WO2013089658A1 - Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire - Google Patents

Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire Download PDF

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Publication number
WO2013089658A1
WO2013089658A1 PCT/US2011/001982 US2011001982W WO2013089658A1 WO 2013089658 A1 WO2013089658 A1 WO 2013089658A1 US 2011001982 W US2011001982 W US 2011001982W WO 2013089658 A1 WO2013089658 A1 WO 2013089658A1
Authority
WO
WIPO (PCT)
Prior art keywords
pipette
assembly
vacuum passage
barrel assembly
axial
Prior art date
Application number
PCT/US2011/001982
Other languages
English (en)
Inventor
Paul J. Taylor
Original Assignee
Taylor Paul J
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taylor Paul J filed Critical Taylor Paul J
Priority to PCT/US2011/001982 priority Critical patent/WO2013089658A1/fr
Publication of WO2013089658A1 publication Critical patent/WO2013089658A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D19/00—Instruments or methods for reproduction or fertilisation
    • A61D19/04—Instruments or methods for reproduction or fertilisation for embryo transplantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/30—Surgical pincettes without pivotal connections
    • A61B2017/306—Surgical pincettes without pivotal connections holding by means of suction

Definitions

  • the present method and device relates to a method and device for manipulating the contents of a vesicular object having a size typically in the neighborhood of 100-300 microns.
  • This method and device has particular application for manipulation of the contents of mammalian embryos at the hatched blastocyst stage of development. This has not been possible with any previous device.
  • blastocysts are spherical vesicular structures consisting of a thin double layer of living cells surrounding a relatively large central cavity that is filled with an aqueous fluid.
  • the difficulty, and the failure of the prior art arises because of the physical characteristics of the envelope of these living cells which is flimsy but very resistant to puncture. For example, trying to inject material into a hatched blastocyst often simply pushes in the membrane without puncturing it, or conversely, ends up destroying the integrity of the membrane altogether. This compression can be severe and potentially damaging to the living cells. With the present device there is no compression at all.
  • the present method and device overcomes the above-described difficulties by providing a method and device which, using vacuum, firmly holds a portion of the surface of the blastocyst prior to piercing. Due to the method and device's unique double vacuum passages, fluid can be injected into a vesicular object while contained fluid is simultaneously, and rapidly, extracted from it. This rapid extraction provides the additional benefit of allowing the object's total volume to be held constant, preventing damage to early embryos that cannot tolerate complete collapse. As used herein, use of the word "fluid" includes any solids, including for example, DNA or other genetic material, associated with that fluid.
  • the method and device provides secure holding of a portion of the surface, especially the surface of a hatched blastocyst, for injection into the central volume of liquid, or reduction of that central volume, either through the pipette or around the pipette through the opening in the distal end of the inner tip.
  • the method and device allows for the above-described procedures to be done with the widely available stereoscope thereby expanding the number of facilities capable of performing many procedures.
  • Fig. 1 is a perspective view of the device
  • Fig. 2 is an elevational exploded view of the components of the barrel assembly used with the present device
  • Fig. 3 is an enlarged cross-section view of a barrel assembly used with the present device
  • Fig. 4 is a perspective view of the barrel assembly used with the present device
  • Fig. 5 is an enlarged elevational view of the vacuum jacket and outer tip
  • Fig. 6 is an enlarged cross-sectional view of the assembled vacuum jacket and outer tip shown in Fig. 5;
  • Fig. 7 is an assembly diagram of the components of the device shown in Fig. i ;
  • Fig. 8 is an enlarged cross-section of the device shown in Fig. 1 ;
  • Fig. 9 is a detail view at "A" shown in Fig. 8.
  • Fig. 10 is a detail view at "B" shown in Fig. 8;
  • Fig. 1 1 is a detail cross-sectional view of the distal end of the device (the tip) shown in use, with the pipette withdrawn.
  • Fig. 12 is a detail cross-sectional view of the distal end of the device (the tip) shown in use, with the pipette advanced and having pierced a vesicular object.
  • a device for performing micro-operations on a vesicular object is shown in Fig. 1.
  • the device in addition to a pipette (27) capable of injection and aspiration through an opening in its distal end (28), the device includes two separate generally cylindrical assemblies.
  • the first assembly is an outer assembly (1) and the second assembly is a barrel assembly (9).
  • the barrel assembly (9) is inserted into the outer assembly (1) as shown in Fig. 7.
  • the outer assembly comprises a vacuum jacket and an outer tip.
  • Fig. 5 The vacuum jacket (2) includes a main body portion open at both ends.
  • a conical outer tip, Fig. 5 (7) is frictionally fitted at one end of the vacuum jacket (2) as shown in
  • the vacuum jacket (2) is provided with external threads Fig. 5 (1 1) at its proximal end, for threadably engaging internal threads Fig. 3 (14) provided inside a rotatable coupling Fig. 2 (12) such coupling being attached to the upper barrel Fig. 2 (10) by means of external threads (1 1) on the upper barrel (10).
  • the knurled outer surface (13) of the coupling (12) allows the user to easily thread the barrel assembly (9) into the vacuum jacket Fig. 7.
  • the vacuum jacket is also provided with a radial vacuum port Fig. 6 (3) and an axial vacuum port (4) both of which extend through the wall of the vacuum jacket (2). These vacuum ports provide fluid communication to the interior of the vacuum jacket.
  • the barrel assembly Fig. 4 (9) includes an upper barrel (10), a lower barrel (18), a rotatable coupling (12), a spring-energized inner seal positioned between the upper and lower barrel Fig. 3 (17), a ferrule (25), and an inner tip (26).
  • the upper barrel (10) is provided with a blind bore for threadably
  • the lower barrel (18) has external threads (16) for mating with internal threads (15) located within the blind bore provided at the distal end of the upper barrel (10) as shown in Fig. 3.
