WO1989011899A1 - Systeme de recolte de produit de culture cellulaire a fibre creuse en tandem - Google Patents

Systeme de recolte de produit de culture cellulaire a fibre creuse en tandem Download PDF

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Publication number
WO1989011899A1
WO1989011899A1 PCT/US1989/002490 US8902490W WO8911899A1 WO 1989011899 A1 WO1989011899 A1 WO 1989011899A1 US 8902490 W US8902490 W US 8902490W WO 8911899 A1 WO8911899 A1 WO 8911899A1
Authority
WO
WIPO (PCT)
Prior art keywords
barrier
retentate
permeate
cross
separation means
Prior art date
Application number
PCT/US1989/002490
Other languages
English (en)
Inventor
William R. Tolbert
Chester S. Ho
Mark Baumgartener
Original Assignee
Invitron Corporation
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 Invitron Corporation filed Critical Invitron Corporation
Publication of WO1989011899A1 publication Critical patent/WO1989011899A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/147—Microfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D35/00—Filtering devices having features not specifically covered by groups B01D24/00 - B01D33/00, or for applications not specifically covered by groups B01D24/00 - B01D33/00; Auxiliary devices for filtration; Filter housing constructions
    • B01D35/12—Devices for taking out of action one or more units of multi- unit filters, e.g. for regeneration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/02—Membrane cleaning or sterilisation ; Membrane regeneration
    • 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
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/10—Separation or concentration of fermentation products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2321/00—Details relating to membrane cleaning, regeneration, sterilization or to the prevention of fouling
    • B01D2321/04—Backflushing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2321/00—Details relating to membrane cleaning, regeneration, sterilization or to the prevention of fouling
    • B01D2321/20—By influencing the flow
    • B01D2321/2083—By reversing the flow

Definitions

  • the invention relates to large scale fermenta ⁇ tion and cell culture methods.
  • it relates to methods of continuous cell culture and product harvest using a hollow fiber harvest system.
  • cross-flow separations involve passiner the dilute cell culture past a membrane (which may include—a planar, tubular or fiber membrane) wherein the product of the cell culture is able to transit the membrane but the particulates remain confined on one side of the membrane barrier.
  • the "filtrate" which is capable of transiting the barrier is recovered and the cell suspension, which is confined on the side of the membrane, where it has been introduced, is rediluted with medium and returned to the culture vessel. While this continuous approach greatly enhances the productivity of the cell culture, it is not without its own problems. The process can be continued only for a fairly brief period of time before the membrane becomes clogged because of intermedi ⁇ ate size particles present in the suspension. In order to continue the process, the membrane must either be replaced (which is expensive) or clarified by backflushing with the filtrate. Either approach introduces an inherent dis- continuity in the culture system.
  • the cartridge is disconnected from the culture vessel and the permeate is used to flow in the opposite direction from the outside of the membrane into the liwe and the backflushed material is discarded.
  • the backflushing medium has to be of "permeate quality", and backflushing of a portion of the permeate is suggested. It is clear that this approach creates a discontinuity as the entire cartridge is dis ⁇ connected from the culture vessel while cleaning takes place.
  • the invention disclosed herein is universally applicable to systems of cross-flow separations and effectively assures a continuous stream of product without waste of permeate for cleansing purposes.
  • the invention provides a tandem system whereby cell cultures can be maintained under conditions which provide for their healthy maintenance and product- producing capacity and which permit the continuous harvest of product.
  • the invention method accomplishes this by provia ⁇ ng * - at least two cross-flow filtration systems in tande ⁇ r,-thus permitting the maintenance in a functional condition of at least one cross filtration system continuously.
  • the use of the invention method prevents a disconnect of product harvest, and thus provides a constant product harvest which not only maintains cellular vigor, but also prevents decomposition of the product.
  • the invention is directed to a method to provide continuous cross-flow separation from an untreated dispersion of components of differing sizes, such as a cell culture suspension, which method comprises passing the untreated dispersion alternately through one of at least a first and second cross-flow separation means, and regenerating the other of said first or second means by reverse flow of a barrier-clearing fluid.
