US 11,406,915 B2Granted

Multicapillary packing chromatography method

AssigneeSeparative

InventorFrancois Parmentier

Life of this patent

Estimating the term…

Abstract

Chromatography method in which a gaseous, liquid or supercritical mobile phase containing species to be separated is circulated through a packing, said packing being characterized in that: —it comprises a plurality of capillary ducts extending in the packing between an upstream face through which the mobile phase enters the packing and a downstream face through which the mobile phase leaves the packing—the material of the walls comprises a first population of connected pores, providing passages from one duct to the next enabling molecular diffusion to take place between adjacent ducts, pores having a mean diameter (dpore) of greater than 2 times the molecular diameter of at least one species to be separated—the diameter of the ducts is less than 50 μm.

Claims13

Dependent claims

A chromatography method in which a gaseous mobile phase is circulated, containing species to be separated through a packing comprising a stationary phase, wherein

the packing includes a plurality of capillary conduits extending in the packing between an upstream face through which the mobile phase penetrates into the packing and a downstream face through which the mobile phase emerges from the packing,
the material of the walls of said conduits includes a network of connected pores, said pores forming passages from one conduit to the other allowing molecular diffusion to be operated between adjacent conduits, said pores having an average diameter greater than a mean free path of the molecules of the species to be separated,
the average diameter of the conduits is less than 50 μm,
wherein:
the method comprises computing a relative dispersion height ratio of a theoretical plate height of the packing due to inhomogeneities of the packing over a total theoretical plate height of the packing and adjusting at least one operative parameter of the chromatography or at least one morphologic feature of the packing so that said relative dispersion height ratio is less than 0.66,
the species to be separated have a molecular radius Rh in the elution solvent, a molecular diffusivity Do in the elution solvent, a molecular diffusivity Ds in or on the stationary phase, a sharing coefficient K between the stationary phase and the elution solvent, a retention factor k′ in the chromatographic column defined by the formula:
k
′
=
t
R
-
t
0
t
0
,
wherein to is a retention time of a non-retained compound and tR is a retention time of a retained compound, and
the packing includes conduits of an average diameter dc separated with walls of an average thickness de for which the irregularity is defined by a standard deviation of the diameter dc reduced to its average SigmaD, by a standard deviation of the thickness de reduced to its average SigmaE, and by a standard deviation of the length of the conduits reduced to its average SigmaL,
the constitutive porous material of the walls has a porous volume fraction P, a volume fraction of stationary phase fVolStat or a specific adsorption surface area S, a tortuosity T=1−0.8*ln(P), and the network of connected pores has a diameter dpore,
the mobile phase flows with an average velocity vc in the conduits and
the method comprises computing the theoretical plate height (Hdisp) due to the inhomogeneities of the packing based on the relationship:
⁢
H
disp
=
0.778
⋆
v
0
⋆
(
FKD
⋆
SigmaD
2
+
FKE
⋆
SigmaE
2
+
FKL
⋆
SigmaL
2
)
⋆
(
d
c
+
d
e
)
2
FDiff
⋆
FDil
⋆
(
1
+
k
′
)
⋆
2
⁢
wherein
⁢
:
⁢
⁢
v
0
⁢
⁢
⁢
is
⁢
⁢
the
⁢
⁢
elution
⁢
⁢
velocity
⁢
⁢
of
⁢
⁢
a
⁢
⁢
non
⁢
⁢
-
⁢
retained
⁢
⁢
compound
⁢
⁢
by
⁢
⁢
the
⁢
⁢
stationary
⁢
⁢
phase
⁢
⁢
FKD
=
(
2
+
3
⋆
k
′
1
+
k
′
)
2
⁢
FKE
=
(
k
0
⋆
PB
(
1
+
k
0
)
)
2
⁢
FKL
=
4
⁢
k
0
=
(
f
VolStat
⋆
K
+
P
)
⋆
d
e
⋆
(
2
⋆
d
c
+
d
e
)
d
c
2
⁢
PB
=
(
2
⋆
d
c
+
2
⋆
d
e
)
(
2
⋆
d
c
+
d
e
)
⁢
Fdiff
=
d
c
+
d
e
d
c
DC
+
d
e
DE
⁢
DC
=
d
c
⋆
d
c
⋆
D
0
+
[
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
-
d
c
⋆
d
c
]
⋆
DE
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
DE
=
D
0
⋆
P
⋆
C
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
+
D
s
⋆
f
VolStat
⋆
C
⋆
K
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
⁢
FDil
=
d
c
2
(
d
c
2
+
(
(
d
c
+
d
e
)
2
-
d
c
2
)
⋆
(
P
+
f
VolSat
⋆
K
)
)
C is a correction coefficient of the diffusivity in a free medium related to the size of the pores and to the diameter of the molecules to be separated.

