WO2012157007A1 - Dispositif de génération de microgravité - Google Patents

Dispositif de génération de microgravité Download PDF

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Publication number
WO2012157007A1
WO2012157007A1 PCT/IT2012/000090 IT2012000090W WO2012157007A1 WO 2012157007 A1 WO2012157007 A1 WO 2012157007A1 IT 2012000090 W IT2012000090 W IT 2012000090W WO 2012157007 A1 WO2012157007 A1 WO 2012157007A1
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WO
WIPO (PCT)
Prior art keywords
flow chamber
micro
generating device
base
fluid
Prior art date
Application number
PCT/IT2012/000090
Other languages
English (en)
Other versions
WO2012157007A8 (fr
Inventor
Giuseppe FALVO D'URSO LABATE
Diana MASSAI
Francesco PANNELLA
Diego Gallo
Maria MONTEVECCHI FRANCO
Umberto Morbiducci
Giulia CERINO ABDIN
Original Assignee
Politecnico Di Torino
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 Politecnico Di Torino filed Critical Politecnico Di Torino
Publication of WO2012157007A1 publication Critical patent/WO2012157007A1/fr
Publication of WO2012157007A8 publication Critical patent/WO2012157007A8/fr

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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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • 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
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/18—Flow directing inserts
    • 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 present invention refers to a micro- gravity generating device.
  • Devices are known in the art that are able to generate a micro-gravity condition for a solvent contained inside a flow chamber: examples of such devices are disclosed in EP2265708, RU2355751, US20110027880, WO20080733.48, US2010120136.. Such devices belonging to the prior art obtain the micro-gravity conditions by means of rotary components handled by actuators. The presence of such rotary components however has some inconveniences .
  • Document RU-Cl-2 355 752 discloses a device according to the preamble of Claim 1.
  • object of the present invention is solving the above prior art problems by providing a device able to generate micro-gravity even if there are no rotary components.
  • Another object of the present invention is providing a passive micro-gravity generating device able to exploit a fluid-dynamics inside a flow chamber with an optimised geometry to . generate micro-gravity at low costs.
  • Figure 1 shows a side sectional view of a preferred embodiment of the micro-gravity generating device according to the present invention in a first operating position thereof;
  • Figure 2 shows a side sectional view of a preferred . ⁇ embodiment of the micro-gravity generating device according to the present invention in a second operating position thereof;
  • Figure 3 shows an axial-symmetrical discrete 2D computational simulation of the micro-gravity generating device according to the present invention;
  • Figure 4 shows a colour-metric map of the fluid speed values inside the micro-gravity generating device according to the present invention
  • Figure 5 shows a colour-metric map of the fluid vortex values inside the micro-gravity generating device according to the present invention.
  • Figure 6 shows a colour-metric map of the fluid deformation speed values inside the micro- gravity generating device according to the present invention.
  • the device according to the present invention is adapted to generate micro- gravity conditions in systems in which it is necessary preferably to perform perfusion or fluid re-circulation such as, for example, bio-reactors.
  • the device according to the present invention comprises at least one flow chamber characterised by an internal geometry, designed with the help of information deriving from in silico studies, adapted to produce the detachment of the fluid vein from the wall of such chamber within a certain speed range of the inlet fluid and to generate vortexes able to keep particles with different sizes in suspension, ensuring a laminar speed in every point of the chamber itself, under certain operating conditions, avoiding the use of rotary devices.
  • the micro- gravity generating device 1 comprises at least one flow chamber 3 to which at least one supplying circuit 5, preferably of the hydraulic type, is connected, adapted to supply the interior of such flow chamber 3 with at least one fluid F, such flow chamber 3 being such as to delimit, at least internally, a volume defined by at least one lower vase 4 composed of at least one base 7 ad at least lateral slanted walls 9, and at least one upper cover 11, such base 7 being connected on its perimeter to such lateral slanted walls 9 by interposing at least one curvilinear junction profile 13.
  • the flow chamber 3 is axial-symmetrical with respect to an axis of symmetry S ⁇ S.
  • the supplying circuit 5 supplies fluid F inside the flow chamber 3 through at least one supplying opening 15 placed through the base 7 in a coaxial position with respect to such axis of symmetry S-S.
  • at least one check valve is interposed, arranged next to such supplying opening 15. The check valve results open (as shown, for example, in Figure 2) only under fluid F re-circulation conditions, being automatically closed (as shown, for example, in Figure 1) as soon as the flow is stopped, thereby preventing the contents of chamber 3 from out- flowing when the device 1 is inactive.
  • such check valve comprises at least one plunger 17 inside the internal volume of the' lower vase 4 and adapted to be moved vertically and coaxially with respect to the axis of symmetry S-S in order to open or close the supplying opening 15 (and therefore allow the passage of fluid F inside the -flow chamber 3, or not),
  • plunger IT being preferably shaped as a right circular frustum of cone.
  • the lateral slanted walls 9, the base 7 and the junction profile 13 are mutually integral and made of the same material.