  • the proximal end of the lower barrel has, inside its threaded end, a blind bore for seating of the inner seal (17).
  • Both the lower barrel (18) and the Upper barrel (10) are provided with co-aligned axial bores forming a central bore. Fig 3. (33).
  • a pipette Fig. 7 (27) is slidably received by the axial bores.
  • the axial bores are sized to leave an axial vacuum passage Fig. 10 (29) between the pipette (27) and the lower barrel (18).
  • Fig. 10 Such axial vacuum passage extending along the pipette and terminating at the secondary aperture.
  • the pipette (27) includes a tapered needle end and opening (28) at its distal end.
  • a spring- energized lip seal, the inner seal (17), is used to seal the lower barrel (18) against the pipette (27).
  • the distal end of the lower barrel (18) is further provided with a cylindrical portion having a reduced outside diameter as shown in Figs. 2 and 3. The outside diameter of the cylindrical portion is less than the inside diameter of the outer tip (7) as shown in Fig. 10 to provide a radial vacuum
  • the distal end of the lower barrel (18) is a metal nipple (24) designed to fit, via self-locking taper, into a stopped bore at the proximal end of a plastic ferrule Fig. 2 (25).
  • the proximal end of the inner tip (26) is frictionally fitted into a stopped bore at the distal end of the ferrule (25) as detailed in Fig. 2 and 3.
  • the inner tip (26) open at both ends, functions as a guide when the needle end (28) of pipette is extended through the secondary aperture at the distal end of the inner tip Fig. 1 1 (32).
  • the ferrule Fig. 2 (25) provides a positive seal between the lower barrel nipple Fig. 2 (24) and the inner tip (26) while also providing a flexible joint to insure the inner tip (26) can align concentrically within the primary aperture (8) of the outer tip Fig. 8 (7) during use.
  • the lower barrel (18) is also provided with grooves (19) and (22) as shown in Fig. 2 for receiving O-rings (20) and (23) as shown in Fig. 8.
  • the lower barrel (18) is also provided with a shunt Fig. 8 (21) that places the axial vacuum port (4) in fluid communication with the portion of the axial vacuum passage (29) surrounding the pipette (27).
  • Fig. 10 a shunt Fig. 8 (21) that places the axial vacuum port (4) in fluid communication with the portion of the axial vacuum passage (29) surrounding the pipette (27).
  • a vesicular object such as an embryo or other vesicular structure.
  • the barrel assembly (9) is inserted through the opening in the proximal end of the outer assembly (1) and, by rotation, the threaded coupling (12) on the barrel assembly is used to advance or withdraw the distal end of the inner tip (26) in relation to the distal end of the outer tip to form the desired contour of the holding well (31) as shown in Fig. 1 1.
  • a pipette (27) is slidably inserted through the bores provided in the barrel assembly (9), passing through the inner seal (17).
  • the pipette (27) is slidably adjusted so that the needle end (28) of the pipette (27) is slightly retracted from the inner tip opening, the secondary aperture (32).
  • Fig. 1 1.
  • a vesicular object, such as a blastocyst, is positioned immediately in front of the primary aperture (8) of the outer tip (7) as shown in Fig. 12.
  • a vacuum source (not shown) is connected to the radial vacuum port
  • radial vacuum passage (30) securely holds the vesicular object within the holding well formed at the primary aperture (8).
  • the final position of the inner tip (26) may then be advanced or withdrawn as needed to produce the desired relation with the surface of the vesicular object using the threaded coupling (12) so that the inner tip rests against, and seals against, the secured object.
  • Fig. 12. At which point the vacuum in passage (30) acts only on the ring of the vesicular object's surface in the area (30) between the distal end of the inner tip (26) and the distal end of the outer tip (7).
  • Vacuum can be applied to the axial vacuum port (4) and thereby to axial vacuum passage (29), to draw the exact point of penetration of the vesicular object surface tightly against the secondary aperture (32) in the distal end of the inner tip at the moment of penetration. Fig. 12.
  • the needle end (28) of the pipette (27) may then be slidably extended to pierce the outer surface of the vesicular object. Fig. 12.
  • Fluid can then be injected into, or aspirated from, the vesicular object through the pipette (27).
  • Vacuum can be applied to the axial vacuum port Fig. 8 (4) and thereby to axial vacuum passage (29), to draw fluid from the central volume of the object through the secondary aperture (32), that is, from between the inside of the inner tip (26) and the outside of the needle end (28) of the pipette (27). Fig. 12.
  • Another effect of the vacuum applied to the axial vacuum port (4) is to draw the external surface of the vesicular object taut across the secondary aperture (32), and allow for easy puncture with the needle end (28) of the pipette (27) as shown in Fig. 12.
  • This apparatus has particular advantage when working with a hatched blastocyst where the external surface of the embryo is very flimsy so it cannot be held on one side and punctured from the opposite side.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Transplantation (AREA)
  • Reproductive Health (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un procédé pour effectuer des micro-opérations sur un objet vésiculaire comprenant les étapes consistant à fixer l'objet vésiculaire par application d'une pression négative dans un passage de vide radial, faire avancer une pipette dans l'objet vésiculaire à travers un passage de vide axial, s'assurer que le passage de vide axial et le passage de vide radial ne sont pas en contact fluidique l'un avec l'autre, réguler la pression négative dans les passages de vide axial et radial et la pression ou le vide dans la pipette séparément, en permettant ainsi le maintien simultané de l'objet vésiculaire par application d'une pression négative dans le passage de vide radial, injecter dans ou aspirer de l'objet vésiculaire par la pipette, et aspirer de l'objet vésiculaire par application d'une pression négative dans le passage de vide axial.
PCT/US2011/001982 2011-12-14 2011-12-14 Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire WO2013089658A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2011/001982 WO2013089658A1 (fr) 2011-12-14 2011-12-14 Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2011/001982 WO2013089658A1 (fr) 2011-12-14 2011-12-14 Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire

