WO2001048181A2 - Vorrichtung zum transfer von molekülen in zellen - Google Patents
Vorrichtung zum transfer von molekülen in zellen Download PDFInfo
- Publication number
- WO2001048181A2 WO2001048181A2 PCT/DE2000/004631 DE0004631W WO0148181A2 WO 2001048181 A2 WO2001048181 A2 WO 2001048181A2 DE 0004631 W DE0004631 W DE 0004631W WO 0148181 A2 WO0148181 A2 WO 0148181A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- source
- molecules
- acoustic pulses
- medium
- cells
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
Definitions
- the invention relates to a device according to the preamble of claim 1
- Sonotrodes must first be brought into resonance in order to generate vibrations which have such a high amplitude that exceeds the cavitation threshold. In a disadvantageous manner, individual pulses are therefore not possible. This also has the disadvantage that too high a "dose" of cavitation events act on the cells and the cells are thereby destroyed.
- the considerations that led to the creation of the invention adopted the knowledge that a hollow cylindrical device into which a multitude of in-phase sound pulses are introduced radially from the outside produces a reproducible zone of transient cavitation events in the area around the axis of rotation of the hollow cylinder.
- the considerations that led to the development of the invention assumed that it is irrelevant for the transfer of the molecules into the target cells, how large is the total amount of the medium in which the molecules and target cells to be transferred are located, if any parts from the total amount successively reach the effective range of the acoustic pulses and the target cells contained therein are thus exposed to treatment.
- This relative movement can now take place by moving the source relative to a fixed liquid container or by moving the liquid container relative to a fixed source.
- the medium with the target cells and the molecules to be transferred can also move through a line system while it is under the influence of the focused acoustic pulses.
- the parameters must be matched to one another in such a way that the target cells are exposed to at least the predetermined number of pulses as they move through the line system.
- FIG. 1 shows a possible embodiment of the invention.
- Acoustic pulses are generated by means of an essentially hollow cylindrical source 1, through which a tubular line 2 is guided.
- the medium is located in this line 2.
- it is a liquid F that has a viscosity that allows it to flow through line 2.
- the source 1 is designed in such a way that it focuses the acoustic pulses in its interior and thus in the area in which the line 2 runs.
- the focus here is essentially axial.
- the area of the focus is the so-called effective area of the acoustic pulses, which is why it is called the focus area in the following.
- the source 1 is designed to be rotationally symmetrical cylindrical.
- the wall of line 2 is permeable to acoustic pulses at least in the area of the focus.
- the principle of excitation for the acoustic pulses is to use a large number of piezo elements, all of which are concentrically directed in the direction of the axis of rotation and are excited simultaneously, in phase. In this way it is possible to create an elongated focus area.
- cylindrical source instead of a plurality of piezo elements concentrically aligned with the axis of rotation by means of a plurality of piezo rings lying next to one another, the center of which lie on the axis of rotation. It is also possible to use magnetostrictive actuators to generate the acoustic pulses
- a further embodiment of the invention provides for the source 1 to be designed as a hollow body with a semicircular cross section as a more channel-shaped body.
- the source 1 there is a focus area that extends approximately over the length of the source.
- the line in which the liquid F is located runs through this elongated focus area. This has the advantage that the source can be coupled to an existing line and the line does not first have to be laid through the hollow cylindrical source 1.
- the source can advantageously be coupled to an existing line.
- the design of a source 1 according to FIG. 2 with a semicircular cross section offers the advantage that the source can easily be attached to a line from the side without the line having to be laid through the interior of the source.
- a coil can also be used for the excitation, which acts on a membrane located within the coil and thus generates an inwardly directed acoustic pulse.
- Acoustic pulses are emitted by the source 1 onto the liquid F and briefly create conditions there (pressure or negative pressure with sufficient intensity, cavitation) in order to bring about a transfer of the molecules into the target cells.
- the molecules can be transferred into the cells within wide pressure or negative pressure ranges.
- the pressure ranges are between 10 Mpa and 150 Mpa.
