Chromatography system

• US 5,305,232 A
• Filed: 05/13/1992
• Issued: 04/19/1994
• Est. Priority Date: 05/13/1992
• Status: Expired due to Fees

• Current Assignee: University of Rochester
• Original Assignee: University of Rochester
• Inventors: Chimowitz, Eldred H., VanPuyvelde, Frank
• Primary Examiner(s): Black, Thomas G.
• Assistant Examiner(s): NGUYEN, TAN QUANG
• Application Number:
  US07/882,321
• Time in Patent Office: 706 Days
• Field of Search: 364/498, 364/499, 364/500, 55/67, 210/198.2, 210/386
• US Class Current: 702/32
• CPC Class Codes: B01D 15/40 using supercritical fluid as mobile phase or eluent
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/32 of pressure or speed G01N30/36 takes precedence
• CPC Class Codes: G01N 30/8658 Optimising operation parameters
• CPC Class Codes: G01N 30/8693 Models, e.g. prediction of retention times, method development and validation

Abstract

A system (method and apparatus) for optimizing the relationship between resolution and time in chromatograms, especially chromatograms obtained by supercritical fluids (CSF) chromatography. The pressure or temperature or fluid density of the solution caring the material under analysis is varied dynamically under computer control to provide an optimum capacity factor for a particular transporting fluid in a particular chromatographic system to obtain the resolution of interest in the shortest period of time.

Claims

1. The system for chromatographic analysis comprising:

(a) a column having a stationary substrate phase therein;

(b) said column also having a mobile transport phase having a capacity factor representing the ability of the mobile phase to transport a species under analysis through said column;

(c) detector means for dynamically measuring the time of migration of said species through said column;

(d) reporting means responsive to said dynamic migration time measurements for providing a chromatogram having data corresponding to said species; and

(e) computer means for processing said data for optimizing the relationship between resolution of the chromatogram provided by said reporting means and time;

said computer means comprising

(i) means responsive to said chromatogram for calculating the capacity factor for each of the species under analysis, and

(ii) means responsive to the capacity factor and physical parameters of the system including the column length and type of substrate and properties of the mobile transport phase selected from the group consisting of density, temperature and composition of the mobile phase.

2. The invention as set forth in claim 1 wherein said capacity factor changes over time and has a rate of change, and said computer means includes means responsive to the rate of change of the capacity factor.

3. The invention as set forth in claim 1, wherein said computer means includes means for calculating the minimum amount of time needed to obtain a desired resolution.

4. The invention as set forth in claim 1 wherein said computer means further comprises means for calculating the properties, selected from the group consisting of density and temperature needed to produce a desired resolution in a particular time period.

5. The invention as set forth in claim 1, wherein said computer means includes means responsive to an objective function which represents the chromatographic process, the objective function having (a) a time of analysis term and (b) a resolution term.

6. The invention as set forth in claim 5, wherein said computer means has means responsive to said objective function to calculate Lagrangian multiplier adjoint equations.

7. The invention as set forth in claim 5, wherein said computer means has means responsive to said objective function to calculate a plurality of outputs representing the derivative of a Hamiltonian equation with respect to a set of control variables.

8. The invention as set forth in claim 5, wherein said computer means has means responsive to the following objective function for optimizing the relationship between resolution of the reporting means and time;

##EQU26## where x_j =distance traveled in the column by the component j

L=length of the column

Δ

_j =distance between peaks

t_f =time of analysis

t₀ =initial time (0)

9. The invention as set forth in claim 1, wherein said mobile phase is a supercritical fluid.

10. The invention as set forth in claim 9, wherein said computer means has means for adjusting the capacity factor of the mobile phase by adjusting one or more of the parameters pressure, density and temperature within the chromatographic system.

11. The invention as set forth in claim 9, wherein said computer means has means for providing outputs corresponding to the pressure and temperature needed, for a given combination of substrate, species under analysis, and mobile phase supercritical fluid, to obtain a particular resolution in a particular time period.

