EP0612403B1 - Verbindungstyp-vorrichtung für mikrolitermengen - Google Patents

Verbindungstyp-vorrichtung für mikrolitermengen Download PDF

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Publication number
EP0612403B1
EP0612403B1 EP92925198A EP92925198A EP0612403B1 EP 0612403 B1 EP0612403 B1 EP 0612403B1 EP 92925198 A EP92925198 A EP 92925198A EP 92925198 A EP92925198 A EP 92925198A EP 0612403 B1 EP0612403 B1 EP 0612403B1
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EP
European Patent Office
Prior art keywords
microtube
membrane
connector assembly
open end
connector
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EP92925198A
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English (en)
French (fr)
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EP0612403A1 (de
EP0612403A4 (de
Inventor
Yuan Chuan Lee
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Artchem Inc
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Artchem Inc
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56—Labware specially adapted for transferring fluids
    • B01L3/565—Seals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021—Test tubes specially adapted for centrifugation purposes

Definitions

  • the present invention relates to a dual invertible microtube and connector assembly for micro solutions capable of performing efficient and continuous transfer and/or treatment of a small amount of sample solution.
  • an instrument such as for example a micropipet, is used to transfer the sample solution from the reaction tube into another device for ultrafiltration.
  • a certain amount of loss of the sample is inevitable in the process of transferring the sample solution. The loss is greater when the sample quantities are smaller.
  • a protein may be labeled using radioisotopes, and then the labeled protein constituent and the isotopes should be separated.
  • the invention comprises an assembly as claimed in claim 1 or claim 5.
  • the present invention permits simultaneous transfer of a sample solution between containers as well as a predetermined treatment of the solution using two containers and a specially adapted connector assembly for connecting these containers. Accordingly, use of transferring instruments, such as a micropipet, are not required, and the problems of sample loss and contamination risk are substantially reduced or minimized.
  • Fig. 1 is a schematic diagram of a connection-type transfer and treatment system and method for micro solutions.
  • Fig. 2 is partial sectional view illustrating a specific structure of a centrifugal connection-type micro solution transfer and treatment device constructed in accordance with a first embodiment of the present invention.
  • Figs. 3a-3b is a series of diagrams illustrating the structure of the tube 10 shown in Fig. 2.
  • Figs. 4a-4b is a series of diagrams illustrating structure of the dual tube connector 16 shown in Fig. 2.
  • Fig. 5 is a four part series diagram illustrating structure of the filter element supporting member 22 shown in Fig. 2.
  • Figs. 6a-6b is a series of diagrams illustrating structure of the stopper 34 shown in Fig. 2.
  • Fig. 7 is partial sectional view of a centrifugal connection-type micro solution transfer and treatment system constructed in accordance with a second embodiment of the present invention.
  • Fig. 8 is a partial section view of a tube of the second embodiment micro solution transfer/treatment device of Fig. 7 shown here provided with a screw-on cap 122.
  • Fig. 9 is a cross-sectional exploded view of the second embodiment micro solution transfer/treatment device of Fig. 7 shown with the upper or source tube 110b omitted.
  • Fig. 10 is a top end view of the stopper 150 of the second embodiment micro solution treatment device of Fig. 7 taken along the line and in the direction of arrows 10-10 of Fig. 9.
  • Fig. 11 is an isometric view of the stopper 150 of the second embodiment device of Fig. 7.
  • Fig. 11a is a perspective view of a tool 162 for inserting the stopper 150 into the inner cylinder 130 of the connector 126.
  • Fig. 12 is a top end view of the connector 126 of the second embodiment micro solution treatment device illustrating the membrane support region of the connector.
  • Fig. 13 is a fragmentary cross section view of the membrane support region of the connector of the second embodiment micro solution treatment device taken along the line and looking into the direction of arrows 13-13 of Fig. 12.
  • Fig. 14 is a side elevation view of an adapter 170 used for securing the second embodiment for the microsolution treatment device of the present invention in a centrifuge rotor.
  • Fig. 15 is a side elevation view in cross section of the adapter 170 of Fig. 14.
  • Fig. 16 is an isometric view illustrating how the second embodiment micro solution treatment device fits within the adapter (shown in cross-section).
  • Fig. 17 is a functional schematic view in partial cross-section of the second embodiment micro solution treatment device of the present invention held by the adapter and positioned in a fixed angle rotor.
