(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`(19) World Intellectual Property
`Organization
`International Bureau
`
`(43) International Publication Date
`18 May 2017 (18.05.2017)
`
`WIPOI PCT
`
`\9
`
`(10) International Publication Number
`
`WO 2017/083252 A1
`
`(51)
`
`International Patent Classification:
`A613 5/15 (2006.01)
`G01N 33/48 (2006.01)
`B01D 61/38 (2006.01)
`
`(21)
`
`International Application Number:
`
`PCT/US2016/060903
`
`(22)
`
`International Filing Date:
`
`Inventors; and
`(72)
`(71) Applicants : KUSHON, Stuart, A. [US/US]; 25262 Ar-
`der Court, Lake Forest, CA 92630 (US). ZAMBA, Gene
`[US/US]; 25859 Anzio Way, Valencia, CA 91355 (US).
`RUDGE, James, Byron [GB/GB]; 100 The Chesils, Cov—
`entry CV3 SBL (GB). JARING, Carolyn [PH/US]; 21 105
`Shearer Avenue, Carson, CA 90745 (US).
`
`8 November 2016 (08.11.2016)
`English
`
`(74)
`
`Agent: GANJIAN, Peter; Patent Law Agency, LLC, 2029
`Verdugo Blvd, #1031, Montrose, CA 91020 (US).
`
`Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY,
`BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM,
`DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,
`HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR,
`KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME,
`
`[Continued on next page]
`
`(25)
`
`(26)
`
`(30)
`
`(71)
`
`Filing Language:
`
`Publication Language:
`
`English (81)
`
`Priority Data:
`62/253,577
`10 November 2015 (10.11.2015)
`15/345,079
`7 November 2016 (07.11.2016)
`
`US
`US
`
`Applicant: NEOTERYX, LLC [US/US]; 421 Amapola
`Ave., Torrance, CA 90501 (US).
`
`(54)
`
`Title: PLASMA EXTRACTION DEVICE
`
`(57) Abstract: The present invention discloses a plasma extraction device
`for generating fixed, predetermined quantity of plasma and for dry-transport
`of obtained plasma for automated assay. Plasma extraction device includes a
`plasma extractor assembly comprising an absorbent probe that wicks a pre-
`determined volume of a liquid sample from a liquid source, a separator that
`generates plasma From the wicked liquid sample, and an absorbent reservoir
`that stores fixed, predetermined quantity of the generated plasma for dry—
`transport and automated assay thereof.
`
`.04
`
`
`
`FIG. 1A
`
`
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`WO 2017/083252 A1 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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`(84)
`
`MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO,
`NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU,
`RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH,
`_
`TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN,
`Publlshed:
`ZA, ZM, ZW.
`lAt.213
`h
`l
`l.
`—
`.th't
`WI m erna zona searc repor ( r
`())
`Designated States (unless otherwise indicated, for every
`kind afregional protection available): ARIPO (BW, GH, — before the expiration of the time limit for amending the
`GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ,
`claims and to be republished in the event of receipt of
`TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU,
`amendments (Rule 48.2(h))
`TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE,
`DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT,
`
`LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE,
`SI, SK, SM, TR), OAPI (BF, BJ, CP, CG, C1, CM, GA,
`GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG).
`
`

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`WO 2017/083252
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`PCT/USZOl6/060903
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`[001] PLASMA EXTRACTION DEVICE
`
`[002] CROSS—REFERENCE TO RELATED APPLICATIONS
`
`[003] This Application claims the benefit of priority of co—pending U.S. Utility
`
`Provisional Patent Application 62/253,577, filed 10 NOV 2015, the entire disclosure
`
`of which is expressly incorporated by reference in its entirety herein.
`
`[004] All documents mentioned in this specification are herein incorporated by
`
`reference to the same extent as if each individual document was specifically and
`
`individually indicated to be incorporated by reference.
`
`[005]
`
`It should be noted that throughout the disclosure, where a definition or use Of a
`
`term in any incorporated document(s) is inconsistent or contrary to the definition of
`
`that term provided herein, the definition of that term provided herein applies and the
`
`definition of that term in the incorporated document(s) does not apply.
`
`[006] BACKGROUND OF THE INVENTION
`
`[007] Field of the Invention
`
`[008] One or more embodiments of the present invention relate to a sample
`
`collection device.
