TECHNICAL FIELD

This application generally relates to techniques for use with liquid chromatography, and more particularly to thermally insulating a liquid chromatography column.

BACKGROUND INFORMATION

Chromatography is a technique for separating compounds, such as those held in solution, where the compounds will exhibit different affinity for a separation medium in contact with the solution. As the solution flows through such an immobile separation medium, the compounds separate from one another. Common chromatographic separation instruments include liquid chromatography (LC) systems. Such LC systems are known and used for analyzing sample solutions that may include different chemical compounds. LC systems may operate at high pressures such as at 5,000 PSI and greater. A typical LC system includes a pump for pumping a liquid solution, an injector for injecting the sample into the liquid fluid stream, a chromatography column packed with packing material used as the separation medium and tubing for carrying the sample solution and liquid fluid from the injector to the chromatography column. The tubing may then be used to further transport the sample solution output from the LC column to a detector for analyzing the sample solution. The detector may be any suitable detector such as a mass spectrometer, a UV absorbance detector, an evaporative light scattering detector, and the like.

During operation of the LC system, a liquid solvent is pumped into the LC system at high pressure. The injector may be used to inject controlled volumes of a sample, either manually or automatically, into the system where the sample is carried with the liquid solvent in a fluid stream to the packed LC column where the sample may then be separated. Because each of the chemical compounds in the sample solution react in a different manner with the LC column packing material, the various chemical compounds flow through the packed LC column at different rates. The different chemical compounds in the sample solution separate from each other as the sample solution flows through the column. The separated chemical compounds as output from the LC column proceed to the detector where they may be further analyzed, for example, to determine physical characteristics of the compounds for purposes of identification and/or quantification.

SUMMARY OF THE INVENTION

In accordance with one aspect of the invention is an apparatus comprising: a chromatography column; and a plurality of temperature control units in thermal contact with the chromatography column. Each of the plurality of temperature control units may perform any of heating and cooling. A first of the plurality of temperature control units may be in thermal contact with an outlet of the chromatography column. The outlet may be at an end of the chromatography column out of which a mobile phase exits the chromatography column. A first of the plurality of temperature control units may be in thermal contact with an inlet of the chromatography column. The inlet may be at an end of the chromatography column into which a mobile phase flows. Each of the plurality of temperature control units may be in thermal contact with the chromatography column at a different axial position of the chromatography column. The axial position may be a location with respect to an axis of flow for mobile phase through the chromatography column. The first of the plurality of temperature control units may be used to heat the inlet of the chromatography column to a first temperature Tinand a second of the plurality of temperature control units may be used to heat an outlet of the chromatography column to a second temperature Tout. The outlet may be located at an end of the chromatography column opposite the inlet and may be an end out of which the mobile phase exits the chromatography column. Tinmay be less than Tout, and Tinand Toutmay both be greater than ambient temperature. The first of the plurality of temperature control units may be used to cool the inlet of the chromatography column to a first temperature Tinand a second of the plurality of temperature control units may be used to heat an outlet of the chromatography column to a second temperature Tout. The outlet may be located at an end of the chromatography column opposite the inlet and may be an end out of which the mobile phase exits the chromatography column. Tinmay be less than Toutand Tinmay be less than ambient temperature and Toutmay be greater than ambient temperature. An insulating layer may surround the chromatographic column. The insulating layer may be made from any of polystyrene foam, a polymer, polymethacrylate, silicone, urethane, polyolefins, polyamide, polysulfone, polyethyramide, polycarbonate, rubber, polyester, polyfluoroelastomers, polyethylene terephthalate, a ceramic, an aerogel, a fibrous material, methylcellulose and fiberglass. The insulating layer may be formed in an area between a jacket surrounding the chromatographic column and the chromatographic column. The insulating layer may comprise a vacuum. The vacuum may comprise an inert gas. The inert gas may be any of argon, xenon, krypton, carbon dioxide and sulfur hexafluoride. The vacuum may comprise atmospheric gas. The insulating layer and the jacket may be an integral component of the chromatographic column. The insulating layer may comprise a chamber including aerogel particles. A first of the plurality of control units may be located at an inlet of a fluid path through the chromatographic column. A second of the plurality of control units may be located at an outlet of the fluid path through the chromatographic column. A first temperature sensor may sense a first temperature at the inlet. A second temperature sensor may sense a second temperature at the outlet. A control means may control adjustment of the first control unit to set the first temperature at the inlet to a first desired value and may control adjustment of the second control unit to set the second temperature to a second desired value. The difference between the first desired value and the second desired value may represent a temperature difference, ΔTL, determined as

Δ⁢⁢TL=(1-α⁢⁢T_)⁢Δ⁢⁢Pρ⁢⁢Cp
where α is a thermal expansion coefficient of the mobile phase, T is the mean temperature of the mobile phase, ΔP is a pressure drop across the chromatographic column, Cpis a heat capacity of the mobile phase at constant pressure, andαTrepresents the average of a quantity αT, and ρ is a density of the mobile phase.

In accordance with another aspect of the invention is a method of performing liquid chromatography comprising: setting an inlet of a chromatography column to a first temperature using a first temperature control unit in thermal contact with said inlet; setting an outlet of the chromatography column to a second temperature using a second temperature control unit in thermal contact with said outlet, wherein the first temperature is less than the second temperature; and injecting a sample into a liquid stream that flows through the chromatography column after the inlet is set at the first temperature and the outlet is at the second temperature. The chromatography column may be thermally insulated. The method may include monitoring temperatures at the inlet and the outlet to determine when the inlet is at the first temperature and when the outlet is at the second temperature to thereby determine that the chromatography column is at steady state with respect to column temperature. Each of the first temperature control unit and the second temperature control unit may perform any of heating and cooling. The first temperature may be less than ambient temperature and the second temperature may be greater than ambient temperature. The first temperature and the second temperature may be greater than ambient temperature. The first temperature and the second temperature may be less than ambient temperature. An intermediate point may be located on the chromatography column between the inlet and the outlet and the method may include setting the intermediate point of the chromatography column to a third temperature using a third temperature control unit prior to injecting said sample, wherein the third temperature may be between the first temperature and the second temperature. The third temperature may be determined as a sum of the first temperature and an approximated value. The approximated value may be determined as a temperature offset proportional to a distance of the intermediate point from the inlet. The third temperature may be determined as an offset from the second temperature. The offset may be an approximated value determined as a temperature offset proportional to a distance of the intermediate point from the outlet. A difference between the first temperature and the second temperature ΔTLmay be determined based on

Δ⁢⁢TL=(1-α⁢⁢T_)⁢Δ⁢⁢Pρ⁢⁢Cp
where α is a thermal expansion coefficient of the mobile phase,Tis the mean temperature of the mobile phase, ΔP is a pressure drop across the chromatographic column, Cpis a heat capacity of the mobile phase at constant pressure, andαTrepresents mean value of quantity αT, and ρ is a density of the mobile phase.

