US005916800A
`5,916,800
`(114) Patent Number:
`United States Patent 55
`Elizondoet al.
`[45] Date of Patent:
`Jun. 29, 1999
`
`
`[54] CARDIOVASCULAR BIOREACTOR
`APPARATUS AND METHOD
`
`[56]
`
`References Cited
`U.S. PATENT DOCUMENTS
`
`[75]
`
`Inventors: David R. Elizondo, St. Paul, Minn.;
`Todd D. Campbell, Hillsboro, Oreg.;
`Robert P. Totten, Placerville, Calif.
`
`[73] Assignee: St. June Medical, Inc., St. Paul, Minn.
`
`[21] Appl. No.: 08/796,573
`a.
`[22]
`Filed:
`Feb. 6, 1997
`Related U.S. Application Data
`
`2/1972 Goldhaber oo...eee 435/284.1
`3,639,084
`8/1973 Belzeretal. ..
`w. 435/284.1
`3,753,865
`11/1973 De Roissart..
`w 435/284.1
`3,772,153
`3,777,507 12/1973 Burtonetal. ..
`w. 435/284.1
`3,843,455
`10/1974 Bier ow.
`.. 435/284.1
`4,745,759
`5/1988 Baueret al.
`...
`.. 435/284.1
`5,285,657
`2/1994 Bacchietal. ..
`.. 435/284.1
`5,326,706
`7/1994 Yland et al.
`...
`w. 435/284.1
`5,338,662
`8/1994 Sadri wi...
`w. 435/284.1
`5,362,622 11/1994 O’Dell et al.
`..
`. 435/284.1
`Primary Examiner—David A. Redding
`Attorney, Agent, or Firm—Hallie A. Finucave; William T.
`Bundren
`[57]
`
`ABSTRACT
`
`[63] Continuation of application No. 08/482,990, Jun. 7, 1995,
`abandoned.
`Ls
`.
`[SD]
`Tint, (de oeccc cceessccsssssneeecceesnsnneeeee C12M 3/00
`The invention involves a method and apparatus for process-
`.
`:
`ing biological material, such as heart valves and vascular
`[52] U.S. CD. eeecseessesseeneenes 435/284.1; eeaoyt
`:
`fts.
`[58] Field of Search.
`...ccccccscsscsssseee 435/284.1, 2891, °°
`435/307.1
`
`12 Claims, 6 Drawing Sheets
`
`
`
`4%44 10
`
`
`
`
`
`
`
`
`8 HEAD ROLLER PUMP
`
`BHEAD ROLLER Pup
`
`NUTRIENT FEED LOOP
`
`0.2 MICRON
`FILTER
`
`PAGE 1 OF 14
`
`WATERS TECHNOLOGIES CORPORATION
`
`EXHIBIT 1011
`
`WATERS TECHNOLOGIES CORPORATION
`EXHIBIT 1011
`
`PAGE 1 OF 14
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`

`

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`U.S. Patent
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`Jun. 29, 1999
`
`Sheet 1 of 6
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`5,916,800
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`PAGE 2 OF 14
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`PAGE 2 OF 14
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`U.S. Patent
`
`Jun. 29, 1999
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`Sheet 2 of 6
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`5,916,800
`
` IS\SERY
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`PAGE 3 OF 14
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`PAGE 3 OF 14
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`

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`U.S. Patent
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`Jun. 29, 1999
`
`Sheet 3 of 6
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`PAGE 4 OF 14
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`PAGE 4 OF 14
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`U.S. Patent
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`Jun. 29, 1999
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`Sheet 4 of 6
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`5,916,800
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`FIG.4
`
`WATERBATHFLUIDWARMER
`
`
`(37°C)
`
`
`
`
`
`8HEADROLLERPUMP
`
`PAGE 5 OF 14
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`PAGE 5 OF 14
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`U.S. Patent
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`Jun. 29, 1999
`
`Sheet 5 of 6
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`5,916,800
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`PAGE6 OF 14
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`PAGE 6 OF 14
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`U.S. Patent
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`Jun. 29, 1999
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`Sheet 6 of 6
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`5,916,800
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`PAGE7 OF 14
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`5,916,800
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`1
`CARDIOVASCULAR BIOREACTOR
`APPARATUS AND METHOD
`
`This is a Continuation of application Ser. No. 08/482,
`990, filed Jun. 7, 1995 now abandoned.
