Mobile phase controller for supercritical fluid chromatography systems

1. A method of controlling mobile phase density or pressure in a carbon dioxide based separation system, comprising:

measuring a first mobile phase density or pressure at a first sensor located upstream of a chromatography column, and a second mobile phase density or pressure at a second sensor located downstream of the chromatography column to generate a first set of measurements;

calculating an average mobile phase density or pressure in the system from the first set of measurements using a controller in communication with the first and second sensors;

comparing the average mobile phase density or pressure with a pre-determined average mobile phase density or pressure; and

adjusting at least one system component or parameter to achieve the pre-determined average mobile phase density or pressure.

2. The method of claim 1 , further comprising

transmitting the first set of measurements to the controller to calculate the average mobile phase density or pressure in the system.

3. The method of claim 1 , wherein the first mobile phase density or pressure and the second mobile phase density or pressure are measured simultaneously.

4. The method of claim 1 , wherein the at least one system component or parameter adjusted is a back pressure regulator.

5. The method of claim 4 , wherein the back pressure regulator is adjusted to a produce a higher pressure in the system if the average mobile phase density or pressure value is lower than the pre-determined average mobile phase density or pressure, and wherein the back pressure regulator is adjusted to produce a lower pressure in the system if the average mobile phase density or pressure value is higher than the pre-determined average mobile phase density or pressure.

6. The method of claim 1 , wherein the mobile phase density or pressure in the system is at equilibrium when the at least one system component or parameter is adjusted.

7. The method of claim 1 , wherein the mobile phase density or pressure in the system is not at equilibrium when the at least one system component or parameter is adjusted.

8. The method of claim 1 , further comprising repeating the determining, comparing and adjusting steps until the pre-determined average mobile phase density or pressure is achieved.

9. The method of claim 8 , wherein the time between consecutive adjustments of the at least one system component or parameter is less than about 10 seconds.

10. The method of claim 1 , wherein the first sensor is a first pressure sensor capable of measuring a first mobile phase pressure in the system and the second sensor is a second pressure sensor capable of measuring a second mobile phase pressure in the system.

11. The method of claim 10 , wherein the first pressure sensor is contained in or connected to a pump.

12. The method of claim 10 , wherein the second pressure sensor is contained in or connected to a back pressure regulator.

13. The method of claim 12 , wherein the first sensor is a first density sensor capable of measuring a first mobile phase density in the system and the second sensor is a second density sensor capable of measuring a second mobile phase density in the system.

14. The method of claim 1 , wherein determining the average mobile phase density or pressure includes determining the average mobile phase density or pressure across one or more components of the carbon dioxide based separation system.

15. The method of claim 1 , wherein determining the average mobile phase density or pressure includes determining the average mobile phase density or pressure across the carbon dioxide based separation system at initial gradient conditions and final gradient conditions.

16. The method of claim 1 , wherein determining the average mobile phase density or pressure includes determining the average mobile phase density or pressure across the carbon dioxide based separation system over a specified time period.

17. A carbon dioxide based separation system comprising:

a pump;

a column located downstream of the pump;

at least one back pressure regulator located downstream of the column,

a first sensor located upstream of the column, wherein the first sensor is capable of measuring a first mobile phase density or pressure in the system;

a second sensor located downstream of the column, wherein the second sensor is capable of measuring a second mobile phase density or pressure in the system;

a controller in signal communication with the first and second sensors; and

a set of instructions utilized by the controller, wherein the controller is capable of averaging the first and the second mobile phase density or pressure measurements to determine an average mobile phase density or pressure value and adjusting at least one system component or parameter to achieve a pre-determined average mobile phase density or pressure in the system in response to the average mobile phase density or pressure value;

the carbon dioxide based separation system being configured to perform the method of claim 1 .