  • the dispersion to be treated is passed through the retentate side of the first cross-flow separation means to obtain a permeate and a retentate.
  • the permeate is withdrawn from the permeate side of the barrier, and the retentate returned to the source of the untreated dispersion.
  • the barrier-clear- ing fluid is passed from the permeate side of the barrier in the second cross-flow separation means, to be recovered from the retentate side.
  • the cycle is then repeated by activating the switching protocol so that the first cross-flow separation means is employed in the recovery of retentate and harvest of product, while the second separation means is subjected to backflow with bar ⁇ rier clearing fluid.
  • the cycles are repeated for an arbitrary number of times, thus maintaining a continuous procesTaring of the dispersion.
  • the invention is directed to apparatus suitable for conducting the method of the inven ⁇ tion.
  • Figure 1 shows a system for cross-flow filtra ⁇ tion and for its maintenance by discontinuous cleaning processes.
  • Figure 2 shows a diagram of a typical apparatus useful in the method of the invention.
  • cross-flow separation means refers to an apparatus or material into which is introduced a nonhomogeneous fluid mixture containing at least one component which is capable of transiting a bar- rier past which it is flowing and at least one other component which is retained on the same side of the bar ⁇ rier as that of its passage.
  • This initial mixture containing these inhomogeneous components will be referred to herein as the "untreated dispersion” .
  • the side of the barrier past which the untreated dispersion flows is designated the “retentate side of the barrier”; the other side is the “permeate side of the barrier”.
  • the cross-flow separation means comprises at least a barrier which effects the separation of the untreated dispersion into a "permeate" which has transited the barrier and a "retentate" which has not.
  • a barrier which effects the separation of the untreated dispersion into a "permeate" which has transited the barrier and a "retentate" which has not.
  • substantially all of the component incapable of transiting the barrier will be included in the retentate; depending on the efficiency of the separation, some of the components, including the fluid itself, which are capable of transiting the barrier may in fact be included in the retentate.
  • the permeate contains substantially only the components capable of barrier transition as well as the supporting fluid.
  • the barrier may vary both in composition and in physical form. Exemplified and preferred herein is a series of hollow fibers wherein the walls of the fibers constitute the barrier. It is preferred that the untreated dispersion be introduced into the lumen of the fibers so that the retentate remains in the interior of the fibers while the permeate passes through the fiber walls to the exterior. It is not impossible, although relatively impractical, to introduce the untreated disper ⁇ sion to the exterior of fibers contained in a cartridge and to harvest the permeate from their interior; the practicality of this approach increases as the diameter of the fiber approaches that of a tubule.
  • Other physical configurations include a series of flat panels wherein the interstitial spaces between the panels are not in physical communication. Other means for providing volumes separated by these semipermeable membrane barriers can also be—envisioned.
  • the material of the barrier must be such that it is, in regard to the components of the untreated disper ⁇ sion, a semipermeable membrane -- i.e., the pore size or other means of transit must be such that some components are capable of passing through the membrane while others are not.
  • the compositional nature of the barrier will therefore vary with the nature of the untreated disper ⁇ sion.
  • materials disclosed by the Brown et al reference cited above may be suggested. These materials include acrylic polymers, borosilicate glass, cellulose esters, polysulfones, sintered metals , polypropylenes, porcelains, cellulose acetates and nitrates.
  • the discrimination size can be varied.
  • materials generally employed for dialysis separation are useful. These include cellophane, polyvinylidene difluoride, microporous Teflon, polysulfones, cellulose derivatives and polyether sulfone.
  • the method and apparatus of the invention are applicable to a wide variety of untreated dispersions/barrier combinations.
  • Suitable untreated dispersions include not only cells suspended in media, but also a variety of dispersions encountered in various contexts such as sewage treatment, food processing, pharmaceutical and chemical manufacturing, isolation and purification of natural products, paper manufacture, recycling operations, and many others.
  • the method and apparatus of the invention are applicable to any process or protocol which involves, or advantageously could involve, cross-flow separation of the components in a liquid mixture based on size.