`
`TECHNICAL FIELD
`
`The invention involves a method and apparatus for pro-
`cessing biological material.
`
`10
`
`BACKGROUND OF THE INVENTION
`
`2
`space, and has the capability of providing multiple tasks and
`multiple products.
`The system according to the invention includesa biologi-
`cal material processing chamber, an environmental control
`circuit, a nutrient supply circuit, and a pulse evaluation unit.
`The methods and devices according to the present inven-
`tion have the added advantage of relatively low costs in
`time, effort, personnel, and equipment required to process,
`evaluate, store, and ship biological material(s).
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`Surgical implantation of tissue is utilized to replace and/or
`repair human tissues. For example, hereditary defects,
`disease, and/or
`trauma may damage tissues such that
`replacement and/or repair is desirable. These implantable
`tissues may be provided by individual human donors.
`However, because of the scarcity of appropriate human
`donors, non-humantissues have been increasingly employed
`instead. Such biological tissues have been used to replace
`heart valves,
`ligaments,
`tendons and skin, among other
`tissues.
`
`Care must be taken in preparing, manufacturing, storing,
`and shipping these replacement materials. While many have
`focused on the design and construction of the replacement
`materials themselves, fewer have focused on the structures
`that would aide in constructing, evaluating, and storing
`biological material such as heart valves and vasculargrafts.
`For example, some devices or methods have tried to
`accomplish the culturing under subphysiologic conditions.
`There is a need for a system and apparatus for evaluating
`biological material under normal and supra-physiological
`conditions. Some of this need is represented by a need to
`modify the current pulse duplicator and accelerated life
`testers.
`
`SUMMARYOF THE INVENTION
`
`15
`
`20
`
`25
`
`FIG. 1 is an embodiment of a system according to the
`invention.
`
`FIG. 2 is an exemplary embodimentoffirst compartment
`40 according to the invention.
`FIG. 3 is an exemplary embodiment of second compart-
`ment 50 according to the invention.
`FIG. 4 is an exemplary embodiment of an environmental
`control circuit according to the invention.
`FIG. 5 is an exemplary embodiment of a nutrient feed
`circuit according to the invention.
`FIG. 6 is an alternative embodimentof a pulse evaluation
`unit according to the invention.
`
`SPECIFIC DESCRIPTION OF THE INVENTION
`
`30
`
`35
`
`45
`
`50
`
`55
`
`The system according to the invention includesa biologi-
`cal material processing chamber, an environmental control
`circuit, a nutrient supply circuit, and a pulse evaluation unit.
`The present invention also includes a biological material
`processing, evaluation, and storage system comprising a
`chamber for processing, evaluating, and storing a pre-
`determined biological material, such as one or more heart
`valves; a temperature circuit in fluid communication with
`the chamber; and a nutrient supply circuit in fluid commu-
`Furthermore, testing and monitoring methods and devices
`nication with the chamber. This system mayalso include a
`are typically not conducted in sterile and aseptic conditions.
`pulse evaluation circuit.
`Mountingthe fixture in a sealable chamberfor use in storage
`40
`Processing, as used herein, refers to all of the various
`and shipping has not been accomplished. There is a need to
`steps in constructing and preparing biological material for
`provide a system and apparatus that providesasterile
`implantation, from the initial construction protocols to stor-
`environment throughout the construction, testing, and stor-
`ing and shipping the prepared implant. Processing also
`age stages. This need extends to providing a test and
`includes testing and evaluating biological material, such as
`evaluation container that also may be used as a storage and
`heart valves, including testing and evaluating new designs.
