KR101629877B1 - Multi plane mixer and separator (mpms) system - Google Patents

Abstract

The present disclosure provides a multi-planar mixer and separator (MPMS) system. The system includes a base frame of a predetermined shape configured to form a base for an MPMS system. The motor is mounted to the base frame to rotate the MPMS system. The ball joint mechanism is fixed to the motor using a link and the other end of the ball joint mechanism is coupled to the fork. The container holding frame is connected to the fork using bars, and the container holding frame can be inclined upward by 120 DEG with respect to the base frame. In addition, MPMS containers of predetermined shapes are removably mounted to the container holding frame for mixing fluids of different densities.

Description

[0001] MULTI PLANE MIXER AND SEPARATOR (MPMS) SYSTEM [0002]

Embodiments described herein relate to stirrers / mixers, and more particularly to multi-planar mixer / separator systems for performing additional functions such as mixing functions and phase separation, settling, distribution, and the like.

Mixing means treating a heterogeneous system to obtain a more homogeneous system. Stirring is one way to achieve mixing. Heat exchange and mass transfer can occur by mixing. The equipment used in the process of mixing multiple liquids or solids uses a tank / vessel / flask. The mixing process is to apply a predetermined amount of shear force to the material to be mixed.

The equipment used for mixing is called mixers. Mixers differ in their structures according to the desired output and the constraints involved in obtaining the output. The mixer generally disperses one phase (liquid, solid, gas) into the main continuous phase. The rotor or impeller is used in a tank containing a solution to be mixed with a fixed part known as a stator, or in a pipe through which the solution passes. Using an impeller or rotor produces a shear force that allows homogenization of the two different materials. For example, high shear mixers can be used to produce emulsions, suspensions, lyazoles (dispersed in liquid) and granular products. High-shear mixers are used for emulsification, homogenization, particle size reduction and distribution in the adhesive, chemical, pharmaceutical and plastics industries.

Alternatively, the mixer may have a stirrer, which is connected to a motor that drives the stirrer to stir the material at the required rate. The stirrer can include multiple blades and is rotated clockwise or counterclockwise using a motor to mix liquids or solids. In a conventional method, liquids with different densities are mixed by moving liquids from top to bottom and vice versa, so that the pattern in which the liquid is mixed due to the stirrer having only one degree of freedom of movement is simple Pattern. In order to achieve uniform mixing, a strong stirrer is induced through a high-speed stirrer, resulting in a high-intensity turbulence, which speeds up the speed of the moving particles and adds a higher shear force to the molecules. Certain combinations of pressure and vacuum can cause circulation and shear deformation of the liquid in the container. When mixing is performed without pressure and vacuum, sufficiently combined vertical and lateral movement can be achieved economically using liquid mixing vessels having suitable dimensions, specificities and internal structures. The dimensions, ratios, and internal structures of the liquid mixing vessels need to be selected to meet the needs in the application, for example, when different concentrations of liquid need to be homogeneously mixed.

Various types of mixers are also used in biology laboratories and biotechnology industries, examples of which include vortex mixers. The vortex mixer is composed of an electric motor having a drive shaft arranged in a vertical direction, and a cup-shaped rubber piece mounted on the drive shaft slightly deviates from the center. As the motor starts to operate, the rubber piece undergoes circular motion and shakes rapidly. When a test tube or other suitable container is pressed into the rubber cup, the movement is transferred to the liquid inside and a vortex is generated.

Another example of a laboratory device is a magnetic stirrer or magnet mixer that uses a rotating magnetic field to rapidly rotate a stuffed bar immersed in a liquid to stir the liquid. The rotating field may be generated by a rotating magnet or a set of stationary electromagnets installed at the bottom of the vessel containing the liquid. Generally, the magnet stirrer includes a hot plate or other means for heating the liquid. Another example of a laboratory device includes a homogenizer, an orbital shaker, and the like.

Current mixers disclosed in the prior art are known to generate high speed, turbulence, shear stress and bubbles. All of these factors can damage biochemical / biocompatible components and are therefore undesirable in the biotechnology and biomedical industries. For example, some biochemical constructs such as proteins can be oxidized or denatured by bubbles. Turbulence can be particularly disadvantageous in the process of mixing live biological samples such as cells and tissues that can be damaged by shear forces. For now, the effects of shear and turbulence can be reduced by external additives such as mild surfactants. In biological samples, the use of such an additive is undesirable because it may be toxic.

Given the above, there is a need to provide an improved system for effective mixing. The present specification relates to a multipurpose system for mixing at least two identical or different phases without any turbulence or bubbles and capable of performing phase separation, settling and distribution functions as necessary after the mixing process.