  • barrier-clearing fluid refers to a fluid which contains only components which are capable c-f readily transiting the barrier. If the untreated " dispersion is a cell culture suspension, a suit ⁇ able barrier-clearing fluid is fresh medium.
  • the apparatus of the invention comprises at least two interconnected compartments capable of effecting cross-flow separation of the components of the untreated dispersion.
  • the untreated dispersion is passed alternately through one or more of these compartments in a manner so as to effect cross-flow separation so that the larger components are retained on the retentate side of a barrier and the smaller ones pass through to the permeate side.
  • the barrier clearing fluid is passed from the permeate side of the barrier to be recovered from the retentate side. If the barrier- clearing fluid is heated prior to use, it may be advantageous to include a gas bleed connection on the permeate side of the barrier to prevent gas build up due to change in gas solubility of the fluid.
  • the roles of the various compartments are then repeatedly reversed.
  • the reversal cycles can be set up to be timed on an arbitrary schedule, which is preferably adjusted to effect the reversal as clogging begins to occur in the "separation" compartments, or can be triggered by the onset of the clogging. Both types of timing can be automated, the first simply using a timer; the second a sensor and response means. At each reversal, the "separation" compartment(s) become “barrier clearing" compartments, and vice versa.
  • the system illustrated in Figure 2 is designed for application of the invention process to a cell suspen ⁇ sion from a reactor.
  • the nature of the reactor is not critical to the method of the invention, and can be a simple shaker, stirred reactor, or static maintenance re ⁇ actor as described in U.S. patent 4,537,860 or may itself be a hollow fiber reactor as described in U.S. 4,201,845.
  • the barrier composition will differ between that in the product harvest apparatus shown in the figure and that in the reactor itself.
  • the configuration in Figure 2 is, of course, applicable to other untreated dispersions such as high MW protein solutions, particle size separations and the like, as set forth above.
  • the tandem separation units A and B are cartridges containing packages of hollow fibers whose walls are of appropriate pore size to permit the passage of product, but not of cells.
  • the inlet ports 1A and IB and outlet " ports 2A and 2B are in communication with the lumen of each of the packaged fibers.
  • the inlet ports 3A and 3B and the outlet ports 4A and 4B ere in communication with the surroundings and exterior surfaces of the fibers.
  • the system is controlled by a series of on/off valves labeled C1-C6.
  • the tandem separations and cleaning operations employ fluids from two sources: the untreated dispersion is pumped from the reactor by the pump PI as shown; the barrier-clearing fluid, which in this embodiment is identical with replacement medium is supplied by a second pump P2 as shown.
  • a third pump, P3, is employed to remove the permeate from the appropriate hollow fiber cartridge.
  • the series of valves C1-C6 provide a switching means to permit either A or B in one phase of a cycle to be provided with the untreated dispersion and the other to be in the barrier clearing phase.
  • An additional valve, C7 is common to both phases of each cycle and remains closed through normal operations. It permits the supply of additional medium to the reactor.
  • the switching means is configured as shown for condition 1 in the figure. Valves Cl, C4 and C5 will be open; valves C2, C3, C6 and C7 will be closed. Under this condition, the cell suspension will be pumped by PI through valve Cl into the inlet 1A for cartridge A and the retentate will continue through the lumen of the fibers through the outlet means 2A and through the attached conduit IT and then into the common conduit 3T for return to the reactor. Backflow through the medium-bearing conduit 4T is prevented because valve C7 is closed. The product which exits cartridge A throuqh the outlet 4A is permitted to pass by open valve C5 anri- is * pumped out of the system by the pump P3. Closed valve C2- " prevents flow through cartridge B.
  • cartridge B is sub ⁇ jected to barrier clearance using fresh medium using the medium pump P2.
  • Open valve C4 permits flow into cartridge B at inlet 3B which is in communication with the exterior of the fibers, closed valve C3 prevents flow into cartridge A.
  • valve C6 is closed, the medium is forced into the lumen of the fibers, carrying with it any "inter ⁇ mediate" size components which have lodged in the pores and the fluid exits through the outlet in communication with the fiber lumen, 2B, through the conduit 2T to merge with the retentate from cartridge A in conduit 3T for return to the reactor.