`shipping container.
`The invention allows the sterile mounting, culturing,
`Furthermore, the design of some of the equipment for
`monitoring, and functional evaluation of biological material,
`working with biological material, such as the mandrels for
`such as heart valves and/or vascular grafts, within a single
`working with heart valves and vascular grafts, are some-
`chamber/system at various physiological conditions, 1e.,
`times awkward to use and do not adequately address the
`below, at, or above normal physiologic conditions.
`problemsof the entire manufacturing process. For example,
`The present invention also comprises an apparatus for
`a single valve mounting and release system has not been
`processing and storing biological material comprising a
`accomplished. There is a need to provide a new mounting
`chamber having a first compartment incorporating an envi-
`system for biological materials.
`ronmental control flow path and a nutrient feed flow path,
`and a second chamberfor evaluating the biological material,
`the second chamberincluding a mountsuitable for mounting
`and testing the biological material.
`The present invention also comprises a method for pro-
`cessing biological material comprising fixing a biological
`material to a suitable mount, exposing the biological mate-
`rial
`to predetermined evaluation conditions, ending the
`evaluation conditions, and storing the biological material in
`the chamber. The method according to the invention may
`also include exposing the biological material to a nutrient
`feed, and mayfurther include controlling the environmental
`conditions within the system. The method may include
`sealing the biological material in its processing chamber,
`
`The present invention provides a method, apparatus, and
`system to process and ship biological products, typically
`cardiovascular products, within a single sterile, aseptic sys-
`tem and apparatus.
`The present invention also provides an integral system
`and apparatus to process biological materials, such as heart
`valves and vascular grafts.
`The present invention also provides a processing chamber
`that may also be used as a storage and/or shipping container.
`This single system provides culturing, monitoring,
`testing, and storage capabilities in a minimum amountof
`
`60
`
`65
`
`PAGE 8 OF 14
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`5,916,800
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`3
`and may further include shipping the sealed biological
`material in the same processing chamber.
`As used herein, biological material refers to any cellular
`matter for which it may be desirable to form into a prede-
`termined shape, to evaluate, and to store. Typically “bio-
`logical tissue”refers to a collagen-containing material which
`may be derived from different animal species,
`typically
`mammalian. Suitable sources include, but are not limited to,
`bovine, porcine, equine, ovine, kangaroo, rabbit, boar, bear,
`and human.
`
`The biological material is typically a soft tissue suitable
`for implantation, such as bioprosthetic tissue or the like, but
`the invention should not be limited thereby. Specific
`examples include, but are not
`limited to, heart valves,
`particularly porcine heart valves; aortic roots, walls, and/or
`leaflets; pericardium, preferably bovine pericardium or the
`like, and products derived from pericardium, such as a
`pericardial patch; epithelial of fibrous connective tissue
`derived materials such as dura mater, fascia lata, amnion,
`cartilage, and the like; homograft tissues, such as aortic
`homografts and saphenous bypass grafts;
`tendons;
`liga-
`ments; skin patches; blood vessels, particularly bovine arter-
`ies and veins, and human umbilical tissue, such as veins;
`bone; and the like. The biological material may also include
`segments, portions, or parts of any of the materials noted
`above. Any other biologically-derived materials which are
`known, or become known,as being suitable for processing
`in accordance with the invention are within the contempla-
`tion of the invention.
`
`For the purpose of some embodiments of the invention,
`the term biological material will also encompass synthetic
`and/or mechanical material which are sometimes used to
`reinforce, substitute, or replace collagen-containing materi-
`als. For example, heart valves may be wholly natural porcine
`heart valves, but they may also include polymeric or syn-
`thetic structures, or they may wholly comprise synthetic
`materials, such as metal, polymers, thermoplastics, fabric,
`and the like. The use and structure of these synthetic/
`mechanical structures are well known, and are included
`within the invention.