`
`[009] Description of Related Art
`
`[0010] Conventional methods of extraction or separation of plasma are well known
`
`and have been in use for a number of years, which include centrifugation, pressure
`
`induced plasma separation devices, volume induced plasma separation device, etc.
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`[0011] Centrifugation is a very well known method used for separating plasma, which
`
`requires the use of complex devices and further, complex methods and systems for
`
`sample tracking (allocating, labeling, etc.) the extracted liquid plasma for safe
`
`transport and continuous association with a test subject. Once separated by
`
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`
`centrifugation, the actual extraction of liquid plasma itself is a non—automated process,
`
`requiring the use of skilled lab technicians that may inadvertently introduce operator
`
`errors in the extraction process of the liquid plasma and also add to the overall cost.
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`Centrifugation has a major disadvantage in that it cannot be easily used to generate
`
`plasma at the point of care.
`
`[0012] Pressure (positive or negative - vacuum) induced plasma generation may use
`
`conventional pumps (very large and complex) to force liquid (e.g., blood) through a
`
`well-known plasma separator to generate liquid plasma. A non-limiting example of a
`
`plasma separator is VIVID PLASMA SEPARATOR MEMBRANETM manufactured
`
`by PALL CORPORATION. Drawbacks with currently available pressure induced
`
`plasma generation systems are similar to centrifugation systems with respect to the
`
`use of additional equipment, need for complex sample tracking, use of skilled lab
`
`technicians, and accounting for operator errors.
`
`It should be noted that convention
`
`pressure induced plasma generation (positive or negative - vacuum) move wet
`
`"plasma" fluid into a tube for later analysis, which is an additional drawback and may
`
`be considered as bio-hazard in certain jurisdictions.
`
`[0013] A volume induced plasma generation may also use the well—known plasma
`
`separator with a conventional lateral flow device. In volume induced plasma
`
`generation schemes, fairly large volume of liquid (for example, large volume of water
`
`mixed with desired amount of blood) is poured onto a container that holds the plasma
`
`separator, with blood plasma generated due to sheer volume of liquid continuously
`
`passing through the plasma separator. The lateral flow device may then absorb the
`
`generated plasma by capillary action. It should be noted that an additional drawback
`
`with volume induced plasma generation is dilution of plasma and hence, loss in
`
`quantitative knowledge of plasma concentration resulting in qualitative rather than
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`quantitative assay.
`
`[0014] Accordingly, in light of the current state of the art and the drawbacks to
`
`current plasma extraction methods mentioned above, a need exists for plasma
`
`extraction system and method that would use capillary action (or gravity) as a motive
`
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`
`force to extract accurate quantity (amount) of plasma and hence, known concentration
`
`of plasma from a source of liquid without the use of external devices such as
`
`centrifuges, pumps, additional volume of liquid, etc. Further, a need exists for plasma
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`extraction system and method that would enable dry transport of fixed, predetermined
`
`quantity of plasma, even if the generated plasma is pressure (positive or negative -
`
`vacuum) induced.
`
`[0015] BRIEF SUlVllVIARY OF THE INVENTION
`
`[0016] A non—limiting, exemplary aspect of an embodiment of the present invention
`
`provides a device for extraction of plasma from a liquid sample, comprising:
`
`a first absorbent member that wicks liquid sample;
`
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`a second absorbent member that retains fixed, predetermined quantity of
`
`plasma; and
`
`a separator placed in physical contact between the first absorbent member and
`
`the second absorbent member for generating plasma from liquid sample;
`
`wherein: the plasma loaded second absorbent member is dry-transferred for
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`assay.
`
`[0017] Another non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a method for extraction of plasma, comprising:
`
`wicking a volume of a liquid sample from a liquid source through a first
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`capillary action;
`
`wicking the liquid sample to a separator through a second capillary action,
`
`with the separator generating a volume of a plasma,
`
`wicking a fixed, predetermined quantity of the plasma from the separator
`
`through a third capillary action,
`
`storing and dry-transferring of the collected plasma for assay.
`
`The second capillary action is mostly driven by differential porosity
`
`construction, and
`
`the third capillary action is mostly driven by differential in hydrophilic
`
`properties.
