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WO2005115623A1 - Nano-canule - Google Patents

Nano-canule Download PDF

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Publication number
WO2005115623A1
WO2005115623A1 PCT/EP2005/004437 EP2005004437W WO2005115623A1 WO 2005115623 A1 WO2005115623 A1 WO 2005115623A1 EP 2005004437 W EP2005004437 W EP 2005004437W WO 2005115623 A1 WO2005115623 A1 WO 2005115623A1
Authority
WO
WIPO (PCT)
Prior art keywords
nanotube
carrier film
cannula
nano
instrument
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2005/004437
Other languages
German (de)
English (en)
Inventor
Michael Giersig
José ROJAS-CHAPANA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Stiftung Caesar Center of Advanced European Studies and Research
Original Assignee
Stiftung Caesar Center of Advanced European Studies and Research
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 Stiftung Caesar Center of Advanced European Studies and Research filed Critical Stiftung Caesar Center of Advanced European Studies and Research
Publication of WO2005115623A1 publication Critical patent/WO2005115623A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/0275Interchangeable or disposable dispensing tips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00Nanotechnology for materials or surface science, e.g. nanocomposites
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/003Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/023Adapting objects or devices to another adapted for different sizes of tubes, tips or container
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0896Nanoscaled

Definitions

  • the present invention relates to a cannula for an injection and / or an extraction instrument, in particular for a syringe or for a pipette, the instrument having a hollow needle and an adapter sealingly enclosing the hollow needle, and the adapter being designed such that it is for the purpose the holder interacts with corresponding receiving means of the instrument.
  • Such cannulas are traditionally known from medical practice and research, the dimensions of which are adapted to the respective application.
  • metal hollow needles of macroscopic dimensions are known to be used, which are placed, for example, on a piston syringe.
  • Hollow needles are also known for microscopic applications, most of which are drawn from glass and the tip of which has a diameter of a few micrometers. In extreme cases, even tips with a diameter of less than 0.1 micrometer can be manufactured with great effort.
  • Such micro-needles can be used for the targeted injection or removal of cell material as long as the biological objects, such as large ones Bacteria or oocytes that are larger than one and in particular several micrometers in size. Most bacteria and especially viruses are too small for such treatments.
  • the invention now has the task of creating a nano-cannula that can be manufactured easily and inexpensively in large quantities with relatively little technical effort and that is robust enough for use as a nano-syringe, nano-pipette, nano- Tweezers or nano-drills. It is also an object of the invention to provide a method for producing such nano-cannulas that can be implemented simply and with inexpensive means.
  • the invention achieves the stated object in comparison to the cited prior art on the basis of another basic idea.
  • the principle of the macro cannula as it is known from medical applications is applied in the nano dimension simulated.
  • two different individual parts namely (at least) a nano-hollow needle and a nano-adapter sealingly surrounding the hollow needle (s), are combined to form the nano-cannula.
  • a nanotube with an outer diameter of less than 100 nm and an inner diameter of less than 80 nm is used as the hollow needle.
  • such a nanotube is firmly inserted into a carrier film over a defined length, namely the length of the holding section, the carrier film forming the adapter.
  • the length of the holding section results from how deep the nanotube is in the carrier film.
  • the thickness of the carrier film is chosen to be less than about 100 micrometers, in particular less than 50 micrometers.
  • the nanotube protrudes from the carrier film (adapter). The part protruding from the carrier film thus defines a section “effective” for penetration into a microstructure, at the end of which the tip is located.
  • the length of the nano-tubes will be adapted to the thickness of the carrier film (or vice versa) and can be up to 1 mm.
  • nano-cannulas With the nano-cannulas according to the invention, it is possible to withdraw or inject liquid or gas in minimal quantities from an object, for example an individual cell or a collection of cells, such as those found in tissue, for example. Because of their small size and mass, however, direct handling of the nano cannulas is not possible. Therefore, it is advantageous to maneuver them with a microscopic positioning system as is commercially available. These positioning systems are known for the handling of micro pipettes and, as will be described below, can be modified for use with nano-cannulas. With these systems, nano-cannulas can then also be attached to moving target objects such as cells, proteins or DNA. This enables an accurate and targeted delivery and / or extraction of substances.
  • an object for example an individual cell or a collection of cells, such as those found in tissue, for example. Because of their small size and mass, however, direct handling of the nano cannulas is not possible. Therefore, it is advantageous to maneuver them with a microscopic positioning system as is commercially
  • the invention ultimately relates to a component of an injection device which has a single hollow nanoneedle or an entire arrangement of hollow nanoneedles, the nanoneedles being formed in particular by carbon nanotubes.
  • the device also has a holder designed as an adapter, which holds the one nanotube or the plurality of nanotubes arranged approximately in parallel.
  • the device according to the invention is particularly suitable for the construction of nano-pipettes, nano-syringes or nano-drills, with which cells, membranes, proteins or the like react extremely sensitively to mechanical damage and to the volume of the injectate Structures that can be applied.
  • the concept according to the invention has a number of advantages.
