour throughput of up to 100 g.

Jasco offers the PR-2088, a dedicated preparative SFC system for large-scale throughput, which is designed to bridge the gap between semipreparative- and process-scale SFC. It has a carbon dioxide-delivery rate of up to 120 mL/min., or up to 180 mL/min. with a modifier. With an autosampler, the PR-2088 can accommodate up to 40 mL. This model is Jasco’s largest-scale SFC unit, but the company also offers a semipreparative SFC “hybrid” unit. Smaller firms, such as PIC, offer mid-range preparative units with higher throughput than the semipreparative units.

The total annual market for preparative- and process-scale SFC is estimated to be nearly $40 million, with a mid-single-digit growth forecast, the majority of which is driven by preparative-scale units. Growth has a high ceiling if clinical trials involving some nutraceutical products, particularly omega-3s, begin to gain traction.

Preparative- and Process-Scale SFC at a Glance:

Leading Suppliers

• Waters

• Novasep

• Jasco

Largest Markets

• Pharmaceuticals

• CMOs

• Nutraceuticals

Instrument Cost

• $250,000–Several Million