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`[0018] Yet another non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device, comprising:
`
`a handler assembly; and
`
`a plasma extractor module,
`
`wherein: the plasma extractor module is detachably associated with the
`
`handler assembly.
`
`[0019] A further non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device, comprising:
`
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`a handler assembly comprised of:
`
`a handler that houses an absorbent reservoir of a plasma extractor assembly;
`
`and
`
`a plasma extractor module that is detachably friction-fit secured to the handler
`
`assembly and includes a separator and an absorbent probe of the plasma extractor
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`assembly.
`
`[0020] Yet a further non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`a housing having a first piece and a second piece;
`
`the first piece includes one or more openings to frictionally secure one or more
`
`absorbent probes, with the second piece having at least one opening to frictionally
`
`secure at least one absorbent reservoir,
`
`the first piece and the second piece forming a compartment when assembled
`
`within which a separator is housed in physical contact in between the absorbent probe
`
`and the absorbent reservoir.
`
`[0021] Another non—limiting, exemplary aspect of an embodiment of the present
`
`invention provides a container, comprising:
`
`a tube configured assembly with air evacuated from within to create negative
`
`air pressure inside the tube assembly,
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`the tube assembly includes:
`
`a first detachable closure to air-tight close a first open end of the tube
`
`assembly; and
`
`a second detachable closure to air-tight close a second open end of the tube
`
`assembly.
`
`[0022] Yet another non—limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`a tube assembly with a detachable first closure and a detachable second
`
`closure with air evacuated from within to generate absolute lower air pressure inside
`
`the tube;
`
`the air evacuated tube includes:
`
`a first opening that is airtight closed by the first detachable closure;
`
`a second opening that is airtight closed by the detachable second closure; and
`
`a plasma extraction device that is housed inside the air—evacuated tube
`
`assembly, and removable through one of first and second opening.
`
`[0023] A further non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`a hermetically sealed air-evacuated tube assembly to draw liquid sample
`
`inside the tube assembly driven by pressure differential between inside and outside
`
`the tube assembly;
`
`a first absorbent member that wicks fixed, predetermined quantity of liquid
`
`sample;
`
`a second absorbent member that retains plasma; and
`
`a separator placed in physical contact between the first absorbent member and
`
`the second absorbent member for generating plasma from liquid sample;
`
`wherein: the plasma loaded second absorbent member is removed from tube
`
`assembly and dry-transferred for assay.
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`[0024] Yet a further non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`a tube assembly for drawing liquid sample inside the tube assembly driven by
`
`pressure differential between inside and outside the tube assembly generated by a
`
`pressure differential generator;
`
`a plasma extraction device positioned inside the tube assembly, comprising:
`
`a first absorbent member that wicks fixed, predetermined quantity of liquid
`
`sample drawn into the tube assembly;
`
`a second absorbent member that retains fixed, predetermined quantity of
`
`plasma, and
`
`a separator placed in physical contact between the first absorbent member and
`
`the second absorbent member for generating plasma from liquid sample,
`
`wherein: the plasma loaded second absorbent member is removed from tube
`
`assembly and dry—transferred for assay.
`
`[0025] Another non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`pressure differential generator for moving liquid sample from a source via an
`
`invasive probe and into a collection chamber of an intermediate adapter connected to
`
`the pressure differential generator, and
`
`a plasma extractor module positioned within the intermediate adapter, with an
`
`absorbent probe of the plasma extractor module extended to within the collection
`
`chamber, near egress opening of the invasive probe for receiving liquid sample.
`
`[0026] Yet another non-limiting, exemplary aspect of an embodiment of the present
`
`invention provides a device for extraction of plasma from a liquid sample,
`
`comprising:
`
`a plasma extraction device positioned within a tube assembly,
`
`the tube assembly is comprised of:
`
`a top closure; and
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`a lateral pressure differential generation outlet adapted to be detachably
`
`associated with a pressure differential generator.
`
`[0027] These and other features and aspects of the invention will be apparent to those
`
`skilled in the art from the following detailed description of preferred non—limiting
`
`exemplary embodiments, taken together with the drawings and the claims that follow.
`
`[0028] BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0029] It is to be understood that the drawings are to be used for the purposes of
`
`exemplary illustration only and not as a definition of the limits of the invention.