  • Fig. 1 is a diagram which describes in schematic fashion the overall system principles and method steps for the connection-type micro solution transfer and treatment system and method of the present invention.
  • the presently preferred embodiments of the present invention relate to a treatment system and method for pretreatment of solutions for high performance liquid chromatography (HPLC) using an ultrafiltration membrane.
  • HPLC high performance liquid chromatography
  • a researcher first carries out a predetermined chemical reaction such as, for example, an enzyme reaction, in a container or tube A schematically shown in Fig. 1 (a).
  • the resulting solution or product is designated by oblique lines in Fig. 1.
  • a cap (not shown) may be used on the open end of the tube.
  • Fig. 1 (b) At the end of the reaction, the experimenter then removes a cap (not shown) from tube A and attaches one end of a connector C to the tube A opening.
  • a second container indicated in the drawing as container or tube B, having substantially the same shape as tube A, is connected in upside-down fashion to the other side of the connector C.
  • the connector C includes an ultrafiltration membrane (not shown) therein.
  • tube A is referred to as the "source tube” or “reaction tube” and tube B is referred to as the "target tube”.
  • the sample solution inside reaction (source) tube A passes through the ultrafiltration membrane included inside connector C into the target tube B. Molecules, stripped of solvent, having predetermined or larger molecular weights are trapped by the ultrafiltration membrane.
  • the centrifugation is executed with the reaction tube containing the sample solution and the tube for the centrifugation treatment being integrally connected with the connector having an ultrafiltration membrane therein. Therefore, by eliminating the need for use of a micropipet to transfer the solution between source and target tubes, there is no solution loss due to solution remaining in the micropipet instrument. Also, possible contamination of the pipet is avoided. Further, as compared to when solution transfer is performed by a "direct pour" method whereby the contents of the reaction (source) tube are poured into the target tube, virtually no sample solution residue remains on the inner source tube wall in the present invention in view of the completeness afforded by filtration through centrifugation.
  • the treatment in the above figures 1 (a) - (d) may be repeated in each step after the second step using tube B (originally the target tube), now containing the filtered solution (Fig. 1 (d)), as the new reaction (source) tube A', and adding a new target tube B', and so on.
  • Fig. 2 is a partial sectional view of a micro solution transfer/treatment system apparatus constructed in accordance with a first embodiment of the present invention.
  • the micro solution treatment system apparatus 1 is illustrated in a connected state corresponding to the schematic representations of Figs. 1 (c) and (d).
  • the micro solution treatment system apparatus 1 comprises reaction or source tube 10a and target tube 10b, each having an open end 12a, 12b oriented opposed facing one another and joined together by a connector assembly 16.
  • the tubes 10a, 10b are similarly shaped and are preferably fabricated from a known plastic material of the type commonly used in micro-centrifuge applications, such as for example, polypropylene or polyethylene.
  • the tubes 10a, 10b correspond to the tubes A and B of Fig. 1, respectively, and the connector assembly 16 corresponds to the connector C of Fig. 1.
  • the connector assembly 16 comprises a connector member 17, a membrane support 22, and a stopper 34.
  • the connector member or connector 17 is provided with two different connector ends for engagement with the tube openings 12a, 12b of the respective tubes 10a, 10b including a first connector end 18 defined as an open mouth-type member having tapered receiving inner walls 19 dimensioned for snug, slip-fit engagement with an outer peripheral wall 14a, 14b of a corresponding tube opening 12a or 12b, and a second connector end 20 having a male screw portion 19 provided along its outer peripheral wall for engagement with a corresponding female screw portion 15a, 15b provided to an inner peripheral wall of a corresponding tube opening 12a, 12b.
  • a first connector end 18 defined as an open mouth-type member having tapered receiving inner walls 19 dimensioned for snug, slip-fit engagement with an outer peripheral wall 14a, 14b of a corresponding tube opening 12a or 12b
  • a second connector end 20 having a male screw portion 19 provided along its outer peripheral wall for engagement with a corresponding female screw portion 15
  • the connector 17 is shown having its first connector end 18 fitted over the outer peripheral wall 14a of tube opening 12a of the source tube 10a, while the male screw portion 19 of the second connector end 20 threadingly engages the inner female screw portion 15b of tube opening 12b of the target tube 10b.
  • the membrane support 22 is provided with a male screw portion 24 formed along an outer peripheral wall and having threads sized for receivingly engaging the threads of the inner peripheral wall female screw portions 15a, 15b of a tube opening 12a, 12b.