`
`Exemplary processing systems according to the invention
`are shown in FIGS. 1-3. For example, system 10 may
`include a processing chamber 11, environmental control
`circuit or flow path 20, nutrient supply circuit or flow path
`30, and, optionally, pulse evaluation umit or flow path 60. In
`a preferred embodiment of the system,
`the system is an
`integral or unitary system, even more preferably, with at
`least one removable chamber 12/13 also suitable for storing
`and/or shipping the biological material (see FIG. 3).
`The processing chamber 11 is a container, housing or the
`like for processing and storing the biological material. The
`chamber maybeof different configurations, as dictated and
`found desirable for a particular biological material. In some
`embodiments of the invention, the same chamber may be
`used to construct,
`test and evaluate, store, and ship the
`biological material. In the preferred embodiments of the
`invention, chamber 11 is used to process the biological
`material, except for storing and/or shipping.
`Releasable chambers 12 and 13 is a container, housing or
`the like for processing the biological material. The chamber
`may be of different configurations, as dictated and found
`desirable for a particular biological material. Chambers 12
`and 13 typically include a mount 14 or the like for posi-
`tioning the biological material in the proper position for
`testing, evaluating, constructing, storing, and/or shipping. In
`a preferred embodiment of the invention, chambers 12 and
`
`4
`13 may be sealed and/or released from the system,e.g., by
`heat sealing the inlet and the outlet of the releasable
`chamber, or by sealing a portion of the conduit upstream and
`downstream of the chamber.
`
`it will be
`As will be explained in more detail below,
`appreciated that should it be desirable to process only one
`biological material in a processing circuit, one of releasable
`chambers 12 and 13 may be a check valveorthe like. In this
`embodiment of the invention, chamber 12 or 13 would not
`need to be releasable or sealable.
`
`The environmental control circuit 20, shown in FIGS. 1
`and 4,
`is in fluid communication with chamber 11, and
`provides temperature control to the system 10 or parts of the
`system. This circuit 20 may be variously configured, and
`typically includes a pump 22, a first heat exchanger 21 to
`regulate the temperature of the fluid passing through it, and
`a second heat exchanger 23, preferably in the chamber11,to
`regulate the temperature of the chamber 11, any fluids or
`nutrient solutions, and the biological material. Also,
`the
`environmental control circuit 20 may be used to alter the
`temperature of the system 10, or parts of the system, when
`evaluating the biological material under pre-determined
`stress or accelerated life conditions.
`
`Alternatively, the environmental control circuit 20 may
`include one or more flow paths or individual circuits. The
`exemplary embodiment illustrated in FIG. 4 showseight
`circuits, but any number of circuits may be used.
`It
`is
`intendedthat the invention is not to be limited by the number
`of environmental control circuits.
`
`The nutrient supply circuit 30, shown in FIGS. 1 and 5, is
`in fluid communication with the chamber 11, and provides
`nutrients and the like to maintain, sustain, and optionally,
`promote the growth of the biological material. The content
`and configuration of the nutrient supply circuit may be
`variously configured for a specific biological material and
`for a particular need, as is explained in more detail below.
`Alternatively, the nutrient supply circuit 30 may include
`one or moreflow paths or individual circuits. The exemplary
`embodimentillustrated in FIG. 5 shows eight circuits, but
`any numberof circuits may be used. It is intended that the
`invention is not to be limited by the number of nutrient
`supply circuits.
`The pulse evaluation circuit 60 is used to process the
`biological material
`in a pre-determined manner. For
`example, circuit 60 may be used to evaluate the function,
`durability, and design of a biological material, such as a
`heart valve. In one embodiment of the invention, the pulse
`evaluation circuit 60 tests one or more heart valves under
`conditions similar to the conditions the valve will be sub-
`jected to after implantation. The pulse evaluation unit may
`also be used to test and evaluate new heart valve designs.
