US5043260A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Perfusion device with hepatocytes
Assignee: RHODE ISLAND HOSPITAL PROVIDENCE RHODE ISLAND A RHODE ISLAND CORP
•
Filing: 1987-11-02
•
Granted: 1991-08-27
•
Expires: 2007-11-02
Abstract
Abstract A perfusion device to grow and maintain hepatocytes including a chamber having a perfusion inlet and a perfusion outlet, a semipermeable membrane in the chamber defining separate perfusion and hepatocyte compartments, and hepatocytes in the hepatocyte compartment attached via oligosaccharide-lectin recognition linkage to a biopolymer support in the hepatocyte compartment.
Inventors
- 👤 Hugo O. Jauregui
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 12:03
CPC Classifications
A; A61; A61F; A61F2/00; A61F2/02; A61F2/022; A61M; A61M1/00; A61M1/14; A61M1/16; A61M1/1621; A61M1/1623; A61M1/1627; A61M1/34; A61M1/3472; A61M1/3475; A61M1/3486; A61M1/3489; C; C12; C12M; C12M25/00; C12M25/10; C12M29/00; C12M29/10; C12M29/16
Claims Analysis
Total Claims: 55
Claim 1
Independent Claim
120 words
An article of manufacture to grow and maintain hepatocytes comprising: a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 2
Dependent Claim
120 words
An article of manufacture to grow and maintain hepatocytes comprising: a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 3
Dependent Claim
13 words
The article of claim 1, wherein said first hepatocytes have cytochrome P450 activity.
Claim 4
Dependent Claim
27 words
The article of claim 1, wherein said membrane means comprises a first set of porous hollow fibers, the interiors of said hollow fibers defining said perfusion compartment.
Claim 5
Dependent Claim
29 words
The article of claim 1, wherein said at least one of a first oligosaccharide and a first lectin is a first lectin and is fixedly attached by covalent bonding.
Claim 6
Dependent Claim
29 words
The article of claim 1, wherein said at least one of a first oligosaccharide and a first lectin is a first oligosaccharide and is fixedly attached by covalent bonding.
Claim 7
Dependent Claim
36 words
The article of claim 4, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanavalin A.
Claim 8
Dependent Claim
13 words
The article of claim 6, wherein said first lectin is Lens culinaris agglutinin.
Claim 9
Dependent Claim
13 words
The article of claim 6, wherein said first lectin is wheat germ agglutinin.
Claim 10
Dependent Claim
17 words
The article of claim 3, wherein said first set of hollow fibers are made of polyacrylic polyurethane.
Claim 11
Dependent Claim
68 words
The article of claim 3, wherein said chamber further comprises a waste inlet means and a waste outlet means and wherein said membrane means further comprises a second set of hollow fibers, wherein the interiors of said second set of hollow fibers define a separate waste compartment adjacent said hepatocyte compartment, said waste inlet means and said waste outlet means being in fluid communication with said waste compartment.
Claim 12
Dependent Claim
77 words
The article of claim 10, wherein said at least one of a first oligosaccharide and a first lectin is attached to the exterior of said first set of hollow fibers and further comprising, at least one of a second oligosaccharide and a second lectin fixedly attached to the exterior of said second set of hollow fibers and second hepatocytes attached to said at least one of a second oligosaccharide and a second lectin via oligosaccharide-lectin recognition linkages.
Claim 13
Dependent Claim
37 words
The article of claim 11, wherein said at least one of a first oligosaccharide and a first lectin is a first lectin, said first lectin recognizing sugars located predominantly at the sinusoidal domain of said first hepatocytes.
Claim 14
Dependent Claim
37 words
The article of claim 12, wherein said at least one of a second oligosaccharide and a second lectin is a second lectin, said second lectin recognizing sugars located predominantly at the bile domain of said second hepatocytes.
Claim 15
Dependent Claim
24 words
The article of claim 13, wherein said first lectin is a member of the group consisting of Lens culinaris agglutinin or Phaseolus vulgaris agglutinin.