  • the incoming medium serves not only to clear the carrier in cartridge B, but also to replenish medium lost in the cross-flow separation in cartridge A.
  • the valve C7 can be opened if needed to provide additional replacement medium.
  • the apparatus is converted to condition 2 wherein the fibers of cartridge A will be cleared and those of cartridge B employed for product harvest. Under this condition, valves Cl, C4, C5 and C7 are closed, but valves C2, C3 and C6 are open. The functions of cartridges A and B are thereby reversed, and the second phase of the cycle is entered.
  • the cycle can, of course, be effected at arbitrary intervals and can be preset and automated. Suitable intervals for the duration of each phase of the cycle will vary with the untreated dispersion, the nature of the barrier, and the physical parameters of the apparatus. Suitable intervals for harvest of product from cell culture will vary from a few (e.g., 1-2) minutes to a few (e.g., 1-8) hours, to a few (e.g., 1-4) days for each phase.. These intervals can, of course, be set using a timer. —Intervals determined by condition of the barrier can also be automated by employing sensors and response means thereto.
  • the medium must therefore enter the lumen of the fibers carrying along with it the inter ⁇ mediate components embedded in the barrier, these particles are carried along with the clearing fluid through outlet 2A into conduit IT.
  • the fluid containing both intermediate particles and replacement medium then is combined with the effluent from the lumen of cartridge B in conduit 3T for return to the reactor.
  • the cycle can then be repeated an indeterminate number of times alternating cartridges A and B from separation phase to barrier clearing phase. At all times, the untreated cell suspension is subjected to uniform conditions of product harvest and media replacement.
  • FIG. 2 shows only one unit or cartridge for separation and one for barrier clearance, but, of course, cartridges A and B can be replaced by a multiplicity of units — two, three, several or dozens if needed. While it is preferred that the number of "A" units equal the number of "B" units, this is not a neces ⁇ sary csndition for practice of the invention. While the invention has been illustrated to show a preferred embodiment and to explain the manner of its operation, the invention is not limited thereby, but rather is defined by the following claims.

Abstract

On a mis au point un procédé d'extraction en continu de produit provenant d'une culture cellulaire ou d'exécution en continu d'autres séparations par courant transversal, permettant l'évacuation simultanée de la barrière de séparation. On emploie des séparateur (A, B) à courant transversal en tandem pour rétablir la barrière dans des processus cycliques, afin de conserver une efficacité continue de séparation.
PCT/US1989/002490 1988-06-08 1989-06-07 Systeme de recolte de produit de culture cellulaire a fibre creuse en tandem WO1989011899A1 (fr)

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Application Number Priority Date Filing Date Title
US20417488A 1988-06-08 1988-06-08
US204,174 1988-06-08

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Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0427376A2 (fr) * 1989-11-08 1991-05-15 Koch Membrane Systems, Inc Système de séparation à membrane et procédé de fonctionnement
US5066402A (en) * 1990-08-31 1991-11-19 Lyonnaise Des Eaux-Dumez Method of changing operating modes in automatic water filtering apparatus using tubular membranes
EP1354941A1 (fr) * 2002-04-19 2003-10-22 Computer Cell Culture Center S.A. Dispositif et procédé de culture de cellules dans un bioréacteur à concentrations cellulaires élevées