  • One major advantage is that it is now possible to manufacture large numbers of nano-cannulas with little technical effort.
  • the cannulas can be adapted to the intended use by appropriate choice of materials and by adjusting the dimensions of the individual parts.
  • the invention succeeds in developing a nanodimensional device which does not damage the target object when the cannula penetrates and which enables the injection of both small and large molecules, including nanoparticles and proteins. This device is of great diagnostic and therapeutic interest in biological and medical research and offers the possibility of manipulation on the smallest scale.
  • nanotubes made from carbon have improved tensile strength and bending elasticity, which is higher than is known from conventional carbon fibers. Such are also nanotubes even more resistant to oxidation than all other carbon modifications and can therefore be used at higher temperatures.
  • the nanotube In order to be able to guarantee secure continuity with high stability, it is advantageous if the nanotube completely penetrates the carrier film.
  • the length of the holding section corresponds to the thickness of the carrier film.
  • training There are two types of training, which should be preferred depending on the area of application and which differ in the way they are manufactured.
  • the nanotube opens into the plane of the surface of the carrier film facing the instrument. In other words, the nanotube only protrudes from the film with the effective section.
  • the holding section extends from the base of the nanotube by the thickness of the carrier film up to the tip of the nanotube.
  • nano-cannula is particularly preferred for injection instruments, since with these nano-cannulas it is possible to completely empty the instrument because there are no dead spaces.
  • manufacturing requires an additional manufacturing step. In this form, the nanotube extends beyond the plane of the surface of the carrier film facing the instrument.
  • the tools equipped with the nano-cannula according to the invention can be used several times. The possibility of easy cleaning of the cannula must be provided for this.
  • the nano-cannulas are disposable items that are discarded after use.
  • Chip technology is an advantageous area of application for the tools equipped with the nano-needles. There, the tools can be used in particular as manipulators. The invention is explained in more detail below with reference to FIGS. 1 to 4. Show it:
  • FIG. 1 different types of nano cannulas with an angular adapter
  • FIG. 2 shows a nano cannula with a round adapter
  • Figure 4 shows a method for producing a nano-cannula.
  • Figure 1 shows nano-cannulas that can be placed on a corresponding nano-syringe or a nano-pipette.
  • the cannulas consist essentially of two parts. So they have one or more hollow needles formed by carbon nanotubes 1.
  • the nanotubes 1 are sealed by an adapter, which in this case is formed by a carrier film 2 which is rectangular in this case. They have an outer diameter of approximately 50 nm and an inner diameter of approximately 30 nm.
  • the carrier film 2 has a thickness S of approximately 10 micrometers.
  • the dimensions shown in the figures are not to scale. This applies in particular to the edge length of the carrier film 2, which can ultimately have any dimensions up to the order of centimeters.
  • the carrier film 2 is a polymer film, the angular contour of which is cut after production. As can be seen from FIG. 3, the correspondingly contoured adapter 2 adapts to receiving means of the micro pipette of a positioning system.
  • the nanotubes 1 penetrate the carrier film 2 completely and protrude from the carrier film 2 on both sides to a certain extent. Since the nanotubes 1 are held over the entire layer thickness of the carrier film 2, the thickness S of the carrier film 2 also corresponds to the length of the holding section.
  • Each nanotube 1 has an effective section 3, which is closed by a tip 4.
  • the effective section 3 can be used to act on a target structure. It is possible to let the nanotubes into the carrier film 2 at an angle or to incline the effective section 3 relative to the surface of the carrier film 2.
  • FIG. 1 shows under a) a cannula with only one nanotube 1, which is suitable for the targeted application of a target structure.
  • the respective carrier film 2 is “peppered” with two or with a multiplicity of nanotubes 1 arranged in parallel, only four tubes being shown under c).
  • the distance A between the individual tubes corresponds approximately to the distance between individual eukaryotic ones Cells, in particular between 10 and 100 micrometers, of a cell cluster to be loaded with the instrument,
  • Figure 2 shows a nano-cannula with only one nanotube 1, which is inserted into a carrier film 2 cut into a circle.
  • the nanotubes can be made from any material, in particular from polymer, inorganic material, such as semiconductors or silica, from metal or from carbon.
  • the walls of the nanotubes can be made hydrophilic or hydrophobic depending on their use. They can even be provided with biological markers and / or nano objects.
  • FIG. 3 shows the end of a “macroscopic” pipette 5, which has a diameter of approximately 10 micrometers.
  • the pipette 5 is drawn from glass by a known method and is maneuvered by a positioning system (not shown).
  • a positioning system not shown.
  • the tip of the pipette 5 the an injection solution 6 is filled, there is a shoulder 7 which serves as a receptacle for a nano-cannula 8, the carrier film 9 of the nano-cannula 8 being cut into a corresponding diameter, in which case the nano-cannula 8 is in the Recording 7 glued in for sealing.
  • FIG. 4 shows the method for producing a nano-cannula in the three steps ac.
  • a template is produced, which is formed by a nano-tube 11 grown on a base 10.
  • a separating layer 12 made of soluble polymer is applied to this template and cured.
  • the separation layer 12 is dissolved in a last step, so that the nano-cannula 14 remains.
  • the soil is cut or peeled from the solidified polymer
  • This separation can be carried out in the manner of a microtome cut, it being advantageous to further harden the polymer 12 by freezing before making the cut.
  • the tube at the base area is cut through and thus opened on one side from below.