358 more elements

A chromatography method comprising:

selecting a mobile phase containing at least one species to be separated;
selecting a packing comprising a stationary phase, wherein
the packing includes a plurality of capillary conduits extending in the packing between an upstream face through which the mobile phase penetrates into the packing and a downstream face through which the mobile phase emerges from the packing,
the material of the walls of said conduits includes a network of connected pores, said pores forming passages from one conduit to the other allowing molecular diffusion to be operated between adjacent conduits, said pores having an average diameter greater than twice the molecular diameter of the at least one species to be separated, and
the average diameter of the conduits is less than 50 μm;
and
circulating the mobile phase in gas or liquid state through the selected packing,
wherein:
the method comprises computing a relative dispersion height ratio of a theoretical plate height of the packing due to inhomogeneities of the packing over a total theoretical plate height of the packing and adjusting at least one operative parameter of the chromatography or at least one morphologic feature of the packing so that that said relative dispersion height ratio is less than 0.66,
the species to be separated have a molecular radius Rh in the elution solvent, a molecular diffusivity D0 in the elution solvent, a molecular diffusivity Ds in or on the stationary phase, a sharing coefficient K between the stationary phase and the elution solvent, a retention factor k′ in the chromatographic column defined by the formula:
k
′
=
t
R
-
t
0
t
0
,
wherein to is a retention time of a non-retained compound and tR is a retention time of a retained compound, and
the packing includes conduits of an average diameter dc separated with walls of an average thickness de for which the irregularity is defined by a standard deviation of the diameter dc reduced to its average SigmaD, by a standard deviation of the thickness de reduced to its average SigmaE and by a standard deviation of the length of the conduits reduced to its average SigmaL,
the constitutive porous material of the walls has a porous volume fraction P, a volume fraction of stationary phase fVolStat or a specific adsorption surface area S, a tortuosity T=1−0.8*ln(P), and the network of connected pores has a diameter dpore,
the mobile phase flows with an average velocity vc in the conduits and
the method comprises computing the theoretical plate height (Hdisp) due to the inhomogeneities of the packing based on the relationship:
⁢
H
disp
=
0.778
⋆
v
0
⋆
(
FKD
⋆
SigmaD
2
+
FKE
⋆
SigmaE
2
+
FKL
⋆
SigmaL
2
)
⋆
(
d
c
+
d
e
)
2
FDiff
⋆
FDil
⋆
(
1
+
k
′
)
⋆
2
⁢
wherein
⁢
:
⁢
⁢
v
0
⁢
⁢
⁢
is
⁢
⁢
the
⁢
⁢
elution
⁢
⁢
velocity
⁢
⁢
of
⁢
⁢
a
⁢
⁢
non
⁢
⁢
-
⁢
retained
⁢
⁢
compound
⁢
⁢
by
⁢
⁢
the
⁢
⁢
stationary
⁢
⁢
phase
⁢
⁢
FKD
=
(
2
+
3
⋆
k
′
1
+
k
′
)
2
⁢
FKE
=
(
k
0
⋆
PB
(
1
+
k
0
)
)
2
⁢
FKL
=
4
⁢
k
0
=
(
f
VolStat
⋆
K
+
P
)
⋆
d
e
⋆
(
2
⋆
d
c
+
d
e
)
d
c
2
⁢
PB
=
(
2
⋆
d
c
+
2
⋆
d
e
)
(
2
⋆
d
c
+
d
e
)
⁢
Fdiff
=
d
c
+
d
e
d
c
DC
+
d
e
DE
⁢
DC
=
d
c
⋆
d
c
⋆
D
0
+
[
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
-
d
c
⋆
d
c
]
⋆
DE
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
DE
=
D
0
⋆
P
⋆
C
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
+
D
s
⋆
f
VolStat
⋆
C
⋆
K
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
⁢
FDil
=
d
c
2
(
d
c
2
+
(
(
d
c
+
d
e
)
2
-
d
c
2
)
⋆
(
P
+
f
VolSat
⋆
K
)
)
C is a correction coefficient of the diffusivity in a free medium related to the size of the pores and to the diameter of the molecules to be separated.