12. The invention as set forth in claim 11, wherein said time period is a minimum time period.

13. A method of optimizing the relationship between resolution and time in a SCF chromatographic system having a column along which j analyte components are transported by a SFC mobile phase to provide a chromatogram having peaks separate by distances x_j (t) corresponding to the time for each of the j components to be transported to a downstream end of said column certain resolution in a optimally short period of time, comprising the steps of:

inputting an initial density profile ρ

(t) over time for the supercritical fluid mobile phase;

measuring x_j (t) from said peaks;

integrating the following modeling equation for the number of the analyte components j using the initial density profile;

##EQU27## where t=time

x=axial length down the column

m₀ =input mass flow rate to column

A=cross-sectional area of the bed

L=length of column

ρ

=mobile phase fluid density of the SCF

j=number of species being separated

kj=capacity factor (thermodynamic partition coefficient) for the j component

integrating the following Lagrangian multipliers backward in time over [t₀,t_f ] using the density profile (ρ

(t)) and the peaks x_j (t);

##EQU28## calculating a correction in density profile using the following equation;

##EQU29## and changing the density of said SCF in said column according to said correction.

14. The method as set forth in claim 13, further comprising the steps of:

using a one dimensional search technique to determine an optimal scaling factor ε

_opt ; and

calculating an improved density profile ρ

(t)^new using the following equation;

##EQU30##

15. The method as set forth in claim 14, further comprising:

determining the difference between ρ

(t) and ρ

(t)^new ; and

if said difference is greater than a chosen threshold value, recalculating optimum density by setting the initial density profile=ρ

(t)^new and repeating the steps set forth in claims 13 and 14.

16. A method for calculating an optimum temperature profile for a gaseous transport fluid which transports along a column of analyte components to be analyzed to obtain a chromatogram with peaks corresponding to the j components particular resolution in the shortest time in a gas chromatographic system having said column, comprising:

initializing the system by inputting an initial temperature profile T(t) over the time interval [t₀,t_f ] for the gas;

measuring the distance x_j (t) which corresponds to the time which it takes for each of the j components to travel along the column by the separation distance of the peaks;

integrating the following modeling equation for each component j using the initial temperature profile;

##EQU31## where t=time

x=axial length down the column

m₀ =input mass flow rate to column

A=cross-sectional area of the bed

L=length of column

ρ

=mobile phase fluid density of the SCF

j=number of species being separated

kj=capacity factor (thermodynamic partition coefficient) for the j component

integrating the following Lagrangian multipliers backward in time over [t₀,t_f ] using the temperature profile (T(t)) and the peaks x_j (t);

##EQU32## calculating a correction in temperature profile using the following equation;

##EQU33## and changing the temperature of the gas in the column in accordance with the correction.

17. The method as set forth in claim 16, further comprising the steps of:

using a one dimensional search technique to determine the optimal scaling factor ε

_opt ; and

calculating a new temperature profile using the following equation;

##EQU34##

18. The method as set forth in claim 17, further comprising:

determining the difference between T(t) and T(t)^new ; and

if said difference is greater than a chosen threshold value, regulating optimum temperature profile by setting the initial density profile=T(t)^new and repeating the steps set forth in claims 16 and 71.

19. A method for calculating an optimum composition profile of a liquid transport fluid to obtain a particular resolution in the shortest time in a liquid chromatographic system which provides a chromatogram having a plurality of spaced peaks corresponding to a plurality j of analyte components which are transported along a column, the peaks being separated by distances xj(t) which correspond to the time it takes for each of the j components to be transported along the column, comprising:

initializing the system with an initial composition profile c(t) over time for the liquid transport fluid;

measuring xj(t) from the peaks;

integrating the following modeling equation for each component j using the initial composition profile;

##EQU35## where t=time

x=axial length down the column

m₀ =input mass flow rate to column

A=cross-sectional area of the bed

L=length of column

ρ

=mobile phase fluid density of the SCF

j=number of species being separated

kj=capacity factor (thermodynamic partition coefficient) for the j component

integrating the following Langrangian multipliers backward in time over [t₀,t_f ] using the composition profile (c(t)) and the peaks x_j (t);

##EQU36## calculating a correction composition profile using the following equation;

##EQU37## and changing the composition of said liquid in accordance with said correction.

20. The method as set forth in claim 19, further comprising the steps of:

using a one dimensional search technique to determine the optimal scaling factor ε

_opt ; and

calculating a new composition profile c(t)^new using the following equation;

##EQU38##

21. The method as set forth in claim 20, further comprising:

determining the difference between c(t) and c(t)^new ; and

if said difference is greater than a chosen threshold value, recalculating optimum composition profile by setting the initial composition profile=c(t)^new and repeating the steps set forth in claims 19 and 20.