  • the outer peripheral wall male screw portion 24 of membrane support 22 engages the inner peripheral wall female screw portion 15a of the source tube opening 12a.
  • the membrane support 22 is adjusted for receiving an ultrafiltration membrane 30 placed along a bottom supporting surface 26 thereof (See Fig. 5).
  • a stopper 34 is provided for ensuring that the membrane remains fixed within the membrane support 22.
  • Fig. 3 is an enlarged two view diagram showing in more detail the structure of the tube 10.
  • tube 10 may be either source tube 10a or target tube 10b.
  • part (a) is a plan view of the tube 10 looking into the tube opening 12
  • part (b) is a cross-section view showing the flat outer peripheral wall 14 and female screw portion inner peripheral wall 15 of the tube opening 12.
  • the wall thickness "t" of the tube opening 12 preferably tapers slightly towards its free end to permit ease of insertion within the receiving connector end 18 of the connector member 17.
  • Fig. 4 is an enlarged two view series diagram showing structure of the connector 17 of Fig. 2 wherein part (a) is a plan view and part (b) is a cross-section view.
  • the connector 17 is generally circular in cross section and includes an inner stop surface or ledge 19 against which end portions of the tube opening 12 and membrane support 24 are constrained in abutting engagement when the system apparatus 1 is fully connected together (see Fig. 2).
  • the connector 17 is provided with a central bore hole 23 for permitting transfer of solution material from a first tube to a second tube connected thereto.
  • Fig. 5 is an enlarged four view series diagram illustrating the structure of the membrane support member 22 of Fig. 2 wherein part (a) is a top plan view (supporting surface 26 omitted); part (b) is a cross sectional view; part (c) is a side elevation view; and part (d) is an enlarged bottom plan view showing the configuration of a plurality of through holes or ducts 28 formed in the bottom wall 26 shown in part (a). Note, for purposes of clarity, the ducts 28 are not shown in the cross sectional view of part (b).
  • Fig. 6 is a two view series diagram illustrating structure of tubular stopper 34 of Fig. 2 wherein part (a) is a side elevation view, and part (b) is a top plan view.
  • Stopper 34 resembles a ring or tubular member and includes a circumferential rib 36 provided on its outer peripheral wall 38 which is adapted for snap fit insertion within a corresponding convex groove 27 provided to the inner peripheral wall 29 of the membrane support 22 (see Fig. 5).
  • Combination of two tubes 10a and 10b as described above can simultaneously achieve efficient transfer of solutions and the centrifugation treatment as shown in Fig. 1.
  • Figs. 7-13 illustrate a second embodiment for the microsolution/transfer treatment system apparatus of the present invention which is designated generally as element 100 in the drawings.
  • the second embodiment 100 for the microsolution treatment system apparatus comprises two similarly shaped containers or tubes 110a, 110b each having an open end 112a, 112b which in use are connected together by a connector assembly 126.
  • the connector assembly 126 of the second embodiment comprises two principle elements including a connector/filter retainer member 127 and a stopper 150.
  • the connector member 127 is formed as a bi-annular structure having an outer perimeter cylindrical shell portion or sleeve 128 surrounding an inner cylinder portion 130 and connected integrally thereto by a lateral, radially extending web 132.
  • the outer shell (sleeve) 128 and inner cylinder define two connector ends including a first threaded connector end 136 and a second slip-on connector end 140.
  • the outer shell portion or sleeve 128 is preferably serrated or knurled at 137 to facilitate handling by a user. Similar grip facilitating surfaces 120a, 120b may be provided to the outer surfaces of the tubes 110a, 110b.
  • the threaded connector end 136 includes female screw threads disposed along an inner peripheral wall of the outer cylindrical portion 128 adapted to engage the male screw threads 114a disposed along the outer peripheral wall of the tube opening 112a of tube 110a.
  • the slip on connector end 140 fits over the open end 112b (and the male threads 114b) of the target tube 110b.
  • the inner cylinder portion 130 of the connector 127 also includes a transverse membrane support surface or region 134. In use, the connector member 127 is attached to the tube opening such that the membrane supporting inner cylinder 130 is oriented to fit within the tube opening 112b of the target tube 110b.
  • the membrane support surface 134 of the inner cylinder 130 defines a foramenous plate on which the ultrafiltration membrane 156 rests. The ultrafiltration membrane 156 is tightly held in place by a stopper 150 which fits within the inner cylinder 130 during use.