`In accordance with the invention, the pulse evaluation
`circuit 60 may include various components and may be
`variously configured. For example,
`the pulse evaluation
`circuit shown in FIG. 1 is in fluid communication with
`
`second compartment 50 of chamber 11. This exemplary
`circuit includes a motor 61, pump, or the like for alternat-
`ingly producing pressure and a vacuum; a conduit 62 for
`establishing fluid communication with chamber 11; and a
`diaphragm 63 orthe like interposed in the circuit 60 between
`the motor 61 and an inlet of chamber 11. In the illustrated
`embodiment, the diaphragm formsa portion of the inlet into
`chamber 11.
`
`An alternative configuration of pulse evaluation circuit 60
`is illustrated in FIG. 3. In this exemplary embodimentof the
`invention, the circuit 60 includes a pneumatic pump 64 or
`
`10
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`15
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`20
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`25
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`5,916,800
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`5
`the like, in fluid communication with chamber 11 through
`conduit 62. The flow path into and out of chamber 11 may
`be through inlet 41 and inlet 42 (part of the nutrient supply
`circuit), or may through its separate inlet and outlet (not
`shown). One or more chambers 12 and 13 maybeinterposed
`in conduit 62 between the pump 64 and the chamber 11. As
`illustrated in FIGS. 4 and 5, the pulse evaluation circuit may
`comprise in part the nutrient supply circuit (FIG. 5) and/or
`the environmental control circuit (FIG. 4). In an exemplary
`embodimentpartially illustrated in FIG. 4 and 5, the pulse
`evaluation circuit may include more than one flow path or
`circuits. FIGS. 4 and 5 showseight circuits, but any number
`of circuits may be used. It is intended that the invention is
`not to be limited by the numberof pulse evaluation circuits.
`As noted in more detail below, the individual parts which
`constitute a biological material processing assembly 10 may
`vary according to its intended use. For example, it may be
`desirable to test and evaluate the competencyof a biological
`material, such as a heart valve. It may also be desirable to
`seed a biological material, such as a vascular graft or a heart
`valve. It may be further desirable to provide nutrient and
`environmental control systems. These and other uses will be
`explained in more detail below.
`filters,
`Any number and combinations of assemblies,
`containers, pumps, and conduits are suitable. One skilled in
`the art will recognize that the invention as described may be
`reconfigured into different combinations.
`the conduits,
`In accordance with the invention,
`assemblies, filters, and containers which constitute a bio-
`logical fluid processing assembly may be arrangedto define
`different flow paths. Since independent flow paths may be
`present, included within the scope of the present invention
`is the concurrent or sequential passage of separate fluids
`through the biological material processing assembly.
`Individual components of a processing system according
`to the invention will now be described.
`
`10
`
`20
`
`25
`
`30
`
`35
`
`The Chamber
`
`6
`In the illustrated
`include a pulse evaluation circuit 60.
`configuration, pulse evaluation unit 60 is in fluid commu-
`nication with chamber 11 through inlet 41 and outlet 42.
`The housing or chamber 11 may have a variety of con-
`figurations. Exemplary configurations are shown in the
`Figures.
`As noted above, in accordance with the invention, the
`biological material may then be placed or packaged in a
`container 12. In a preferred embodimentof the invention,
`the processed biological material is surrounded by nutrient
`solution when it is sealed and shipped. If seeding or the
`presence of cells in the nutrient fluid is not desirable, the
`biological material may be sealed and shipped in physiologi-
`cal salineor the like. Packaging preferably meansplacing in
`a container suitable for storage and/or shipping.
`The container 12/13 or chamber 11 may be constructed of
`any material compatible with a nutrient solution and capable
`of withstandingsterilization, e.g., by electron beam, gamma
`radiation, autoclave, acetylene oxide, or
`the like.