EP2113557A3 (fr) * 2008-04-29 2011-11-02 Chmiel, Prof. Dr.-Ing. habil., Horst Nettoyage in situ de membranes intégrées dans un bioréacteur
CN103189129A (zh) * 2010-10-27 2013-07-03 东丽株式会社 中空纤维膜过滤装置及中空纤维膜组件的清洗方法
US9738867B2 (en) 2012-03-15 2017-08-22 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US9745548B2 (en) 2012-03-15 2017-08-29 Flodesign Sonics, Inc. Acoustic perfusion devices
US9745569B2 (en) 2013-09-13 2017-08-29 Flodesign Sonics, Inc. System for generating high concentration factors for low cell density suspensions
US9752114B2 (en) 2012-03-15 2017-09-05 Flodesign Sonics, Inc Bioreactor using acoustic standing waves
US9783775B2 (en) 2012-03-15 2017-10-10 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US9796956B2 (en) 2013-11-06 2017-10-24 Flodesign Sonics, Inc. Multi-stage acoustophoresis device
US10106770B2 (en) 2015-03-24 2018-10-23 Flodesign Sonics, Inc. Methods and apparatus for particle aggregation using acoustic standing waves
US10322949B2 (en) 2012-03-15 2019-06-18 Flodesign Sonics, Inc. Transducer and reflector configurations for an acoustophoretic device
US10350514B2 (en) 2012-03-15 2019-07-16 Flodesign Sonics, Inc. Separation of multi-component fluid through ultrasonic acoustophoresis
US10370635B2 (en) 2012-03-15 2019-08-06 Flodesign Sonics, Inc. Acoustic separation of T cells
US10427956B2 (en) 2009-11-16 2019-10-01 Flodesign Sonics, Inc. Ultrasound and acoustophoresis for water purification
US10640760B2 (en) 2016-05-03 2020-05-05 Flodesign Sonics, Inc. Therapeutic cell washing, concentration, and separation utilizing acoustophoresis
US10662402B2 (en) 2012-03-15 2020-05-26 Flodesign Sonics, Inc. Acoustic perfusion devices
US10689609B2 (en) 2012-03-15 2020-06-23 Flodesign Sonics, Inc. Acoustic bioreactor processes
US10704021B2 (en) 2012-03-15 2020-07-07 Flodesign Sonics, Inc. Acoustic perfusion devices
US10710006B2 (en) 2016-04-25 2020-07-14 Flodesign Sonics, Inc. Piezoelectric transducer for generation of an acoustic standing wave
US10724029B2 (en) 2012-03-15 2020-07-28 Flodesign Sonics, Inc. Acoustophoretic separation technology using multi-dimensional standing waves
US10737953B2 (en) 2012-04-20 2020-08-11 Flodesign Sonics, Inc. Acoustophoretic method for use in bioreactors
US10785574B2 (en) 2017-12-14 2020-09-22 Flodesign Sonics, Inc. Acoustic transducer driver and controller
US10814253B2 (en) 2014-07-02 2020-10-27 Flodesign Sonics, Inc. Large scale acoustic separation device
US10953436B2 (en) 2012-03-15 2021-03-23 Flodesign Sonics, Inc. Acoustophoretic device with piezoelectric transducer array
US10967298B2 (en) 2012-03-15 2021-04-06 Flodesign Sonics, Inc. Driver and control for variable impedence load
US10975368B2 (en) 2014-01-08 2021-04-13 Flodesign Sonics, Inc. Acoustophoresis device with dual acoustophoretic chamber
US11007457B2 (en) 2012-03-15 2021-05-18 Flodesign Sonics, Inc. Electronic configuration and control for acoustic standing wave generation
US11021699B2 (en) 2015-04-29 2021-06-01 FioDesign Sonics, Inc. Separation using angled acoustic waves
US11085035B2 (en) 2016-05-03 2021-08-10 Flodesign Sonics, Inc. Therapeutic cell washing, concentration, and separation utilizing acoustophoresis
WO2021198678A1 (fr) * 2020-03-31 2021-10-07 Quanta Dialysis Technologies Ltd Optimisation de la performance d'un appareil de dialyse
US11214789B2 (en) 2016-05-03 2022-01-04 Flodesign Sonics, Inc. Concentration and washing of particles with acoustics
US11377651B2 (en) 2016-10-19 2022-07-05 Flodesign Sonics, Inc. Cell therapy processes utilizing acoustophoresis
US11420136B2 (en) 2016-10-19 2022-08-23 Flodesign Sonics, Inc. Affinity cell extraction by acoustics