`
`Throughout the disclosure, the word “exemplary” may be used to mean “serving as an
`
`example, instance, or illustration,” but the absence of the term “exemplary” does not
`
`denote a limiting embodiment. Any embodiment described as “exemplary” is not
`
`necessarily to be construed as preferred or advantageous over other embodiments. In
`
`the drawings, like reference character(s) present corresponding part(s) throughout.
`
`[0030] FIGS. 1A to 1N are non-limiting, exemplary illustrations of various views of a
`
`plasma extraction device for extraction of plasma from a liquid sample in accordance
`
`with one or more embodiments of the present invention;
`
`[0031] FIGS. 2A to 2R are non—limiting, exemplary illustration of various views of a
`
`plasma extraction device for extraction of plasma from a liquid sample in accordance
`
`with one or more embodiments of the present invention;
`
`[0032] FIGS. 3A to 3F are non-limiting, exemplary illustration of various views of a
`
`plasma extraction device for extraction of plasma for a liquid sample in accordance
`
`with one or more embodiments of the present invention;
`
`[0033] FIGS. 4A to 4C are non—limiting, exemplary illustration of various views of a
`
`plasma extraction device for extraction of plasma from a liquid sample in accordance
`
`with one or more embodiments of the present invention;
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`[0034] FIGS. 5A to 5H are non-limiting, exemplary illustration of various views of a
`
`plasma extraction assembly for extraction of plasma from a liquid sample in
`
`accordance with one or more embodiments of the present invention;
`
`[0035] FIGS. 6A to 6F are non-limiting, exemplary illustration of various views of a
`
`plasma extraction assembly for extraction of plasma from a liquid sample in
`
`accordance with one or more embodiments of the present invention;
`
`[0036] FIGS. 7A to 7P are non-limiting, exemplary illustration of various views of a
`
`plasma extraction assembly for extraction of plasma from a liquid sample in
`
`accordance with one or more embodiments of the present invention; and
`
`[0037] FIGS. 8A-1 to 8D are non-limiting, exemplary illustration of various views of
`
`a plasma extraction assembly for extraction of plasma from a liquid sample in
`
`accordance with one or more embodiments of the present invention.
`
`[0038] DETAILED DESCRIPTION OF THE INVENTION
`
`[0039] The detailed description set forth below in connection with the appended
`
`drawings is intended as a description of presently preferred embodiments of the
`
`invention and is not intended to represent the only forms in which the present
`
`invention may be constructed and or utilized.
`
`[0040] It is to be appreciated that certain features of the invention, which are, for
`
`clarity, described in the context of separate embodiments, may also be provided in
`
`combination in a single embodiment. Conversely, various features of the invention
`
`that are, for brevity, described in the context of a single embodiment may also be
`
`provided separately or in any suitable sub-combination or as suitable in any other
`
`described embodiment of the invention. Stated otherwise, although the invention is
`
`described below in terms of various exemplary embodiments and implementations, it
`
`should be understood that the various features and aspects described in one or more of
`
`the individual embodiments are not limited in their applicability to the particular
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`embodiment with which they are described, but instead can be applied, alone or in
`
`various combinations, to one or more of the other embodiments of the invention.
`
`[0041] Throughout the disclosure, the term "separator" refers to filter membranes,
`
`non-limiting, non-exhaustive listing of examples of which may include nylon filters,
`
`cellulous filters, polyethylene filters, etc. Very specific, non-limiting examples of
`
`filter membranes (i.e., separators) that may be used in accordance with one or more
`
`embodiments of the present invention for example, are various types of VIVID
`
`PLASMA SEPARATOR IVIEMBRA
`
`TM manufactured by PALL CORPORATION.
`
`[0042] In general, a separator used in accordance with one or more embodiments of
`
`the present invention may be composed of material that may filter fiuid based on non-
`
`limiting, exemplary factors such as size, filter porosity (e.g., pour diameter), filter
`
`depth, or other factors that enhance high probability capture event with improved
`
`interconnected capillary system for superior capillary action without blockage. It
`
`should be noted that filter "depth" may be a function of networked tortuous path
`
`through which fluid may be traversed and hence, does not necessarily imply
`
`"thickness."