  • the preferred height dimension of the wall for the tubular stopper 150 and inner cylinder 130 is sufficiently high to ensure that all solution remains within the cylindrical volume defined by the bore of tubular stopper 150 during centrifuge operation such that a meniscus, which represents loss of solution, is not permitted to form above the stopper 150 or cylinder 130.
  • This volume or capacity is typically on the order of 500 ⁇ l to 600 ⁇ l for microsolution work.
  • the wall height of the stopper 150 is preferably slightly less than the surrounding wall portion of the inner cylinder 130 so that the inwardly tapered ends 158 of the stopper 150 form a gradual transition to promote full flow of fluid in the downward direction from the source tube into the target tube during centrifuge operation.
  • the end walls forming the mouth opening of the inner cylinder 130 are preferably provided with a slight chamfer at 166 (see Fig. 9) to further promote complete flow of fluid down into the inner cylinder 130.
  • Fig. 8 shows a single tube 110 having a screw top cap 122 for threading onto the outer male screw threads 114 of the tube opening 112.
  • the cap 122 includes an O-ring 124 to ensure against fluid loss.
  • the screw on cap 122 is useful for sealing a source tube 110a, such as for example after an enzyme reaction has occurred, or for sealing a target tube after the desired treatment for the microsolution has been obtained.
  • the stopper 150 includes plurality of notched relieved portions 160 spaced equidistant along the top perimeter wall 154. These notched portions 160 facilitate press fit insertion of the stopper within the inner cylinder membrane support 130 of the connector assembly 126.
  • the stopper 150 preferably includes a longitudinal groove (not shown) formed along its outer cylindrical wall to facilitate air exchange and thereby relieve any trapped air within the inner cylinder membrane support 130 and the stopper 150 when the stopper 150 is fitted within the membrane inner cylinder membrane support 130.
  • Fig. 11a illustrates an example tool 162 useful for inserting the stopper 150 within the inner cylinder 130.
  • the tool 162 preferably includes axially extending peripheral tab members 164 for engaging the notched relieved portion 160 of the tubular stopper 150.
  • the top perimeter edge 154 of the stopper 150 is preferably tapered at 158 to ensure that all microsolution drains towards the ultrafiltration membrane during use and does not get trapped above the stopper perimeter edge 154.
  • all the edges contours of the notches 160 are preferably rounded to promote and ensure fluid flow.
  • Figs. 12 and 13 illustrate in more detail the generally foramenous plate-like membrane support region 134 of the inner cylinder 130 of the connector 127.
  • the porous plate region 134 includes a plurality of arcuate and semi-arcuate through holes or ducts 142 interspaced by ribs or land portions 144.
  • the membrane's support region of foramenous plate 134 includes a slightly upraised rib member 146 having a peak disposed coordinately aligned with lower end wall 152 of the tubular stopper 150 when the stopper 150 is fitted within the inner cylinder 130. This is best seen with reference to Fig. 13 (stopper 150 and membrane 152 are indicated in phantom). In this way, the membrane 156 is maintained taut and prevented from moving by the engagement of the bottom end wall 152 stopper against the upraised rib member 146.
  • Figs. 14-16 show an adapter 170 which may be used for fitting the first or second embodiments of the microsolution transfer/treatment system 100 within a receiving socket of a centrifuge rotor.
  • the microsolution treatment system has a slightly increased outer radius as compared to conventional centrifuge tubes. Accordingly, a wider diameter socket in a centrifuge rotor is preferably provided for receiving the dual tube/connector system.
  • an adapter 170 is provided to ensure proper fit and support of the microsolution system 100 within the centrifuge rotor.
  • the adapter 170 is generally cylindrical in cross section and has an inner diameter sized for a close tolerance fit with the connection-type microsolution system when inserted in it.
  • the outer surface of the adapter 170 is provided with a laterally extended circumferential ledge member 174 (an annular flange), which acts as a stop member and rest support when fitted into a receiving socket 176 of a centrifuge rotor.
  • Fig. 17 shows the system apparatus 100 placed within the adapter 170 and inserted within an appropriate receiving socket or hole 176 of a rotor 178.