  • the device 1 according to the present invention can be equipped with a suitable ⁇ supporting structure 19 that guarantees placement and necessary stability for the flow chamber 3.
  • the internal volume of the flow chamber 3 can be divided by at least one filtering layer 21 interposed between the lower vase 4 and the cover 11, such filtering layer being adapted to block elements being present inside fluid F from occasionally flow out.
  • the cover 11 can further be equipped with at least one discharge duct 12 for fluid F.
  • the geometry of the internal volume of the flow chamber 3 is devised in order to favour the occurrence of stationary vortexes V in fluid F (solute - solvent solution) supplied by the supplying circuit 5 in order to create a micro- gravity and mixing condition for the solute without the help of rotary components.
  • fluid F solvent - solvent solution
  • - A/B is included between 0.4 and 0.7;
  • - A/C is included between 1 and 1.5;
  • - B/C is included between 2 and 3;
  • - R/B is included between 0.2 and 0.5;
  • - R/A is included between 0.4 and 0.8;
  • - - a is included between 40° and 60°;
  • - D/C is included between 0.05 and 0.1;
  • - C/F is included between 0.6 and 1.3.
  • the inlet speed of fluid F inside the flow chamber 3 through the supplying opening 15 is included between 0.05 m/s and 0.15 m/s.
  • fluid F is pumped inside the flow chamber 3, through the supplying duct 5 and the related supplying opening 15, where, following the vein detachment induced (and controlled) by the slant of the side walls 9, stationary vortexes V and hydrodynamic forces are formed, that are able to compensate the force of gravity and to avoid the solute sedimentation on the bottom of the chamber 3.
  • the Applicant has performed CFD simulations.
  • aim of the CFD simulations was to establish whether the internal geometry of the flow chamber 3 is able to ensure a homogeneous distribution of the cell- hydrogel aggregates, fluctuating inside the chamber 3 itself, in order to obtain the suspension of the aggregates,, avoiding their sedimentation on the chamber bottom, their- packing and their collision against the filter.
  • a device 1 according to the present invention has therefore been made and experimentally tested, with the following characteristic dimensions:
  • Figure 2 shows the discrete axial-symmetrical 2D computational simulation of the device. 1 according to the present invention
  • Figures 4 to 6 propose colour-metric maps obtained during the simulation tests of the above-described device 1 according to the present invention.
  • the device 1 has an axial symmetry, for the computational simulation, it has been possible to adopt an axial- symmetrical 2d domain.
  • the geometry has been made discrete with 206275 triangular cells (through the Gambit software supplied by ANSYS Inc., and making the simulation of Figure 3) .
  • the fluid vein detachment brings about the formation of a great vortex structure that is able to compensate, with the hydrodynamic forces that are generated in the bio-reactor, the force of gravity acting on the hydrogels, avoiding their sedimentation.
  • Such vein detachment that brings about the vortex formation, is guaranteed through the appropriate sizing of the chamber 3, in particular by the slanting of the side wall and the curvature of the junction profile with the base of the lower vase: at steady state, the profile curvature and the chamber wall slanting allow the inlet fluid, having a fluid-dynamic structure shaped as a jet, to rise along the side wall till the fluid vein detachment from the wall with the following formation of the above vortex due to an inertia effect.
  • the adopted geometric solution and the speed value imposed as inlet to the fluid thereby allow the device 1 according to the present invention to obtain a micro-gravity condition, with non-critical shearing effort values for the cells being present inside the chamber.
  • the device 1 according to the present invention further allows obtaining the following advantages:
  • the device 1 is devised in such a way as to ensure a laminar fluid-dynamic state in any point of the chamber 3, ensuring thereby a tolerable level of shearing efforts from living cells, in the application where this is required;
  • the device 1 has easily scalable dimensions, possibly allowing to strongly reduce the overall sizes also due to the absence . of rotary actuators, this allowing to use the device without problems, for example, like bio-reactor for tissue engineering, making it able to be easily inserted inside commercial incubators like those commonly used for cellular growths;
  • the device 1 operating in series with the other devices , does not require other energgy sources to obtain the micro-gravity condition for the solute .

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Mechanical Engineering (AREA)
  • Clinical Laboratory Science (AREA)
  • Cell Biology (AREA)
  • Permanent Magnet Type Synchronous Machine (AREA)
  • Saccharide Compounds (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)
  • Micromachines (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un dispositif de génération de microgravité (1) comprenant au moins une chambre d'écoulement (3) à laquelle est relié au moins un circuit d'alimentation (5),conçu pour alimenter l'intérieur d'une chambre d'écoulement (3) de ce type en au moins un fluide (F), la chambre d'écoulement (3) délimitant au moins le volume interne défini par au moins un vase inférieur (4) comprenant au moins un fond (7), au moins des parois latérales inclinées (9) et au moins un couvercle supérieur (11), de telle sorte que le fond (7) est relié au niveau de son périmètre aux parois latérales inclinées (9), par interposition d'au moins un profilé de liaison (13).
PCT/IT2012/000090 2011-05-16 2012-03-26 Dispositif de génération de microgravité WO2012157007A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITTO2011A000432 2011-05-16
IT000432A ITTO20110432A1 (it) 2011-05-16 2011-05-16 Dispositivo generatore di microgravità.