362 more elements

A chromatography method in which a liquid mobile phase is circulated, containing species to be separated through a packing comprising a stationary phase, wherein

the packing includes a plurality of capillary conduits extending in the packing between an upstream face through which the mobile phase penetrates into the packing and a downstream face through which the mobile phase emerges from the packing,
the material of the walls of said conduits includes a network of connected pores, said pores forming passages from one conduit to the other allowing molecular diffusion to be operated between adjacent conduits, said pores having an average diameter twice the molecular diameter of at least one species to be separated, said average diameter being:
(i) comprised between 4 and 30 nm for molecules of the species to be separated having a molecular weight comprised between 0 and 1,000 g/mole,
(ii) comprised between 10 and 100 nm for molecules of the species to be separated having a molecular weight of 10,000 g/mole, or
(iii) comprised between 30 and 300 nm for molecules of the species to be separated having a molecular weight of 100,000 g/mole,
the average diameter of the conduits is less than 50 μm,
wherein:
the method comprises computing a relative dispersion height ratio of a theoretical plate height of the packing due to inhomogeneities of the packing over a total theoretical plate height of the packing and adjusting at least one operative parameter of the chromatography or at least one morphologic feature of the packing so that said relative dispersion height ratio is less than 0.66,
the species to be separated have a molecular radius Rh in the elution solvent, a molecular diffusivity D0 in the elution solvent, a molecular diffusivity Ds in or on the stationary phase, a sharing coefficient K between the stationary phase and the elution solvent, a retention factor k′ in the chromatographic column defined by the formula:
k
′
=
t
R
-
t
0
t
0
,
wherein to is a retention time of a non-retained compound and tR is a retention time of a retained compound, and
the packing includes conduits of an average diameter dc separated with walls of an average thickness de for which the irregularity is defined by a standard deviation of the diameter dc reduced to its average SigmaD, by a standard deviation of the thickness de reduced to its average SigmaE and by a standard deviation of the length of the conduits reduced to its average SigmaL,
the constitutive porous material of the walls has a porous volume fraction P, a volume fraction of stationary phase fVolStat or a specific adsorption surface area S, a tortuosity T=1−0.8*ln(P), and the network of connected pores has a diameter dpore,
the mobile phase flows with an average velocity vc in the conduits and
the method comprises computing the theoretical plate height (Hdisp) due to the inhomogeneities of the packing based on the relationship:
⁢
H
disp
=
0.778
⋆
v
0
⋆
(
FKD
⋆
SigmaD
2
+
FKE
⋆
SigmaE
2
+
FKL
⋆
SigmaL
2
)
⋆
(
d
c
+
d
e
)
2
FDiff
⋆
FDil
⋆
(
1
+
k
′
)
⋆
2
⁢
wherein
⁢
:
⁢
⁢
v
0
⁢
⁢
⁢
is
⁢
⁢
the
⁢
⁢
elution
⁢
⁢
velocity
⁢
⁢
of
⁢
⁢
a
⁢
⁢
non
⁢
⁢
-
⁢
retained
⁢
⁢
compound
⁢
⁢
by
⁢
⁢
the
⁢
⁢
stationary
⁢
⁢
phase
⁢
⁢
FKD
=
(
2
+
3
⋆
k
′
1
+
k
′
)
2
⁢
FKE
=
(
k
0
⋆
PB
(
1
+
k
0
)
)
2
⁢
FKL
=
4
⁢
k
0
=
(
f
VolStat
⋆
K
+
P
)
⋆
d
e
⋆
(
2
⋆
d
c
+
d
e
)
d
c
2
⁢
PB
=
(
2
⋆
d
c
+
2
⋆
d
e
)
(
2
⋆
d
c
+
d
e
)
⁢
Fdiff
=
d
c
+
d
e
d
c
DC
+
d
e
DE
⁢
DC
=
d
c
⋆
d
c
⋆
D
0
+
[
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
-
d
c
⋆
d
c
]
⋆
DE
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
DE
=
D
0
⋆
P
⋆
C
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
+
D
s
⋆
f
VolStat
⋆
C
⋆
K
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
⁢
FDil
=
d
c
2
(
d
c
2
+
(
(
d
c
+
d
e
)
2
-
d
c
2
)
⋆
(
P
+
f
VolSat
⋆
K
)
)
C is a correction coefficient of the diffusivity in a free medium related to the size of the pores and to the diameter of the molecules to be separated.

361 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/514,918Filed 29 Sep 2015
Priority: FR 145917629 Sep 2014
Published: US 2017/0259190 A114 Sep 2017
Granted: 9 Aug 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

B01D 15/22
Characterised by constructional or operational features: relating to the construction of the column
B01D 15/40
Characterised by the separation mechanism: using supercritical fluid as mobile phase or eluent
B01D 53/025
By adsorption, e.g. preparative gas chromatography: with wetted adsorbents; Chromatography
B01J 20/103
Comprising silica or silicate: comprising silica

Family

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From the US filing history. Foreign family members aren’t listed.