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nanotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Composite Materials (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Materials Engineering (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne une canule pour un instrument d'injection et/ou d'extraction, notamment pour une seringue ou une pipette. Cette canule comporte une aiguille creuse (1) entourée de manière hermétique par un adaptateur (2) qui coopère avec des dispositifs de réception correspondants de l'instrument à des fins de support. L'aiguille creuse est un nanotube (1) dont le diamètre externe est inférieur à 100 nm et le diamètre interne inférieur à 80 nm. Sur toute la longueur d'un segment support S, ce nanotube est fixé dans une feuille support (2) formant l'adaptateur, l'épaisseur de cette feuille étant inférieure à 100 micromètres, notamment inférieure à 50 micromètres. Ledit nanotube (1) se trouve en saillie sur une longueur (3) effective relativement à la feuille support (2), cet longueur étant enfermée par une pointe (4).
PCT/EP2005/004437 2004-05-25 2005-04-26 Nano-canule Ceased WO2005115623A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102004026087.7 2004-05-25
DE200410026087 DE102004026087A1 (de) 2004-05-25 2004-05-25 Nano-Kanüle

Publications (1)

Publication Number Publication Date
WO2005115623A1 true WO2005115623A1 (fr) 2005-12-08

Family

ID=34966154

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/004437 Ceased WO2005115623A1 (fr) 2004-05-25 2005-04-26 Nano-canule

Country Status (2)