Publications (2)

Publication Number Publication Date
WO2012157007A1 true WO2012157007A1 (fr) 2012-11-22
WO2012157007A8 WO2012157007A8 (fr) 2013-03-14

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PCT/IT2012/000090 WO2012157007A1 (fr) 2011-05-16 2012-03-26 Dispositif de génération de microgravité

Country Status (2)

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IT (1) ITTO20110432A1 (fr)
WO (1) WO2012157007A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201800010212A1 (it) 2018-11-09 2020-05-09 Cellex S R L Dispositivo di coltura cellulare in sospensione
WO2024189527A1 (fr) * 2023-03-15 2024-09-19 Cellex S.R.L. Dispositif de culture en suspension de cellules pourvu d'un déviateur de flux

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5248613A (en) * 1991-07-08 1993-09-28 Roubicek Rudolf V Nonhomogeneous centrifugal film bioreactor
WO2007039726A1 (fr) * 2005-10-01 2007-04-12 The University Of Strathclyde Réacteur comprenant un espace de réaction de forme annulaire
WO2008073348A2 (fr) 2006-12-08 2008-06-19 Marshall University Research Corporation Systèmes de bioréacteurs utilisant des conditions de microgravité destinés à produire des composés bioactifs et des macromolécules biologiques
RU2355752C1 (ru) 2007-12-19 2009-05-20 Федеральное государственное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФГУН ГНЦ ВБ "Вектор" Роспотребнадзора) Аппарат для культивирования клеток тканей или микроорганизмов в условиях невесомости
RU2355751C1 (ru) 2008-04-07 2009-05-20 Андрей Петрович Репков Вихревой реактор для проведения биотехнологических процессов в условиях микрогравитации
US20100120136A1 (en) 2005-12-30 2010-05-13 Drug-Mode Aps Bioreactor for cell and tissue culture
EP2265708A2 (fr) 2008-03-18 2010-12-29 Marshall University Research Corporation Procédés de production de cellules souches et thérapie
US20110027880A1 (en) 2008-01-14 2011-02-03 University Of Brighton Cell culture system for pancreatic islands

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5248613A (en) * 1991-07-08 1993-09-28 Roubicek Rudolf V Nonhomogeneous centrifugal film bioreactor
WO2007039726A1 (fr) * 2005-10-01 2007-04-12 The University Of Strathclyde Réacteur comprenant un espace de réaction de forme annulaire
US20100120136A1 (en) 2005-12-30 2010-05-13 Drug-Mode Aps Bioreactor for cell and tissue culture
WO2008073348A2 (fr) 2006-12-08 2008-06-19 Marshall University Research Corporation Systèmes de bioréacteurs utilisant des conditions de microgravité destinés à produire des composés bioactifs et des macromolécules biologiques
RU2355752C1 (ru) 2007-12-19 2009-05-20 Федеральное государственное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФГУН ГНЦ ВБ "Вектор" Роспотребнадзора) Аппарат для культивирования клеток тканей или микроорганизмов в условиях невесомости
US20110027880A1 (en) 2008-01-14 2011-02-03 University Of Brighton Cell culture system for pancreatic islands
EP2265708A2 (fr) 2008-03-18 2010-12-29 Marshall University Research Corporation Procédés de production de cellules souches et thérapie
RU2355751C1 (ru) 2008-04-07 2009-05-20 Андрей Петрович Репков Вихревой реактор для проведения биотехнологических процессов в условиях микрогравитации

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIN ET AL.: "The influence of inclination of a solid surface on contact angles due to the effect of line tension", COLLOIDS AND SURFACTANTS A:PHYSICOCHEMICAL AND ENGINNERING ASPECTS, vol. 87, 1994, pages 93 - 100, XP002666099 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201800010212A1 (it) 2018-11-09 2020-05-09 Cellex S R L Dispositivo di coltura cellulare in sospensione
WO2020095143A1 (fr) * 2018-11-09 2020-05-14 Cellex S.R.L. Dispositif pour une culture de suspension cellulaire
US12084647B2 (en) 2018-11-09 2024-09-10 Cellex S.R.L. Device for a cell suspension culture
WO2024189527A1 (fr) * 2023-03-15 2024-09-19 Cellex S.R.L. Dispositif de culture en suspension de cellules pourvu d'un déviateur de flux

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Publication number Publication date
WO2012157007A8 (fr) 2013-03-14
ITTO20110432A1 (it) 2011-08-15

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