The embodiments described herein provide an automated system that can operate in multiple planes and perform a number of functions, and additional advantages are obtained by providing a system as claimed herein.

Additional features and advantages are realized through the teachings herein. Other embodiments and aspects of the disclosure are contemplated as part of the invention as described and claimed herein.

One embodiment described herein provides an automatic multi-planar mixer and separator (MPMS) system capable of performing various functions. The system includes a base frame of a predetermined shape configured to form a base of the MPMS system. The motor is mounted to the base frame to rotate the MPMS system. The ball joint mechanism is fixed to the motor using a link and the other end of the ball joint mechanism is coupled to a folk. The fork is a Y-shaped fork and one cross bearing is fixed to the upper ends of the fork's limb. The container holding frame is connected to the fork using bars, and the container holding frame can be inclined at an angle of 120 DEG to the base frame or at any angle determined by the user. The system also includes a container or MPMS container of a predetermined shape that can be removably mounted to the container holding frame.

 In one embodiment described herein, a pair of bars are mounted to the base frame, at least one cross-bearing cup is fixed to the upper end of each bar using cross links, the cross bearings on the bars and the forks Form a universal joint.

In one embodiment described herein, at least one position sensor is provided on the ball joint mechanism to measure the position of the ball joint mechanism, and the position sensor is interfaced with the controller.

In one embodiment described herein, a straight bearing with a bush bearing is coupled to the container holding frame using a link assembly to tilt the container holding frame upward by 120 DEG with respect to the base frame.

In one embodiment described herein, the link assembly includes a pair of first and second links that constitute a rotating treatment, and the motor is coupled to the linear bearing to selectively raise and lower the MPMS container frame, Is interfaced with the controller.

 In one embodiment described herein, at least one position sensor is provided on the container holding frame to control the elevation angle of the MPMS container, and the position sensor is interfaced with the controller.

In one embodiment described herein, the motor is interfaced with the controller, and the speed and direction of rotation of the motor are controlled by the controller as needed.

In one embodiment described herein, the MPMS container includes a curved top surface and a flat bottom surface, and the flat bottom surface of the MPMS container is pre-determined with a predetermined profile to enable homogeneous mixing without generating turbulence or shear forces And a plurality of projections arranged in a determined pattern. The shape of the projections is at least one of a triangle, a square, a rectangle, a circle, an ellipse, and a baffle.

In one embodiment described herein, an MPMS container includes a semicircular inlet and a funnel-shaped outlet, wherein at least one valve is interfaced with the controller to control the flow of components entering and exiting the MPMS container.

In one embodiment described herein, the MPMS system is optionally housed in a chamber, the MPMS container is optionally aseptic and preferably aseptic for a biological sample, and at least one temperature sensor is provided within the chamber And the temperature sensor is interfaced with the controller to control the temperature in the chamber within a predetermined limit. When the temperature sensor can not contact the mixed media, an adjustment method using a control circuit is used to manage the desired temperature.

In one embodiment described herein, the container holding frame is rotated both clockwise and counterclockwise by a motor and a ball joint mechanism. The container holding frame is also programmed to rotate along any plane.

In one embodiment described herein, the container holding frame can be programmed to rotate along any desired angle and plane.

The foregoing summary is exemplary only and is not intended to be limiting in any way. In addition to the exemplary aspects, embodiments, and features described above, additional aspects, embodiments, and features will become apparent with reference to the accompanying drawings and the following detailed description.

The features and characteristics described herein are set forth in the appended claims. The description itself, however, will be best understood by reference to the following detailed description of illustrative embodiments, which is to be read in connection with the accompanying drawings, together with a preferred mode of use, further objects and advantages. One or more embodiments are now described, by way of example only, with reference to the accompanying drawings, wherein like numerals denote like elements, wherein:
Figure 1A is a perspective view illustrating the MPMS system described herein.
1B is an exploded view of an enlarged view of the MPMS system.
2 is a block diagram illustrating an MPMS system embedded in a chamber.
Figures 3a and 3b are perspective and bottom views illustrating the MPMS container described herein.
Figures 4 (a) - (d) illustrate various planar locations of an MPMS vessel mixing liquids of differing densities.
Figure 4 (e) shows the position of the MPMS container when the container holding frame is inclined at 90 [deg.] To the base frame.
Figure 5 shows a substrate vessel fraction (SVF) treatment device in combination with an MPMS system.
The drawings illustrate embodiments for illustrative purposes only. Those of ordinary skill in the art will readily appreciate from the following description that alternative embodiments of the structures and methods illustrated herein may be used without departing from the principles set forth herein.