`
`[0043] It should be noted that it is only for convenience of example and discussion
`
`purposes that throughout the disclosure liquid source 180 (FIG. 1B) is indicated from
`
`a finger prick. It will be quickly apparent that any one of the one or more
`
`embodiments disclosed may use liquid source 180 to generate plasma that is not from
`
`a finger prick.
`
`[0044] FIGS. 1A to 1N are non-limiting, exemplary illustrations of various views of
`
`a plasma extraction device for extraction of plasma from a liquid sample in
`
`accordance with one or more embodiments of the present invention. FIG. 1A is a
`
`non-limiting, exemplary illustration of a plasma extraction device 100a inside a tube
`
`enclosure 102 in accordance with one or more embodiments of the present invention.
`
`As illustrated in FIG. 1A, plasma extraction device 100a with loaded plasma may be
`
`securely stored and dry—transported within tube 102 with a removable cap 104, with
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`tube 102 including marking (such as a bar code or QRTM code) 106 for tracking
`
`purposes.
`
`[0045] FIGS. 1B and 1C are non-limiting, exemplary illustrations of front and side
`
`views of plasma extraction device 100a, with FIG. 1D a sectional view of FIG. 1B in
`
`accordance with one or more embodiments of the present invention. As best
`
`illustrated in FIGS. 1B and 1C, users may remove plasma extraction device 100a out
`
`of tube 102, dip its absorbent probe 112 into a liquid source 180 (for example, from
`
`cut 182 of finger 184) to extract plasma from liquid sample, and place back plasma
`
`extraction device 100a securely within tube 102, enabling the liquid sample plasma to
`
`dry via vent holes 108 on tube 102 (shown in FIG. 1A), It should be noted that tube
`
`102 and cap 104 are adapted to be operated by well known automated instruments for
`
`plasma analysis and hence, need not be handled or operated by individuals.
`
`[0046] FIG. 1B is a non—limiting exemplary exploded view illustration of the various
`
`components of plasma extraction device 100a and tube 102 in accordance with one or
`
`more embodiments of the present invention. The exploded view shown in FIG. 1E
`
`illustrates disassembled, separated components that show the cooperative working
`
`relationship, orientation, positioning, and exemplary manner of assembly of the
`
`various components of plasma extraction device 100a and tube 102 in accordance
`
`with one or more embodiments of the present invention, with each component
`
`detailed below.
`
`[0047] Referring back to FIGS. 1B and 1C, plasma extraction device 100a is
`
`comprised of a handler assembly 130 and a plasma extractor module 110 that is
`
`detachably associated with handler assembly 130. Handler assembly 130 is
`
`comprised of a handler 132 that is adapted to be used with well known automated
`
`liquid handling instruments, and includes a dislodgement mechanism 152 for
`
`dismounting of plasma extractor module 110.
`
`[0048] As best illustrated in FIG. 1C and sectional view FIG. 1D, in this non-limiting,
`
`exemplary instance, handler 132 is a single piece unit. A first section 194 (including
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`first distal end 136) of handler 132 of handler assembly 130 may vary in design, is
`
`well known, and is disclosed in US. Patent Application publication US
`
`2013/0116597 to Rudge et a1. and US. Provisional Patent Application 62/149,415 to
`
`Emmet Welch, U.S. Non-Provisional Patent Application 15/ 130,373 to Emmet
`
`Welch, the entire disclosures of all of which are expressly incorporated by reference
`
`in their entirety herein. First section 194 is cylindrical and hollow 105 with top
`
`opening 188 and bottom opening 117. Second section 196 of handler 132 includes
`
`extension posts 198 that accommodate dislodgment mechanism 152 in between space
`
`103 and connect first section 194 to a third section 101. Second distal end 138 of
`
`handler 132 (at third section 101) is configured to detachably receive and hold the
`
`detachable plasma extractor module 110, and includes a generally, flat bottom end
`
`111 (best shown in FIG. 1F). It should be noted that handler 132 of handler assembly
`
`130 may be easily re—configured and adapted to operate with existing automated
`
`plasma instruments without departing from the scope of the invention and hence, the
`
`configuration of handler 132 of handler assembly 130 illustrated should not be
`
`limiting.