Claim 16
Dependent Claim
13 words
The article of claim 14, wherein said second lectin is wheat germ agglutinin.
Claim 17
Dependent Claim
17 words
The article of claim 3, 6, 9 or 11, wherein said first hepatocytes have cytochrome P450 activity.
Claim 18
Dependent Claim
27 words
The article of claim 1, further comprising tubes for connection to a patient, said tubes being connected to said perfusion inlet means and said perfusion outlet means.
Claim 19
Dependent Claim
20 words
The article of claim 17, further comprising returning means for returning some products produced by said hepatocytes to the patient.
Claim 20
Dependent Claim
19 words
The article of claim 18, further comprising treating means for treating the products prior to return to the patient.
Claim 21
Dependent Claim
16 words
The article of claim 1, further comprising flushing means for flushing nutrients through said perfusion compartment.
Claim 22
Dependent Claim
17 words
The article of claim 1, wherein said membrane means has molecular weight cutoffs of 40,000 to 250,000.
Claim 23
Dependent Claim
24 words
The article of claim 1, wherein said membrane means is constructed so as to prevent passage of white and red cells and immunoglobulins therethrough.
Claim 24
Dependent Claim
135 words
An article of manufacture to grow and maintain hepatocytes comprising: a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, a biocompatible polymer support means in said hepatocyte compartment, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and first lectin via oligosaccharide-lectin recognition linkages.
Claim 25
Dependent Claim
135 words
An article of manufacture to grow and maintain hepatocytes comprising: a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, a biocompatible polymer support means in said hepatocyte compartment, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and first lectin via oligosaccharide-lectin recognition linkages.
Claim 26
Dependent Claim
13 words
The article of claim 23, wherein said first hepatocytes have cytochrome P450 activity.
Claim 27
Dependent Claim
29 words
The article of claim 23, wherein said at least one of a first oligosaccharide and a first lectin is a first lectin and is fixedly attached by covalent bonding.
Claim 28
Dependent Claim
36 words
The article of claim 25, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanavalin A.
Claim 29
Independent Claim
124 words
A method of making a perfusion device for growing and maintaining hepatocytes comprising: providing a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, fixedly attaching at least one of a first oligosaccharide and a first lectin to a portion of said membrane means facing said hepatocyte compartment, and attaching first hepatocytes to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 30
Independent Claim
124 words
A method of making a perfusion device for growing and maintaining hepatocytes comprising: providing a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, fixedly attaching at least one of a first oligosaccharide and a first lectin to a portion of said membrane means facing said hepatocyte compartment, and attaching first hepatocytes to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 31
Dependent Claim
13 words
The method of claim 27, wherein said first hepatocytes have cytochrome P450 activity.
Claim 32
Dependent Claim
27 words
The method of claim 27, wherein said membrane means comprises a first set of porous hollow fibers, the interiors of said hollow fibers defining said perfusion compartment.
Claim 33
Dependent Claim
32 words
The method of claim 29, wherein said at least one of a first oligosaccharide and a first lectin is a first lectin and said first lectin is fixedly attached by covalent bonding.
Claim 34
Dependent Claim
36 words
The method of claim 30, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanavalin A.
Claim 35
Dependent Claim
24 words
The method of claim 30, wherein said first hepatocytes are attached by injecting a seeding medium including said first hepatocytes into said hepatocyte compartment.
Claim 36
Dependent Claim
36 words
The method of claim 32, which further comprises waiting a period of time after said injecting to allow said first hepatocytes to attach to said first lectin, and then flushing said medium from said hepatocyte compartment.
Claim 37
Dependent Claim
23 words
The method of claim 33, further comprising flushing nutrients through said perfusion compartment after attaching said first hepatocytes to maintain said first hepatocytes.