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DE (1) DE102004026087A1 (fr)
WO (1) WO2005115623A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007080435A1 (fr) * 2006-01-09 2007-07-19 Michael Solomakakis Aiguille dite 'moustique' comprenant des nanotubes de carbone
RU2341299C2 (ru) * 2006-12-28 2008-12-20 Институт физики полупроводников Сибирского отделения Российской академии наук Полая наноигла в интегральном исполнении и способ ее изготовления

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102007038280B4 (de) * 2007-08-03 2010-11-25 Leibniz-Institut Für Festkörper- Und Werkstoffforschung Dresden E.V. Aktuator und Verfahren zu seiner Herstellung

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4979943A (en) * 1990-03-15 1990-12-25 Trenner Lewis E Single use hypodermic syringe
US5457041A (en) * 1994-03-25 1995-10-10 Science Applications International Corporation Needle array and method of introducing biological substances into living cells using the needle array
WO1998028406A1 (fr) * 1996-12-20 1998-07-02 Genesystems, Inc. Methode et dispositif pour micro-injection de macromolecules dans des cellules non adherentes
US6334856B1 (en) * 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
WO2002045771A2 (fr) * 2000-11-09 2002-06-13 Biovalve Technologies, Inc. Adaptateur pour micro-aiguilles
US20030015807A1 (en) * 2001-06-21 2003-01-23 Montemagno Carlo D. Nanosyringe array and method

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039250A1 (fr) * 1997-03-07 1998-09-11 William Marsh Rice University Fibres de carbone produites a partir de nanotubes en carbone a paroi simple
EP0992577B1 (fr) * 1998-06-05 2000-07-26 Lummel, Wolfgang Procédé de microinjection et nanopipettes pour l'introduction d'un produit d'injection, plus particulièrement un materiau génétique étranger dans des cellules procaryotes ou eucaryotes ou dans desc compartiments cellulaires de celles-ci (plastides, noyau cellulaire)
JP2003246700A (ja) * 2002-02-22 2003-09-02 Japan Science & Technology Corp シリコンナノニードルの製法
US20040063100A1 (en) * 2002-09-30 2004-04-01 Wang Chung Lin Nanoneedle chips and the production thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4979943A (en) * 1990-03-15 1990-12-25 Trenner Lewis E Single use hypodermic syringe
US5457041A (en) * 1994-03-25 1995-10-10 Science Applications International Corporation Needle array and method of introducing biological substances into living cells using the needle array
WO1998028406A1 (fr) * 1996-12-20 1998-07-02 Genesystems, Inc. Methode et dispositif pour micro-injection de macromolecules dans des cellules non adherentes
US6334856B1 (en) * 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
WO2002045771A2 (fr) * 2000-11-09 2002-06-13 Biovalve Technologies, Inc. Adaptateur pour micro-aiguilles
US20030015807A1 (en) * 2001-06-21 2003-01-23 Montemagno Carlo D. Nanosyringe array and method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
8TH WORKSHOP ON MICROMACHINING, MICROMECHANICS AND MICROSYSTEMS 31 AUG.-2 SEPT. 1997 SOUTHAMPTON, UK, vol. 8, no. 2, June 1998 (1998-06-01), Journal of Micromechanics and Microengineering IOP Publishing UK, pages 144 - 147, XP002342209, ISSN: 0960-1317 *
PRINZ A V ET AL: "Semiconductor micro- and nanoneedles for microinjections and ink-jet printing", MICROELECTRONIC ENGINEERING, ELSEVIER PUBLISHERS BV., AMSTERDAM, NL, vol. 67-68, June 2003 (2003-06-01), pages 782 - 788, XP004428950, ISSN: 0167-9317 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007080435A1 (fr) * 2006-01-09 2007-07-19 Michael Solomakakis Aiguille dite 'moustique' comprenant des nanotubes de carbone
RU2341299C2 (ru) * 2006-12-28 2008-12-20 Институт физики полупроводников Сибирского отделения Российской академии наук Полая наноигла в интегральном исполнении и способ ее изготовления

Also Published As

Publication number Publication date
DE102004026087A1 (de) 2005-12-15

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