`
`[0049] As best illustrated in FIGS. 1F to II, plasma extractor module 110 is
`
`comprised of a housing 118 that includes a plasma extractor assembly. Plasma
`
`extractor assembly includes first absorbent member 112 (as the "probe") and hence,
`
`referred to as "absorbent probe 112," and a second absorbent member 116 (as the
`
`"reservoir" that holds the plasma) and hence, referred to as "absorbent reservoir 1 16."
`
`It should be noted that first and second absorbent members 112 and 116 may be
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`identical in all aspects, including form-factor. Alternatively and as illustrated, they
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`may also be different in form or, comprised of different materials, etc. Non-limiting,
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`non-exhaustive listing of examples of materials for absorbent member may comprise
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`of pores plastic, ceramic, carbon, etc. so long as the absorbent members are highly
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`hydrophilic or chemically changed to become hydrophilic. Non-limiting, non-
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`exhaustive listing of examples of absorbent members that may be used within one or
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`more embodiments of the present invention as absorbent probe/reservoir may include
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`those that are disclosed in US. Patent Application Publication 2013/01 16597 to
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`Rudge et al., US. Provisional Patent Application 62/149,415 to Emmet Welch, US.
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`Non-Provisional Patent Application 15/130,373 to Emmet Welch, and US
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`Provisional Patent Application 62/143,696 to Gijbertus G. Rietveld, U.S. Non-
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`Provisional Patent Application 15/048,859 to Gijbertus G. Rietveld, the entire
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`disclosures of all of which are expressly incorporated by reference in their entirety
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`herein. As further illustrated in FIGS. 1F to II, the plasma extractor assembly further
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`includes a well known separator 114 (e.g., VIVID PLASMA SEPARATION
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`lVEEMBRANE from PALL CORPORATION) positioned in between absorbent probe
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`112 and absorbent reservoir 116.
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`[0050] Absorbent probe 112 is physically mounted onto housing 118, with a first side
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`120 of absorbent probe 112 physically pressed against and contacting a first side 140
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`(FIGS. 1F and 1G) of separator 114. As best illustrated in FIGS. 1F, 1H-1 and 1H-2
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`housing 118 includes a periphery 148 with internal annular protuberance or flange
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`107 that is adapted to detachably couple with (e.g., detachably "snap" or press—fit
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`within) receiving recess 150 of second distal end 138 of handler 132 to thereby
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`detachably secure the plasma extractor assembly as the illustrated plasma extractor
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`module 110 with handler assembly 130. Absorbent probe 112 is simply friction (or
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`press) fit within opening 109 of housing 118, as shown in FIG. 1H-2.
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`[0051] Referring to FIGS. 1F and 1G, absorbent reservoir 116 has a first side 142
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`pressed against second side 144 of separator 114. In general, absorbent reservoir 116
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`is annular, with an opening 146 for operation of dislodgement mechanism 152. As
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`indicated above, absorbent reservoir 1 16 may be comprised of any shape, including
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`polygonal configurations, but optimally, it is best if absorbent reservoir 116 is
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`configured commensurate to the shape of separator 114 for maximum contact surface
`are a.
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`[0052] Both absorbent reservoir 116 and separator 114 may have complementary
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`undulating surfaces to maximize surface-to-surface contact area without increasing
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`the diameter of either absorbent members 112 and 116 or separator 114. In fact,
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`aspects that would increase or maximize surface-to-surface contact area would
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`improve efficiency and robustness (durability) of the entire system in terms of
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`extracting the maximum amount of plasma.
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`[0053]
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`In operation, fluid sample may first be collected by absorbent probe 112 from
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`liquid sample source 180 (FIG. 1B), and through capillary action fixed, predetermined
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`quantity of plasma is collected and loaded onto absorbent reservoirs 116. Thereafter,
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`plasma extraction device 100a, which now includes handler assembly 130 with
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`plasma extractor module 110 (with plasma loaded absorbent reservoir 116) may be
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`placed back into tube 102 (as shown in FIG. 1A) and transported dry to a lab on a
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`well known tube tray (not shown) for automated analysis. Non-limiting examples of
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`modes of drying may include desiccant or leaving to dry on the bench before
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`shipping. Well known automated liquid sample handling instruments may than be
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`used to automatically pick and uncap tube 102, and actually lift plasma extraction
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`device 100a via top distal end 136 of handler 132 of handler assembly 130.