- the vacuum ranges from -5 Mpa to -50 Mpa.
- the intensity is between 0.5 mJ / mm2 and 5.0 mJ / mm2.
- the flow rate Vf of the liquid F can be changed by a pump, which is not shown for reasons of clarity.
- the source 1 is excited by a unit 3 in pulse form.
- the target cells and the molecules to be transferred are exposed to a predetermined number of acoustic pulses of a predetermined intensity.
- the liquid F flow through the line 2 in a pulsed or clocked manner.
- the liquid F is always conveyed in such a way that the area which was just in front of the source 1 in the line is conveyed so far that it then comes to a standstill at the end of the source 1. While the liquid area within source 1 is in the focus of the acoustic pulses, a predetermined number becomes emitted by acoustic pulses that stimulate the transfer of molecules into the target cells.
- the acoustic pulses that act on the liquid or generally formulated on the medium can consist of ultrasound pulses or one or more successive shock waves.
- the intensity (unit of measurement mJ / mm2) of the ultrasound impulses or shock waves also influences both the number of intracellularly transferred molecules and the damage to the cells. With increasing intensity, there is an increase in both the number of intracellularly transferred molecules and the damaged cell.
- the container can be of any shape here, but it is crucial that the movement of the container takes place in such a way that the entire volume of the container has successively reached the effective range of the acoustic pulses.
- All movements of the medium relative to the source of acoustic pulses can be continuous or clocked.
- the molecules to be transferred are fed to the medium in which the target cells are located only directly before the focus area.
- the source shown in FIG. 3 consists of an inner ring 3, which can accommodate the line (not shown here) or a sample tube in its inner free space 7.
- Piezo elements 4 are arranged distributed around the outer circumference of the inner ring 3. For reasons of clarity, only some of these piezo elements 4 are shown in this illustration.
- the piezo elements 4 are held on their side facing away from the inner ring 3 by a further ring 6.
- the outer ring 6 is designed as a clamping ring. Its inside diameter can be changed using a clamping screw 2. This also changes the gap 1.
- the piezo elements 4 can be firmly clamped between the inner ring 3 and the outer clamping ring 6. This ensures good sound transmission between the piezo elements 4 and the rings 4 and 6.
- FIG. 4 shows a further version of the device according to the invention.
- the piezo elements 4 are arranged around the inner ring 3 in the manner known from FIG. 3.
- An intermediate ring 8 rests on its side facing away from the inner ring 3.
- Piezo elements 7 are in turn arranged on this intermediate ring 8. These piezo elements 7 are followed by the clamping ring 6 already known from FIG. 3.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00990583A EP1244770A2 (de) | 1999-12-23 | 2000-12-23 | Vorrichtung zum transfer von molekülen in zellen |
CA002397271A CA2397271A1 (en) | 1999-12-23 | 2000-12-23 | Method for transferring molecules in cells |
JP2001548694A JP2003533974A (ja) | 1999-12-23 | 2000-12-23 | 細胞内に分子を導入する装置 |
US10/177,823 US20030017578A1 (en) | 1999-12-23 | 2002-06-21 | Apparatus for transferring molecules into cells |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19962904.8 | 1999-12-23 | ||