  • the adapter includes at its bottom end a reduced radius opening 180 sized to engage an outer portion of one of the tubes of the microsolution system 100 at a location along the bottom tube adjacent the connector assembly, such that the bottom end 182 of the system apparatus 100 is prevented from contacting a base portion 184 or side wall 185 of the centrifuge rotor 178.
  • the upstanding walls 186 of the adapter 170 above the ledge member 174 are of sufficient length to ensure adequate support of the connection-type microsolution treatment system apparatus during centrifuge operation.
  • the forward portion of the adapter may be cut away (indicated in phantom) at 188, thereby leaving only a high back supporting portion of the upper adapter walls above the annular flange or ledge member 174. (The cut away portion is indicated as element 171.) In this way, a lightweight adapter having sufficient support for reducing stresses placed on the system apparatus from centrifuged forces is achieved.
  • a pretreatment system utilizing affinity can be implemented by providing an affinity functional membrane in the connection.
  • the connector membrane may contain antibody or antigens and lectins or an ion-exchange membrane, or a membrane having other suitable functions.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)

Claims (10)

  1. Duale, invertierbare Mikroröhrchen- und Verbindungsbaugruppe zum Überführen und Behandeln von Mikrolösungen und zur Zentrifugation, enthaltend in wirkungsmäßiger Kombination:
    (a) ein erstes Quellmikroröhrchen (10a), das ein erstes offenes Ende (12a) aufweist und in einem zweiten, verjüngten, ständig geschlossenen Ende (12c) endet, welches erste Mikroröhrchen geeignet ist, eine Mikrolösungsprobe zur Behandlung durch Inversion aufzunehmen;
    (b) ein zweites Zielmikroröhrchen (10b), das im wesentlichen die gleiche Form wie das erste Mikroröhrchen hat und ein erstes offenes Ende (12b) aufweist und in einem zweiten, verjüngtem, ständig geschlossenen Ende (12c) endet;
    (c) wobei jedes der Mikroröhrchen neben seinem offenen Ende enthält:
    (c1) Gewinde (15a, 15b), die längs einer ersten Umfangswandfläche ausgebildet sind, und
    (c2) eine glatte, zylindrische zweite Umfangswandfläche (14a, 14b);
    (d) eine Verbindungsbaugruppe (16) zum Verbinden des offenen Endes des ersten Mikroröhrchens mit dem offenen Ende des zweiten Mikroröhrchens, welche Verbindungsbaugruppe ein mit Gewinde versehenes Verbindungsende (20) für einen Gewindeeingriff mit dem mit Gewinde versehenen offenen Ende eines des ersten oder des zweiten Mikroröhrchens aufweist, und
    (e) eine Membran (30), die innerhalb der Verbindungsbaugruppe vorgesehen ist und einer insgesamt flachen, durchlochten Membranstützfläche zugeordnet ist, so daß eine Flüssigkeit zwischen den beiden Mikroröhrchen nur durch die Membran hindurch strömen kann;
       dadurch gekennzeichnet, daß
    (f) das andere, insgesamt zylindrische Verbindungsende (18) der Verbindungsbaugruppe (16) mit einer glatten, inneren Umfangswandfläche (19) für eine Gleitpaßverbindung um eine äußere Umfangswand des offenen Endes des anderen des ersten oder zweiten Mikroröhrchens ausgebildet ist,
    (g) eine insgesamt rohrförmige Membranhalterung (22) eine äußere Umfangswand, eine innere Umfangswand und die insgesamt flache, durchlochte Membranstützfläche (26) aufweist, die innerhalb der inneren Umfangswand angeordnet ist, wobei die innere Umfangswand und die durchlochte Membranabstützung einen zentralen Hohlraum zum Einsetzen innerhalb des offenen Endes desjenigen Mikroröhrchens bilden, über das das erste Verbindungsende mit Gleitpassung geschoben ist;
    (h) eine einzige Einrichtung (34) zum Befestigen der Membran (30) an der durchlochten Fläche der Membranhalterung derart, daß eine Flüssigkeitsdichtung zwischen dem Umfang der Memranhalterung und der Membran geschaffen ist;
    (i) wobei die Membranhalterung in Verbindung mit der Befestigungseinrichtung die Membran in einem ausgesparten Abstand innerhalb des offenen Endes des einen des ersten oder zweiten Mikroröhrchens halten, um die Probenlösung zu filtern und sie einer vorbestimmten Behandlung zu unterwerfen, während die Probenlösung von dem ersten Quellmikroröhrchen in das zweite Zielmikroröhrchen gelangt, indem das erste Quellmikroröhrchen, das die zu filternde Probenlösung enthält, über das zweite Zielmikroröhrchen invertiert wird.