Publications (1)

Publication Number Publication Date
WO2013089658A1 true WO2013089658A1 (fr) 2013-06-20

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/001982 WO2013089658A1 (fr) 2011-12-14 2011-12-14 Procédé et dispositif pour effectuer des micro-opérations sur un objet vésiculaire

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WO (1) WO2013089658A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6592552B1 (en) * 1997-09-19 2003-07-15 Cecil C. Schmidt Direct pericardial access device and method
US20090023206A1 (en) * 2007-07-18 2009-01-22 Fujitsu Limited Microinjection apparatus and method of injecting fluid
WO2009079474A1 (fr) * 2007-12-14 2009-06-25 The University Of North Carolina At Chapel Hill Procédés, systèmes et supports lisibles par ordinateur pour faciliter l'automatisation de la micro-injection de blastocystes
US20110212521A1 (en) * 2009-12-23 2011-09-01 Eppendorf Ag Apparatus and Method for Generating a Tool Motion

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6592552B1 (en) * 1997-09-19 2003-07-15 Cecil C. Schmidt Direct pericardial access device and method
US20090023206A1 (en) * 2007-07-18 2009-01-22 Fujitsu Limited Microinjection apparatus and method of injecting fluid
WO2009079474A1 (fr) * 2007-12-14 2009-06-25 The University Of North Carolina At Chapel Hill Procédés, systèmes et supports lisibles par ordinateur pour faciliter l'automatisation de la micro-injection de blastocystes
US20110212521A1 (en) * 2009-12-23 2011-09-01 Eppendorf Ag Apparatus and Method for Generating a Tool Motion

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WANG ET AL., A FULLY AUTOMATED ROBOTIC SYSTEM FOR MICROINJECTION OF ZEBRAFISH EMBRYOS, September 2007 (2007-09-01), pages E862 *

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