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Abstract

A chromatography method in which a gaseous mobile phase is circulated, containing species to be separated through a packing comprising a stationary phase, wherein

the packing includes a plurality of capillary conduits extending in the packing between an upstream face through which the mobile phase penetrates into the packing and a downstream face through which the mobile phase emerges from the packing,
the material of the walls of said conduits includes a network of connected pores, said pores forming passages from one conduit to the other allowing molecular diffusion to be operated between adjacent conduits, said pores having an average diameter greater than a mean free path of the molecules of the species to be separated,
the average diameter of the conduits is less than 50 μm,
wherein:
the method comprises computing a relative dispersion height ratio of a theoretical plate height of the packing due to inhomogeneities of the packing over a total theoretical plate height of the packing and adjusting at least one operative parameter of the chromatography or at least one morphologic feature of the packing so that said relative dispersion height ratio is less than 0.66,
the species to be separated have a molecular radius Rh in the elution solvent, a molecular diffusivity Do in the elution solvent, a molecular diffusivity Ds in or on the stationary phase, a sharing coefficient K between the stationary phase and the elution solvent, a retention factor k′ in the chromatographic column defined by the formula:
k
′
=
t
R
-
t
0
t
0
,
wherein to is a retention time of a non-retained compound and tR is a retention time of a retained compound, and
the packing includes conduits of an average diameter dc separated with walls of an average thickness de for which the irregularity is defined by a standard deviation of the diameter dc reduced to its average SigmaD, by a standard deviation of the thickness de reduced to its average SigmaE, and by a standard deviation of the length of the conduits reduced to its average SigmaL,
the constitutive porous material of the walls has a porous volume fraction P, a volume fraction of stationary phase fVolStat or a specific adsorption surface area S, a tortuosity T=1−0.8*ln(P), and the network of connected pores has a diameter dpore,
the mobile phase flows with an average velocity vc in the conduits and
the method comprises computing the theoretical plate height (Hdisp) due to the inhomogeneities of the packing based on the relationship:
⁢
H
disp
=
0.778
⋆
v
0
⋆
(
FKD
⋆
SigmaD
2
+
FKE
⋆
SigmaE
2
+
FKL
⋆
SigmaL
2
)
⋆
(
d
c
+
d
e
)
2
FDiff
⋆
FDil
⋆
(
1
+
k
′
)
⋆
2
⁢
wherein
⁢
:
⁢
⁢
v
0
⁢
⁢
⁢
is
⁢
⁢
the
⁢
⁢
elution
⁢
⁢
velocity
⁢
⁢
of
⁢
⁢
a
⁢
⁢
non
⁢
⁢
-
⁢
retained
⁢
⁢
compound
⁢
⁢
by
⁢
⁢
the
⁢
⁢
stationary
⁢
⁢
phase
⁢
⁢
FKD
=
(
2
+
3
⋆
k
′
1
+
k
′
)
2
⁢
FKE
=
(
k
0
⋆
PB
(
1
+
k
0
)
)
2
⁢
FKL
=
4
⁢
k
0
=
(
f
VolStat
⋆
K
+
P
)
⋆
d
e
⋆
(
2
⋆
d
c
+
d
e
)
d
c
2
⁢
PB
=
(
2
⋆
d
c
+
2
⋆
d
e
)
(
2
⋆
d
c
+
d
e
)
⁢
Fdiff
=
d
c
+
d
e
d
c
DC
+
d
e
DE
⁢
DC
=
d
c
⋆
d
c
⋆
D
0
+
[
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
-
d
c
⋆
d
c
]
⋆
DE
(
d
c
+
d
e
)
⋆
(
d
c
+
d
e
)
DE
=
D
0
⋆
P
⋆
C
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
+
D
s
⋆
f
VolStat
⋆
C
⋆
K
⋆
(
P
+
f
VolStat
)
T
⋆
(
P
+
f
VolStat
⋆
K
)
⁢
FDil
=
d
c
2
(
d
c
2
+
(
(
d
c
+
d
e
)
2
-
d
c
2
)
⋆
(
P
+
f
VolSat
⋆
K
)
)
C is a correction coefficient of the diffusivity in a free medium related to the size of the pores and to the diameter of the molecules to be separated.

358 more elements

Facts

Application

15/514,918Filed 29 Sep 2015

Priority

FR 145917629 Sep 2014

Published

US 2017/0259190 A114 Sep 2017

Granted

9 Aug 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

B01D 15/22
Characterised by constructional or operational features: relating to the construction of the column
B01D 15/40
Characterised by the separation mechanism: using supercritical fluid as mobile phase or eluent
B01D 53/025
By adsorption, e.g. preparative gas chromatography: with wetted adsorbents; Chromatography
B01J 20/103
Comprising silica or silicate: comprising silica