DE1999162904 DE19962904A1 (de) | 1999-12-23 | 1999-12-23 | Verfahren zum Transfer von Molekülen in Zellen und Vorrichtung zur Durchführung des Verfahrens |
DE10063942.9 | 2000-12-20 | ||
DE10063942 | 2000-12-20 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/177,823 Continuation US20030017578A1 (en) | 1999-12-23 | 2002-06-21 | Apparatus for transferring molecules into cells |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001048181A2 true WO2001048181A2 (de) | 2001-07-05 |
WO2001048181A3 WO2001048181A3 (de) | 2002-04-18 |
Family
ID=26008022
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE2000/004631 WO2001048181A2 (de) | 1999-12-23 | 2000-12-23 | Vorrichtung zum transfer von molekülen in zellen |
Country Status (5)
Country | Link |
---|---|
US (1) | US20030017578A1 (de) |
EP (1) | EP1244770A2 (de) |
JP (1) | JP2003533974A (de) |
CA (1) | CA2397271A1 (de) |
WO (1) | WO2001048181A2 (de) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002066597A1 (de) * | 2001-02-19 | 2002-08-29 | Dornier Medtech Systems Gmbh | Verfahren und vorrichtung zur ultraschallimpfung von biologischem zellmaterial |
EP1365016A2 (de) * | 2002-05-24 | 2003-11-26 | Dornier MedTech Systems GmbH | Verfahren und Einrichtung zum Transferieren medizinisch wirksamer Stoffe in Zellen |
WO2003101609A1 (en) * | 2002-05-30 | 2003-12-11 | Nano-Size Ltd. | Ultrasonic reactor and process for ultrasonic treatment of materials |
EP1702065A1 (de) * | 2003-12-01 | 2006-09-20 | Richard E. Walters | Kammer mit nicht gleichförmigem elektrischem feld zur zellfusion |
WO2011113938A1 (en) * | 2010-03-19 | 2011-09-22 | Commissariat à l'énergie atomique et aux énergies alternatives | Agitator of a liquid sample |
US9060915B2 (en) | 2004-12-15 | 2015-06-23 | Dornier MedTech Systems, GmbH | Methods for improving cell therapy and tissue regeneration in patients with cardiovascular diseases by means of shockwaves |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10211886B4 (de) * | 2002-03-18 | 2004-07-15 | Dornier Medtech Gmbh | Verfahren und Einrichtung zum Erzeugen bipolarer akustischer Impulse |
US11046596B2 (en) | 2012-10-25 | 2021-06-29 | Hydrus Technology Pty. Ltd. | Electrochemical liquid treatment apparatus |
US11046595B2 (en) | 2014-05-23 | 2021-06-29 | Hydrus Technology Pty. Ltd. | Electrochemical treatment methods |
WO2015176137A1 (en) | 2014-05-23 | 2015-11-26 | Hydrus Technology Pty. Ltd. | Electrochemical treatment methods |
JP6367493B2 (ja) * | 2015-01-07 | 2018-08-01 | インディー.インコーポレイテッド | 機械的及び流体力学的マイクロ流体形質移入の方法ならびにそのための装置 |
KR102232757B1 (ko) * | 2018-11-22 | 2021-03-26 | (주)엑솔런스바이오테크놀로지 | 체외충격파를 이용한 표적물질 전달 장치 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989002464A1 (en) * | 1987-09-07 | 1989-03-23 | Amersham International Plc | Modifying living cells |
DE3821354A1 (de) * | 1987-07-10 | 1989-07-06 | Berlin Kosmetik Veb | Verfahren und vorrichtung zur herstellung bioaktiver suspensionen |
EP0326701A2 (de) * | 1988-02-04 | 1989-08-09 | Dornier Medizintechnik Gmbh | Piezoelektrische Stosswellenquelle |
WO1999058637A2 (de) * | 1998-05-07 | 1999-11-18 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Vorrichtung und verfahren zur gezielten beaufschlagung einer biologischen probe mit schallwellen |
WO2000008195A1 (de) * | 1998-07-31 | 2000-02-17 | Dornier Medtech Holding International Gmbh | Verfahren und vorrichtung zum transfer von oligonukleotiden in die zelle |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2578505A (en) * | 1948-03-02 | 1951-12-11 | Sperry Prod Inc | Supersonic agitation |
US3406302A (en) * | 1966-03-15 | 1968-10-15 | Westinghouse Electric Corp | Cylindrical magnetostrictive electromechanical transducer |