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`Thereafter, plasma extractor module 110 may be dislodged from handler assembly
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`130 (FIGS. 1K-1 and 1K-2) by the automated liquid handling instruments but with the
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`dry plasma loaded absorbent reservoir 116 intact and still associated with handler
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`assembly 130. Once dislodged, the automated plasma analysis instruments then eject
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`the dry plasma loaded absorbent reservoir 116 (FIG. 1K-2) onto well known analysis
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`tray (FIG. 1N) for analysis of the dried plasma in well-known manner.
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`[0054] FIGS. 1K-1 to 1K-3 are sectional views of the lower end of handler assembly
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`130 taken from FIG. 1B. As best illustrated in FIGS. 1K-1 to 1K-3, in this non-
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`limiting exemplary instance, handler assembly 130 has dislodgement mechanism 152
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`in the form of an ejection pin (or plunger) that may be moved along a linear
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`reciprocating path 154, parallel a longitudinal axis 156 (FIG. 1B) of handler 132 of
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`handler assembly 130 manually or by well known automated liquid sample handling
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`instruments. Ejection pin 152 is comprised of a first engaging surface 158 for
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`ejecting plasma extractor module 110 (but without absorbent reservoir 116), and a
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`second engaging surface 160 for ejecting absorbent reservoir 1 16.
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`In other words, as
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`shown in FIGS. 1K-1 and 1K-2, ejection pin 152 first ejects (pushes out or away)
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`absorbent probe 112, housing 118, and separator 114 of plasma extractor module 110,
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`while absorbent reservoir 116 continues to remain mounted on handler assembly 130.
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`Once handler assembly 132 and remaining absorbent reservoir 116 are brought
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`aligned with an analysis tray 1 15 by a well known automated instrument (FIG. 1N),
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`ejection pin 152 is moved again (best shown in FIG. 1K-3) along linear reciprocating
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`path 154 where second engagement surface 160 contacts and pushes top surface 113
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`of absorbent reservoir 116 (near periphery of opening 146) to eject absorbent
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`reservoir 116 onto known tray 115 (as best illustrated FIG. 1N). It should be noted
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`that as is well known, the automated plasma analysis instruments may handle multiple
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`plasma loaded extraction devices and handler assemblies 132 simultaneously.
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`[0055] Accordingly, the automated plasma analysis instrument may move ejection
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`pin 152 to a first position (within chamber 190 - FIGS. 1K-1 and 1K-2) to enable first
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`engagement surface 158 to engage and dislodge absorbent probe 112, housing 118,
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`and separator 114. As shown in FIG. 1K—3, ejection pin 152 is also moved to a
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`second position (again by the automated liquid handling instruments) to enable
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`second engagement surface 160 to eject absorbent reservoir 116. Ejection pin 152
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`and its operation may be thought of as a two-stage plunger operation, with first stage
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`(FIGS. 1K-1 and 1K-2) releasing or dislodging absorbent probe 112, housing 118, and
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`separator 114, and second stage (FIG. 1K-3) dislodging absorbent reservoir 116. FIG.
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`1L is a non-limiting, exemplary illustration of a handler assembly 130 with plasma
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`extractor module 110 dismounted in accordance with the present invention.
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`[0056] FIGS. 1M-1 and 1M-2 are non-limiting, exemplary illustrations of a
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`dislodgement mechanism in accordance with one or more embodiments of the present
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`invention. As illustrated, dislodgement mechanism (or ejection pin 152) is comprised
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`of single piece unit comprised of a first section 162 with a first diameter 164 and a
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`second section 166 with a second diameter 168 that is wider than first diameter 164.
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`As shown, second engagement surface 160 (defined by diameter 168) has a larger
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`expanse than a diameter 170 (FIG. 11) of opening 146 of absorbent reservoir 116,
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`whereas first engagement surface 158 is a smaller with smaller diameter 164 and
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`hence, passes through opening 146 of absorbent reservoir 116. Well known automated
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`plasma analysis instrument moves pin 152 by griping groove 172 at top distal end 174
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`of pin 152.
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`[0057] Plasma extractor module l 10 enables extraction and loading of fixed,
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`predetermined quanti