US5228989A
Expired / Lapsed
US
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Perfusive chromatography
Assignee: Applied Biosystems LLC
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Filing: 1992-12-09
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Granted: 1993-07-20
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Expires: 2012-12-09
Abstract
Abstract Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.
Inventors
- 👤 Noubar B. Afeyan
- 👤 Fred E. Regnier
- 👤 Robert C. Dean, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 03:02
CPC Classifications
B; B01; B01J; B01J20/00; B01J20/281; B01J20/282; B01J20/285; B01D; B01D15/00; B01D15/08; B01D15/26; B01D15/34; B01J20/28; B01J20/28054; B01J20/28088; B01J20/28092; B01J20/28095; B01J2220/00; B01J2220/50; B01J2220/54; G; G01; G01N; G01N30/00; G01N30/02; G01N30/50; G01N30/52; G01N2030/524; G01N2030/528
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
95 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid defining interactive surface regions, having a mean diameter greater than 20 μm, and defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300 Å-700 Å for diffusive mass transport to said interactive surface regions, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 70.
Claim 2
Dependent Claim
95 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid defining interactive surface regions, having a mean diameter greater than 20 μm, and defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300 Å-700 Å for diffusive mass transport to said interactive surface regions, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 70.
Claim 3
Dependent Claim
114 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography at bed velocities less than about 1000 cm/hr, the particle comprising a rigid solid having a mean diameter and defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300 Å-700 Å for diffusive mass transport to solute interactive surface regions in fluid communication with the throughpores, said solute interactive surface regions being derivatized with a moiety other than polyethyleneimine, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 50.
Claim 4
Dependent Claim
114 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography at bed velocities less than about 1000 cm/hr, the particle comprising a rigid solid having a mean diameter and defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300 Å-700 Å for diffusive mass transport to solute interactive surface regions in fluid communication with the throughpores, said solute interactive surface regions being derivatized with a moiety other than polyethyleneimine, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 50.
Claim 5
Dependent Claim
91 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid other than divinylbenzene crosslinked polystyrene defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300Å-700 Å for diffusive mass transport to interactive surface regions in fluid communication with the throughpores, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 70.
Claim 6
Dependent Claim
91 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid other than divinylbenzene crosslinked polystyrene defining a plurality of throughpores sized for convective mass transport and a plurality of smaller pores having diameters within the range of 300Å-700 Å for diffusive mass transport to interactive surface regions in fluid communication with the throughpores, the ratio of the mean diameter of the particle to the mean diameter of the throughpores being less than 70.
Claim 7
Dependent Claim
26 words
The particle of claim 1, 2, or 3 comprising interadhered poron aggregates defining a plurality of subsets of throughpores and smaller pores of differing mean diameters.
Claim 8
Dependent Claim
31 words
The particle of claim 4 further defining branching pores communicating between the throughpores and smaller pores and having a mean diameter intermediate the mean diameters of the throughpores and smaller pores.
Claim 9
Dependent Claim
35 words
The particle of claim 1, 2, or 3 having a mean diameter greater than about 40 μm, the ratio of the mean particle diameter to the mean diameter of the throughpores being greater than 10.
Claim 10
Dependent Claim
15 words
The particle of claim 1 or 3 wherein said surface regions comprise an adhered coating.
Claim 11
Dependent Claim
32 words
The particle of claim 1, 2 or 3 wherein said solute interactive surface regions comprise a surface derivatized to produce an anionic exchange, cationic exchange, hydrophobic interaction, chelation, or affinity chromatography medium.
Claim 12
Dependent Claim
14 words
The particle of claim 2 or 3 having a diameter greater than 10 μm.
Claim 13
Dependent Claim
14 words
The particle of claim 2 or 3 having a diameter greater than 20 μm.
Claim 14
Dependent Claim
10 words
The particle of claim 1 or 2 comprising cross-linked polystyrene.
Claim 15
Dependent Claim
21 words
The particle of claims 1, 2, or 3 comprising a plurality of interadhered porons defining an interstitial space comprising said throughpores.
Claim 16
Dependent Claim
25 words
The particle of claim 1 or 3 which, when packed to form a matrix, perfuses at bed velocities less than about 1000 cm per hour.
Claim 17
Dependent Claim
137 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid having a diameter and defining a plurality of throughpores sized for convective mass transport, a plurality of smaller pores having diameters within the range of 300Å-700 Å for diffusive mass transport, and solute interactive surface regions in fluid communication with the throughpores, the ratio of the diameter of the particle to the mean diameter of the throughpores being less than 70, the interactive surface regions being derivatized to produce a cationic exchange, hydrophobic interaction, chelation, or affinity chromatography medium, the particle, when packed together with similar particles, being capable of forming a chromatography matrix characterized by the ability to achieve a Peclet number greater than 1.0 in said throughpores.
Claim 18
Dependent Claim
137 words
A particle defining a pore structure at least bimodal in its distribution that, when packed, produces a matrix suitable for perfusion chromatography, the particle comprising a rigid solid having a diameter and defining a plurality of throughpores sized for convective mass transport, a plurality of smaller pores having diameters within the range of 300Å-700 Å for diffusive mass transport, and solute interactive surface regions in fluid communication with the throughpores, the ratio of the diameter of the particle to the mean diameter of the throughpores being less than 70, the interactive surface regions being derivatized to produce a cationic exchange, hydrophobic interaction, chelation, or affinity chromatography medium, the particle, when packed together with similar particles, being capable of forming a chromatography matrix characterized by the ability to achieve a Peclet number greater than 1.0 in said throughpores.
Claim 19
Dependent Claim
11 words
The particle of claim 14 comprising a plurality of interadhered porons.
References Cited (Backward Citations)
US3488922A
Cited
US3862030A
Cited
US4102746A
Cited
US4070286A
Cited
US4186120A
Cited
US4070283A
Cited
US4131542A
Cited
US4384957A
Cited
US4512897A
Cited
US4477492A
Cited
US4496461A
Cited
US4604198A
Cited
US5037543A
Cited
US4986908A
Cited
US5019270A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-07-19 | 1997-01-18 | 1997-07-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-07-19 | 2001-01-18 | 2001-07-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-07-19 | 2005-01-18 | 2005-07-20 | $7700.00 | Window Closed / Lapsed |