`In a
`preferred embodiment, the chamber11 or container 12/13 is
`formed of glass or polymeric plastic. Suitable plastic mate-
`rials include polyethylene; acrylates such as polymethyl
`methacrylate and polymethyl acrylate; polymethyl pentene-
`1; polyvinyl chloride; vinyl chloride-vinylidene chloride
`copolymers; polypropylene; urea-formaldehyde copolymer;
`melamine-formaldehyde copolymer; polystyrene; polya-
`mide; polytetrafluoroethylene; polyfluorotrichloroethylene;
`polycarbonates; polyesters; phenol-formaldehyde resins;
`polyvinyl butyryl, cellulose acetate; cellulose acetate propi-
`onate; ethyl cellulose; polyoxymethylene; and polyacryloni-
`trile. In a preferred embodiment, the container is constructed
`of polypropylene, polyethylene, and/or epoxies.
`It
`is
`intended that the invention should not be limited by the type
`of container and seal being employed; other materials may
`be used, as well as mixtures, blends, and/or copolymers of
`any of the above.
`Any housing, container, or chamber in a system of the
`invention also preferably includes a transparent portion
`positioned to permit observation within the chamber. For
`example, the transparent portion may be a window in a cover
`or wall. Alternatively, the entire housing may be formed
`from a transparent material, such as a transparent plastic.
`
`Environmental Control
`
`40
`
`45
`
`50
`
`A processing and evaluation chamber according to the
`invention may be variously configured. The chamber will
`typically include a housing having at least one compartment,
`and the housing will typically have at least one inlet and at
`least one outlet. In some preferred embodiments of the
`invention, the chamber will include a mountfor positioning
`and retaining a biological material.
`Although the environmental control circuit may be vari-
`For example, FIG. 1 shows a two-compartment chamber
`ously configured, the illustrated environmental control cir-
`11. FIG. 3 shows a one-compartment chamber 11. In the
`cuit 20 comprises a heat exchanger 21 and a pump 22in fluid
`various configurations of the chamber,
`there may be
`communication with the chamber 11. In some embodiments
`included one or more nutrient flow paths, one or more
`of the invention, the environmental control circuit 20 may
`environment control flow path, and one or more pulse
`include an arrangement of separate structures and flow
`evaluation flowpaths.
`paths, each providing separate fluid communication with the
`For example, in the configuration illustrated in FIG. 1,
`chamber and/or an individual biological material.
`chamber 11 includes a first compartment 40 havingafirst
`inlet 41 andafirst outlet 42 for providing a nutrient flow path
`Nutrient Supply
`through the chamber. The chamber 11 may also include a
`second inlet 43 and a second outlet 44 for providing an
`environmental control flow path through the chamber11. In
`a preferred embodimentfirst compartment 40 includes a heat
`exchange tube 23. The heat exchange tube 23 may be
`variously configured, and in the preferred embodiment, the
`tube 23 has a serpentine configuration within the chamber.
`In another example,
`in the configuration illustrated in
`FIG. 3, system 10 includes a chamber 11 having one
`compartment in fluid communication with at least one of a
`nutrient supply circuit and an environmental control circuit.
`In this embodiment of the invention, chamber 11 may also
`
`60
`
`Although the nutrient supply circuit may be variously
`configured, the illustrated nutrient supply circuit 30 com-
`prises a filter 31 and a pump 32 in fluid communication with
`the chamber 11. The nutrient supply circuit 30 may also
`include a source of nutrient solution, a fill port, and a drain
`(not shown).
`In accordance with the invention, the nutrient solution
`may be a variety of solutions, as pre-determined for a
`particular purpose. For example, the nutrient solution may
`be physiological saline, typically used to maintain, store,
`and/or ship the biological material. In other embodiments of
`
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`5,916,800
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`7
`the invention, the nutrient solution, such as the well known
`and commercially available OMEM solution, contains
`nutrients, vitamins, minerals, antibiotics, and the like. In
`accordance with some embodiments of the invention, this
`solution, or a nutrient solution like it, will also include cells
`suitable for seeding a biological material, such as a heart
`valve or a vascular graft. It is intended that the invention is
`not to be limited by the type or content of nutrient solution
`passing through the circuit 30.