DE2346649A1 (de) * | 1973-09-17 | 1975-03-27 | Ngk Spark Plug Co | Ultraschallgeber |
US4369100A (en) * | 1977-09-27 | 1983-01-18 | Sawyer Harold T | Method for enhancing chemical reactions |
US5395592A (en) * | 1993-10-04 | 1995-03-07 | Bolleman; Brent | Acoustic liquid processing device |
CA2238951A1 (fr) * | 1998-05-26 | 1999-11-26 | Les Technologies Sonomax Inc. | Reacteur a cavitation acoustique pour le traitement des materiaux |
-
2000
- 2000-12-23 JP JP2001548694A patent/JP2003533974A/ja active Pending
- 2000-12-23 EP EP00990583A patent/EP1244770A2/de not_active Withdrawn
- 2000-12-23 WO PCT/DE2000/004631 patent/WO2001048181A2/de not_active Application Discontinuation
- 2000-12-23 CA CA002397271A patent/CA2397271A1/en not_active Abandoned
-
2002
- 2002-06-21 US US10/177,823 patent/US20030017578A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3821354A1 (de) * | 1987-07-10 | 1989-07-06 | Berlin Kosmetik Veb | Verfahren und vorrichtung zur herstellung bioaktiver suspensionen |
WO1989002464A1 (en) * | 1987-09-07 | 1989-03-23 | Amersham International Plc | Modifying living cells |
EP0326701A2 (de) * | 1988-02-04 | 1989-08-09 | Dornier Medizintechnik Gmbh | Piezoelektrische Stosswellenquelle |
WO1999058637A2 (de) * | 1998-05-07 | 1999-11-18 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Vorrichtung und verfahren zur gezielten beaufschlagung einer biologischen probe mit schallwellen |
WO2000008195A1 (de) * | 1998-07-31 | 2000-02-17 | Dornier Medtech Holding International Gmbh | Verfahren und vorrichtung zum transfer von oligonukleotiden in die zelle |
Non-Patent Citations (2)
Title |
---|
HUBER PETER E ET AL: "A comparison of shock wave and sinusoidal-focused ultrasound-induced localized transfection of HeLa cells." ULTRASOUND IN MEDICINE AND BIOLOGY, Bd. 25, Nr. 9, November 1999 (1999-11), Seiten 1451-1457, XP001005203 ISSN: 0301-5629 * |
MILLER DOUGLAS L ET AL: "Sonoporation of cultured cells in the rotating tube exposure system." ULTRASOUND IN MEDICINE AND BIOLOGY, Bd. 25, Nr. 1, Januar 1999 (1999-01), Seiten 143-149, XP001005257 ISSN: 0301-5629 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002066597A1 (de) * | 2001-02-19 | 2002-08-29 | Dornier Medtech Systems Gmbh | Verfahren und vorrichtung zur ultraschallimpfung von biologischem zellmaterial |
EP1365016A2 (de) * | 2002-05-24 | 2003-11-26 | Dornier MedTech Systems GmbH | Verfahren und Einrichtung zum Transferieren medizinisch wirksamer Stoffe in Zellen |
DE10223196A1 (de) * | 2002-05-24 | 2003-12-11 | Dornier Medtech Systems Gmbh | Verfahren und Einrichtung zum Transferieren medizinisch wirksamer Stoffe in Zellen |
EP1365016A3 (de) * | 2002-05-24 | 2004-01-21 | Dornier MedTech Systems GmbH | Verfahren und Einrichtung zum Transferieren medizinisch wirksamer Stoffe in Zellen |
DE10223196B4 (de) * | 2002-05-24 | 2004-05-13 | Dornier Medtech Systems Gmbh | Verfahren und Einrichtung zum Transferieren von Molekülen in Zellen |
US7267659B2 (en) | 2002-05-24 | 2007-09-11 | Dornier Medtech Systems Gmbh | Method and apparatus for transferring medically effective substances into cells |
US7504075B2 (en) | 2002-05-30 | 2009-03-17 | Nano-Size Ltd. | Ultrasonic reactor and process for ultrasonic treatment of materials |
WO2003101609A1 (en) * | 2002-05-30 | 2003-12-11 | Nano-Size Ltd. | Ultrasonic reactor and process for ultrasonic treatment of materials |
EP1702065A1 (de) * | 2003-12-01 | 2006-09-20 | Richard E. Walters | Kammer mit nicht gleichförmigem elektrischem feld zur zellfusion |