US11459540B2 (en) 2015-07-28 2022-10-04 Flodesign Sonics, Inc. Expanded bed affinity selection
US11474085B2 (en) 2015-07-28 2022-10-18 Flodesign Sonics, Inc. Expanded bed affinity selection
US11708572B2 (en) 2015-04-29 2023-07-25 Flodesign Sonics, Inc. Acoustic cell separation techniques and processes

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Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0427376A3 (en) * 1989-11-08 1992-09-02 Romicon, Inc. Membrane separation system and method of operation
EP0427376A2 (fr) * 1989-11-08 1991-05-15 Koch Membrane Systems, Inc Système de séparation à membrane et procédé de fonctionnement
US5066402A (en) * 1990-08-31 1991-11-19 Lyonnaise Des Eaux-Dumez Method of changing operating modes in automatic water filtering apparatus using tubular membranes
EP1354941A1 (fr) * 2002-04-19 2003-10-22 Computer Cell Culture Center S.A. Dispositif et procédé de culture de cellules dans un bioréacteur à concentrations cellulaires élevées
WO2003089567A2 (fr) * 2002-04-19 2003-10-30 Henogen S.A. Appareil et procede de culture cellulaire dans un bioreacteur a concentration cellulaire elevee
WO2003089567A3 (fr) * 2002-04-19 2004-03-18 Henogen S A Appareil et procede de culture cellulaire dans un bioreacteur a concentration cellulaire elevee
EP2113557A3 (fr) * 2008-04-29 2011-11-02 Chmiel, Prof. Dr.-Ing. habil., Horst Nettoyage in situ de membranes intégrées dans un bioréacteur
US10427956B2 (en) 2009-11-16 2019-10-01 Flodesign Sonics, Inc. Ultrasound and acoustophoresis for water purification
CN103189129A (zh) * 2010-10-27 2013-07-03 东丽株式会社 中空纤维膜过滤装置及中空纤维膜组件的清洗方法
US10662404B2 (en) 2012-03-15 2020-05-26 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US10724029B2 (en) 2012-03-15 2020-07-28 Flodesign Sonics, Inc. Acoustophoretic separation technology using multi-dimensional standing waves
US9752114B2 (en) 2012-03-15 2017-09-05 Flodesign Sonics, Inc Bioreactor using acoustic standing waves
US9783775B2 (en) 2012-03-15 2017-10-10 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US11007457B2 (en) 2012-03-15 2021-05-18 Flodesign Sonics, Inc. Electronic configuration and control for acoustic standing wave generation
US10967298B2 (en) 2012-03-15 2021-04-06 Flodesign Sonics, Inc. Driver and control for variable impedence load
US10953436B2 (en) 2012-03-15 2021-03-23 Flodesign Sonics, Inc. Acoustophoretic device with piezoelectric transducer array
US10322949B2 (en) 2012-03-15 2019-06-18 Flodesign Sonics, Inc. Transducer and reflector configurations for an acoustophoretic device
US10350514B2 (en) 2012-03-15 2019-07-16 Flodesign Sonics, Inc. Separation of multi-component fluid through ultrasonic acoustophoresis
US10370635B2 (en) 2012-03-15 2019-08-06 Flodesign Sonics, Inc. Acoustic separation of T cells
US9745548B2 (en) 2012-03-15 2017-08-29 Flodesign Sonics, Inc. Acoustic perfusion devices
US10947493B2 (en) 2012-03-15 2021-03-16 Flodesign Sonics, Inc. Acoustic perfusion devices
US10662402B2 (en) 2012-03-15 2020-05-26 Flodesign Sonics, Inc. Acoustic perfusion devices
US9738867B2 (en) 2012-03-15 2017-08-22 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US10689609B2 (en) 2012-03-15 2020-06-23 Flodesign Sonics, Inc. Acoustic bioreactor processes
US10704021B2 (en) 2012-03-15 2020-07-07 Flodesign Sonics, Inc. Acoustic perfusion devices
US10737953B2 (en) 2012-04-20 2020-08-11 Flodesign Sonics, Inc. Acoustophoretic method for use in bioreactors
US10308928B2 (en) 2013-09-13 2019-06-04 Flodesign Sonics, Inc. System for generating high concentration factors for low cell density suspensions
US9745569B2 (en) 2013-09-13 2017-08-29 Flodesign Sonics, Inc. System for generating high concentration factors for low cell density suspensions
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