`As used herein, physiologically acceptable fluid refers to
`any fluid or additive suitable for contacting biological mate-
`rial. The physiologically acceptable fluid may also include
`nutrients and the like. Exemplary physiologically acceptable
`fluids include but are not limited to preservative solutions,
`aldehyde solutions,saline solution, an isotonic (about 0.9%)
`saline solution, or about a 5% albumin solution or suspen-
`sion. It is intended that the present invention is not to be
`limited by the type of physiologically acceptable fluid used.
`
`Pulse Drive Unit
`
`In some embodimentsof the invention, the system 10 may
`include one or more biological material evaluation units or
`circuits. For example, in the illustrated embodiment, bio-
`logical material such as heart valves may be evaluated using
`a pulse evaluation circuit 60. The pulse evaluation circuit
`may be variously configured. An important feature of the
`pulse evaluation circuit 60 is a pneumatic portion 61 for
`testing the competency of one or more heart valves. The
`pneumatic portion may include structures for regulating
`pressure and structures for establishing a vacuum. The unit
`60 mayalso include a timing circuit, preferably a solid state
`timing circuit, and may includefixed and/or variable timing
`controls.
`
`the pulse
`In a preferred embodiment of the invention,
`evaluation circuit 60 provides timed pulsatile compressed air
`and vacuum to a suitable diaphragm pump via a three way
`diverter valve (not shown) actuated by the timing circuit.
`
`Pressure Differential Generator
`
`A system according to the invention may comprise a
`pressure differential generator e.g., a pumporthe like, which
`is suitable for inducing fluid flow from chamber11 to other
`parts of the system, or inducing flow from otherparts of the
`system to chamber 11. The pressure differential generator is
`operatively associated with a biological material processing
`assembly, an example of which is shown as 22 and 31 in
`FIG. 1. The pressure differential generator may also be
`operatively associated with one or more fluid flow paths
`within the system 10, or with one or more structures within
`a circuit.
`
`Movement of fluid through the system is effected by
`maintaining a pressure differential between the chamber and
`the destination of the fluid (e.g., a filter or a temperature
`control unit). Exemplary meansof establishing this pressure
`differential may be by a mechanical memberbearingdirectly
`against a fluid-collection container, mechanical expressor,
`gravity head, applying pressure to the collection bag by hand
`or with a pressure cuff, or by an in-line pump.
`
`Filters
`
`The filter 31 is chosen so that the sterility of the system
`is not compromised. The filter 31 is particularly suited for
`use in closed systems. Embodiments of the present invention
`may be used preferably with a sterile fluid, such as a
`biological fluid. A sterile fluid is one which is substantially
`
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`PAGE 11 OF 14
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`8
`free of viable contaminating microorganisms. Systems
`according to the invention maydefine a fluid communication
`path wherein the fluid is maintained free of viable contami-
`nating microorganisms, or the sterility of the fluid is not
`adversely affected by the passage of the fluid through the
`assembly.
`A variety of filters may be used, provided the requisite
`properties of the particular porous medium are achieved.
`These include the necessary strength to handle the differen-
`tial pressures encountered in use and the ability to provide
`the desired permeability without the application of excessive
`pressure. In a sterile system, the porous medium should also
`preferably have a pore rating of about 0.2 micrometeror less
`to preclude bacteria passage.
`Freedom from contaminants refers to a relative amount of
`
`contaminants andis variously defined accordingto a specific
`industry, fluid and/or intended use. For example, a biological
`fluid which is substantially free of contaminants is consid-
`ered free of viable microorganisms, andis typically referred
`to as “sterile”.