EP1702065A4 (de) * | 2003-12-01 | 2009-04-29 | Richard E Walters | Kammer mit nicht gleichförmigem elektrischem feld zur zellfusion |
US9060915B2 (en) | 2004-12-15 | 2015-06-23 | Dornier MedTech Systems, GmbH | Methods for improving cell therapy and tissue regeneration in patients with cardiovascular diseases by means of shockwaves |
WO2011113938A1 (en) * | 2010-03-19 | 2011-09-22 | Commissariat à l'énergie atomique et aux énergies alternatives | Agitator of a liquid sample |
FR2957532A1 (fr) * | 2010-03-19 | 2011-09-23 | Commissariat Energie Atomique | Agitateur d'un echantillon liquide |
Also Published As
Publication number | Publication date |
---|---|
WO2001048181A3 (de) | 2002-04-18 |
JP2003533974A (ja) | 2003-11-18 |
CA2397271A1 (en) | 2001-07-05 |
US20030017578A1 (en) | 2003-01-23 |
EP1244770A2 (de) | 2002-10-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1187563B1 (de) | Medizinisches instrument zur behandlung von biologischem gewebe sowie verfahren zum übertragen von druckwellen | |
WO2001048181A2 (de) | Vorrichtung zum transfer von molekülen in zellen | |
WO1987003797A1 (en) | Installation for the acoustical and mechanical coupling of pressure waves, especially focussed shock waves on the body of living beings | |
DE202007012531U1 (de) | Massagegerät | |
EP0189756A1 (de) | Einrichtung zur Erzeugung zeitlich versetzter Stosswellen | |
DE2415481C3 (de) | Ultraschallgenerator | |
EP2529678B1 (de) | Druckwellengerät zur Behandlung des menschlichen oder tierischen Körpers | |
EP0254104A1 (de) | Stosswellengenerator zur Erzeugung eines akustischen Stosswellenimpulses | |
DE102009018988A1 (de) | Oberflächenverfestigung dünnwandiger Bauteile | |
DE10394286T5 (de) | Vorrichtung für verbesserte Schockwellen-Nierenzertrümmerung (SWL) unter Verwendung eines piezoelektrischen Ringanordnungs- (PEAA) Schockwellengenerators in Kombination mit einer primären Schockwellenquelle | |
DE2801378C2 (de) | Rohrleitungsmolch | |
DE102007013288A1 (de) | Vorrichtung zur Behandlung biologischer Körpersubstanzen mit mechanischen Druckwellen | |
EP0364662A1 (de) | Gummilager | |
DE19962904A1 (de) | Verfahren zum Transfer von Molekülen in Zellen und Vorrichtung zur Durchführung des Verfahrens | |
DE10242072A1 (de) | Piezoelektrischer Wandler | |
DE4323212C2 (de) | Vorrichtung zum Behandeln strömender Medien mit Ultraschall | |
DE4102090A1 (de) | Medizinisches ultraschall-abtraginstrument | |
DE102005022034A1 (de) | Medizinisches Instrument zur Behandlung von biologischem Gewebe | |
CH425665A (de) | Ultraschallzerstäuber | |
DE10013451B4 (de) | Vorrichtung zur Erzeugung monodisperser Tropfen | |
AT403219B (de) | Vorrichtung zum ansteuern eines hydrostatischen antriebes | |
DE2923711A1 (de) | Ultraschallsonde | |
EP1951449B1 (de) | Ultraschall-reinigungssystem für hohlkörper | |
EP4039202B1 (de) | Vorrichtung zur erzeugung von stosswellen, insbesondere zur erzeugung eines komprimierten stosswellenwirkfeldes | |
WO1988003782A1 (en) | Process and device for eliminating the traumatic effects of the fragmentation of kidney stones |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): CA CN JP RU SG US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): CA CN JP RU SG US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2397271 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000990583 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2001 548694 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10177823 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 2000990583 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000990583 Country of ref document: EP |