  2. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 1, wobei die Membranhalterung (22) längs einer äußeren Umfangswand Gewindegänge (24) für einen Gewindeeingriff mit Gewindegängen eines des ersten oder zweiten Mikroröhrchens (10a, 10b) enthält.
  3. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 2, wobei die Befestigungseinrichtung für die Membran ein Anschlagbauteil (34) in Form eines Rings ist, dessen Außenflächengestalt derart ist, daß er mit Schnappsitz in den zentralen Hohlraum der Halterung einsetzbar ist.
  4. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 3, wobei die Membran (30) eine Ultrafiltrationsmembran ist.
  5. Duale, invertierbare Mikroröhrchen- und Verbindungsbaugruppe zum Überführen und Behandeln von Mikrolösungen und zur Zentrifugation, enthaltend in wirkungsmäßiger Kombination:
    (a) ein erstes Quellmikroröhrchen (110a), das ein erstes offenes Ende aufweist und in einem zweiten, verjüngten, ständig geschlossenen Ende endet, welches erste Mikroröhrchen zur Aufnahme einer Mikrolösungsprobe geeignet ist;
    (b) ein zweites Zielmikroröhrchen (110b), das im wesentlichen die gleiche Gestalt wie das erste Mikroröhrchen hat und ein erstes offenes Ende aufweist und in einem zweiten, verjüngtem, ständig geschlossenen Ende endet;
    (c) wobei jedes der Mikroröhrchen neben seinem offenen Ende enthält:
    (c1) Gewinde (114a, 114b), die längs einer ersten Umfangswandfläche ausgebildet sind; und
    (c2) eine glatte, zylindrische zweite Umfangswandfläche;
    (d) eine Verbindungsbaugruppe (126) zum Verbinden des offenen Endes des ersten Mikroröhrchens mit dem offenen Ende des zweiten Mikroröhrchens, welche Verbindungsbaugruppe ein mit Gewinde versehenes Verbindungsende für einen Gewindeeingriff mit dem mit Gewinde versehenen offenen Ende eines des ersten oder zweiten Mikroröhrchens aufweist, und
    (e) eine Membran (30), die innerhalb der Verbindungsbaugruppe vorgesehen ist und einer insgesamt flachen, durchlochten Fläche derart zugeordnet ist, daß eine Flüssigkeit zwischen den beiden Mikroröhrchen nur durch die Membran hindurch strömen kann;
       dadurch gekennzeichnet, daß
    (f) die Verbindungsbaugruppe eine Einrichtung (130, 134, 124, 150) zum Halten der Membran (156) in einem ausgesparten Abstand innerhalb des offenen Endes des zweiten Mikroröhrchens enthält, um die Mikrolösungsprobe zu filtern und sie einer vorbestimmten Behandlung zu unterwerfen, während die Mikrolösungsprobe von dem ersten Quellmikroröhrchen in das zweite Zielmikroröhrchen gelangt, indem das erste Quellmikroröhrchen, das die zu filternde Probenlösung enthält, über das zweite Zielmikroröhrchen invertiert wird, und die Verbindungsbaugruppe enthält:
    (g) einen äußeren Hülsenbereich (128) mit einer Innenwand mit einem ersten, mit Gewinde versehenen Verbindungsbereich (136) für den Eingriff mit dem mit Gewinde versehenen offenen Ende des ersten Mikroröhrchens, und wobei ein zweiter Verbindungsbereich (140) der Wand eine glatte Fläche zum Gleiten über die Gewindegänge des Endes des zweiten Mikroröhrchens aufweist;
    (h) eine innere rohrförmige Membranhalterung (130), die ein erstes Ende aufweist, das integral an der Innenwand der äußeren Hülse befestigt ist, und ein zweites freies Ende aufweist, das unter Passung in das offene Ende des zweiten Mikroröhrchens einschiebbar ist, wobei das zweite Ende der inneren, rohrförmigen Membranhalterung die insgesamt flache, durchlochte Fläche (134) zur Aufnahme der Membran aufweist;
    (i) eine Einrichtung (150) zum Befestigen der Membran an der durchlochten Fläche der Membranhalterung und zur flüssigkeitsdichten Verbindung zwischen einem Umfang der Membranhalterung und der Membran und um ein Zurückhalten von Flüssigkeit in der Verbindungsbaugruppe und dem ersten Mikroröhrchen im wesentlichen auszuschalten.