Claim 38
Independent Claim
141 words
A method of making a perfusion device for growing and maintaining hepatocytes comprising: providing a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, a biocompatible polymer support means in said hepatocyte compartment, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, fixedly attaching at least one of a first oligosaccharide and a first lectin to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and attaching first hepatocytes to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 39
Independent Claim
141 words
A method of making a perfusion device for growing and maintaining hepatocytes comprising: providing a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, a biocompatible polymer support means in said hepatocyte compartment, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, fixedly attaching at least one of a first oligosaccharide and a first lectin to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and attaching first hepatocytes to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages.
Claim 40
Dependent Claim
13 words
The method of claim 35, wherein said first hepatocytes have cytochrome P450 activity.
Claim 41
Dependent Claim
32 words
The method of claim 35, wherein said at least one of a first oligosaccharide and a first lectin is a first lectin and said first lectin is fixedly attached by covalent binding.
Claim 42
Dependent Claim
36 words
The method of claim 37, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanavalin A.
Claim 43
Independent Claim
141 words
A method of using a hepatocyte perfusion device comprising: providing a perfusion device including a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages, and causing perfusion liquid to flush through said inlet means, said perfusion compartment, and said outlet means.
Claim 44
Independent Claim
141 words
A method of using a hepatocyte perfusion device comprising: providing a perfusion device including a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages, and causing perfusion liquid to flush through said inlet means, said perfusion compartment, and said outlet means.
Claim 45
Dependent Claim
13 words
The method of claim 39, wherein said first hepatocytes have cytochrome P450 activity.
Claim 46
Dependent Claim
27 words
The method of claim 39, wherein said membrane means comprises a first set of porous hollow fibers, the interiors of said hollow fibers defining said perfusion compartment.
Claim 47
Dependent Claim
36 words
The method of claim 41, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanvalin A.
Claim 48
Dependent Claim
24 words
The method of claim 40, wherein said perfusion liquid comprises blood, and tubes connect a patient to said perfusion inlet means and outlet means.
Claim 49
Dependent Claim
18 words
The method of claim 43, further comprising returning some products produced by said first hepatocytes to the patient.
Claim 50
Dependent Claim
16 words
The method of claim 44, further comprising treating said products prior to return to said patient.
Claim 51
Dependent Claim
13 words
The method of claim 39, further comprising flushing nutrients through said perfusion compartment.
Claim 52
Independent Claim
157 words
A method of using a hepatocyte perfusion device comprising: providing a perfusion device including a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, biocompatible polymer support means in said hepatocyte compartment, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages, and causing perfusion liquid to flush through said inlet means, said perfusion compartment, and said outlet means.
Claim 53
Independent Claim
157 words
A method of using a hepatocyte perfusion device comprising: providing a perfusion device including a chamber having a perfusion inlet means and a perfusion outlet means, a porous membrane means mounted in and secured to said chamber so as to define a perfusion compartment and an adjacent, separate hepatocyte compartment in said chamber, biocompatible polymer support means in said hepatocyte compartment, said perfusion inlet means and said perfusion outlet means being in fluid communication with said perfusion compartment, said membrane means being made of a biocompatible polymer, at least one of a first oligosaccharide and a first lectin fixedly attached to a portion of at least one of said support means and said membrane means facing said hepatocyte compartment, and first hepatocytes attached to said at least one of a first oligosaccharide and a first lectin via oligosaccharide-lectin recognition linkages, and causing perfusion liquid to flush through said inlet means, said perfusion compartment, and said outlet means.
Claim 54
Dependent Claim
13 words
The method of claim 47, wherein said first hepatocytes have cytochrome P450 activity.
Claim 55
Dependent Claim
36 words
The method of claim 41, wherein said first lectin is a member selected from the group consisting of Ricinus communis agglutinin, wheat germ agglutinin, Pisum sativum agglutinin, Lens culinaris agglutinin, Phaseolus vulgaris agglutinin, and Concanavalin A.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-08-26 | 1995-02-25 | 1995-08-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-08-26 | 1999-02-25 | 1999-08-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-08-26 | 2003-02-25 | 2003-08-27 | $7700.00 | Window Closed / Lapsed |