`
`Automated Control Arrangement
`
`In accordance with the invention, an automated control
`arrangement, in response to predetermined conditions, may
`send and receive signals, and control the overall sequence
`and flow of fluid or gas from one portion of the system to
`another. The control arrangement may be connected to the
`various elements of the system, and may include one or
`more connections to a container, to a conduit, to a specific
`element in the biological material processing assembly or
`the pressure differential generator, to a valve, or the like.
`For example,
`the automated control arrangement may
`include one or more devices, switches, and/or indicators or
`monitors to achieve a desired purpose, including, but not
`limited to: a power switch; a start switch; a stop switch; a
`sequence selection switch; weight sensor devices, switches,
`and/or indicators;
`time sensor devices, switches, and/or
`indicators; optical sensor devices, switches, and/or indica-
`tors; and fluid flow sensor devices, switches, and/or indica-
`tors.
`
`It is intended that each of these sensors monitor a prede-
`termined condition, and react or provide feedback according
`to a predetermined or pre-set array of variables.
`Preferably, the pressure regulating mechanism, such as
`that shown as 64 in FIG. 3, may include a four way
`pneumatic valve capable of connecting a flexible hoseto the
`input or to the output of a standard piston pump. The
`pneumatic valve may beelectronically controlled by the
`control unit. Additionally, there may be a plurality ofrelief
`valves and a pressure sensor electronically controlled and
`monitored by the control unit. In this manner, the control
`unit may control and monitor the pressure or vacuum
`exerted on the pulse evaluation circuit.
`As noted above, the invention may include a variety of
`other configurations and assemblies. Some of these varia-
`tions will now be described.
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`As with all illustrated embodiments herein, a number of
`variations in the illustrated constructions are envisioned.
`
`60
`
`Each of the assemblies or containers may be in fluid
`communication through conduits, typically flexible tubing,
`and preferably plasticized PVC. A seal, valve, clamp, pinch
`clamp, or transfer leg closure or cannula may also be
`positioned in or on the tubing or in or on the chamber. In
`accordance with the present
`invention,
`the assemblies,
`containers, and conduits may be previously connected in a
`
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`5,916,800
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`9
`closed, sterile manner, or segments of the system may be
`inserted into a closed system in a sterile manner.
`As used herein, adapted for communication refers to any
`means or methods for establishing fluid flow through the
`system. For example,
`two conduits may be heat sealed
`together, to form a sterile connection using known connec-
`tion devices; or a conduit may have a connector adapted to
`receive or connect to a mated connector on another conduit;
`or the connector may be a spike, adapted to be inserted in a
`fluid container, such as a nutrient-containing bagorthe like.
`As used herein, connector refers to any structure used to
`form a joint or to join itself to another piece. These con-
`nectors establish a flow path through various elements of an
`assembly or system. Connector, as used herein, typically
`refers to penetrating connectors, such as a spike, cannula, or
`needle; and mating connectors, such as Luer-type, screw-
`type, friction-type, or connectors which are bonded together.
`It is intended that the present invention is not to be limited
`by the type of connector or connection used for establishing
`fluid flow through the conduit.
`A flow control device, such as a seal, valve, clamp, pinch
`clamp, roller, transfer leg closure, or the like is typically
`located in or on the tubing and/or containers. In accordance
`with the invention, a flow control device may be positioned
`on or in any or all of the conduits in order to facilitate a
`desired function, 1.e., establishing a desired flow path for a
`fluid or gas. It is intended that the present invention should
`not be limited by the number, placement, or use of such flow
`control devices.
`
`Other variations are also envisioned. For example, where
`the connector and fluid conduit comprise separate
`components, they could be connected by a variety of other
`means, e.g. mating threadedfittings. Alternatively, a bracket
`may be attached to a sleeve, either formed integrally with the
`bracket or otherwise connected thereto. This sleeve may be
`connected to a section of tubing through telescopic
`engagement, i.e. a coaxial friction fit wherein one member
`is inserted within the other, with friction between the two
`membersretaining the coupling. In a