  6. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 5, wobei die Befestigungseinrichtung für die Membran (150) ein insgesamt rohrförmiges Anschlagbauteil (150) aufweist, das unter Passung in die Membranhalterung (130) einsetzbar ist und eine Bodenstirnwand aufweist, die mit einem angehobenen, umlaufenden Rippenbauteil (145) ausgerichtet ist, das an der durchlochten Fläche (134) der Membranhalterung vorgesehen ist, um die Membran an der Membranhalterung zu befestigen.
  7. Duale, invertierbare Mikroröhrchen- und Verbindungsbaugruppe nach Anspruch 5 oder 6, dadurch gekennzeichnet, daß ein rohrförmiger Adapter (170) vorgesehen ist, der unter Eingriff wenigstens die Verbindungsbaugruppe (126) aufnimmt, um die duale Mikroröhrchen- und Verbindungsbaugruppe (110a, 110b, 126) innerhalb eines Zentrifugenrotors (178) geeignet zu positionieren, wenn das erste und das zweite Mikroröhrchen (110a, 110b) mittels der Verbindungsbaugruppe (126) verbunden sind.
  8. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 6 oder 7, dadurch gekennzeichnet, daß die Membran eine Ultrafiltrationsmembran (156) ist.
  9. Duale Mikroröhrchen- und Verbindungsbaugruppe für Mikrolösungsproben nach Anspruch 8, dadurch gekennzeichnet, daß die Ultrafiltrationsmembran (156) eine Komponente zum Behandeln der Lösung während ihres Durchtritts enthält.
  10. Baugruppe nach Anspruch 9, wobei das Reagenz ein Enzym enthält.
EP92925198A 1991-11-14 1992-11-13 Verbindungstyp-vorrichtung für mikrolitermengen Expired - Lifetime EP0612403B1 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US791837 1985-10-28
US79183791A 1991-11-14 1991-11-14
US93001792A 1992-08-13 1992-08-13
US930017 1992-08-13
PCT/US1992/009789 WO1993010433A1 (en) 1991-11-14 1992-11-13 Connection-type treatment system for micro solution and method of treatment

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EP0612403A1 EP0612403A1 (de) 1994-08-31
EP0612403A4 EP0612403A4 (de) 1994-12-28
EP0612403B1 true EP0612403B1 (de) 1999-02-03

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DE9418060U1 (de) * 1994-11-11 1996-03-14 SC - Sanguis Counting Kontrollblutherstellungs- und Vertriebs GmbH, 51588 Nümbrecht Probenröhre und Abschlußkappe, insesondere für Kapillar-Blutentnahme
US5603900A (en) * 1995-05-19 1997-02-18 Millipore Investment Holdings Limited Vacuum filter device
GB2321857B (en) * 1997-02-05 2000-05-24 Intersep Ltd Improvements in filters
DE10141817B4 (de) 2001-08-27 2005-03-03 Eppendorf Ag Membranvorrichtung zum Aufnehmen von Proben und Verfahren zur Herstellung einer Vorrichtung
US7456024B2 (en) 2001-08-29 2008-11-25 Hexal Pharma Gmbh Method and device for preparing a sample of biological origin in order to determine at least one constituent contained therein
EP2768594B1 (de) * 2011-10-18 2023-06-07 The Trustees of Columbia University in the City of New York Medizinische vorrichtung und verfahren zum sammeln biologischer proben
CN105122031B (zh) 2012-11-20 2019-02-01 纽约哥伦比亚大学董事会 医疗设备以及用于收集生物样本的方法
AU2016399224B2 (en) * 2016-03-23 2019-05-16 Husqvarna Ab Tap connector with flow stabilization
CN110146583B (zh) * 2019-04-26 2020-08-11 中国科学院地质与地球物理研究所 Carius管分解样品的方法和Re-Os同位素分析的方法

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DE69228386D1 (de) 1999-03-18
AU3135093A (en) 1993-06-15
EP0612403A1 (de) 1994-08-31
CA2123203A1 (en) 1993-05-27
TW209853B (de) 1993-07-21
DE69228386T2 (de) 1999-09-30
JPH07501150A (ja) 1995-02-02
EP0612403A4 (de) 1994-12-28

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