The embodiments described herein are automatic multi-planar mixer and separator (MPMS) systems having a variety of uses such as phase separation, settling, dispensing, etc. as needed after mixing and mixing of components / compositions. The system can be used in any industry where mixing of two materials / components / compositions is required. More specifically, the system can be used in areas where the mixing of materials / components / components needs to be performed without generating turbulence or shear forces. Some examples of industries in which the mixing of components is carried out without turbulence or shear are generally found in the biotechnology, biomedical and biochemical industries where live cells or biological samples are used or processed.

One area of use of the MPMS system as described herein are the biotechnology and biomedical industries where the processing of biological samples is required. The processing of samples can be done for a number of reasons, such as sampling, testing, production of biological products, cell-based products, separation, cultivation, etc. One function of the mixing or MPMS system can be used effectively to obtain the desired output .

The biological sample may include biological tissue, cells, and any other biological components. Examples of living tissues include, but are not limited to, fat, placenta, synovial tissue, umbilical cord, cord blood, bone marrow, liver, pancreas, and the like. Mixing of biological samples can be done for a number of purposes, most of which do not require turbulence.

Different types of biomixers that can be performed by an MPMS system,

Uniform mixing of multiple miscible or immiscible liquids;

- dissolving the solute in a solvent;

Suspension of the particulate solids in the liquid;

- washing of biotissues with buffer solution;

- degradation / dissociation of biotissues using a buffer solution containing degrading enzymes;

Suspensions of biological entities such as cells, viruses and the like into a buffer solution / medium; And

- antibody-attached beads for differential isolation / selection / recovery / purification / purification of specific / desired biological constituents such as growth factors, cytokines, proteins or cell groups from a liquid mixture or suspension -coated beads, or a mixture of affinity substrates.

The MPMS system described herein is configured to mix biological samples without turbulence, but can also be used when turbulence is required.

The second functional aspect of the MPMS system is phase separation,

Separation of a mixture of a plurality of miscible liquids that have undergone physical and chemical interactions during the mixing process, such as the separation of an aqueous buffer fraction containing debris from, for example, adipose tissue; And

- buoyancy densities include, but are not necessarily limited to, separation of different biological tissues (e.g., fat and blood).

A third functional aspect of the device described herein is a settling,

Sedimentation of cells from suspensions which may include living tissue such as bone marrow / cord blood, or sedimentation of cells suspended in media / buffers / other preparations known in the art; And

- selecting / recovering / purifying / purifying certain biological components such as blood, bone marrow, umbilical cord or digested tissue such as growth factors, cytokines, proteins or cell groups from a liquid mixture or suspension Including, but not limited to, sedimentation of the microparticle / affinity matrix complex.

As a fourth functional embodiment, it is necessary to uniformly distribute the cells / solids / fine particles, etc. into different containers of a predetermined volume.

The foregoing has broadly outlined the features and technical advantages described herein for a better understanding of the details of the disclosure herein below. Additional features and advantages forming the subject matter of the claims set forth herein will be described below. It is to be understood by those of ordinary skill in the art that the disclosed concepts and specific embodiments may be readily utilized as a basis for designing or modifying other structures for carrying out the objects disclosed herein. Equivalent structures that do not depart from the spirit and scope of the invention disclosed in the accompanying claims are also realized by those skilled in the art. BRIEF DESCRIPTION OF THE DRAWINGS The novel features believed characteristic of the invention, together with further objects and advantages, as to its organization and method of operation, will be better understood from the following detailed description when considered in conjunction with the accompanying drawings. It should be clearly understood, however, that each of the figures is provided for illustrative purposes only and is not intended to be limiting of the disclosure herein.

In particular, the present specification relates to MPMS systems, and more specifically to MPMS systems used to mix liquids of varying densities.

 FIGS. 1A and 1B are a perspective view and an exploded view illustrating an MPMS system 100 in accordance with the exemplary embodiment described herein. The system 100 described herein includes a base frame 101 of a predetermined shape configured to form a base of the system 100. The base frame 101 may be made of any material selected from the group including metals or non-metals, but is not limited thereto. The motor 102 is mounted on the base frame 10 of the MPMS system 100 to rotate and mix the MPMS system 100. Preferably, the motor 102 is a DC motor to vary the speed by regulating the voltage or current. The revolutions per minute (RPM) of the motor 102 is determined by the desired mixing speed. The system includes a ball joint mechanism 103 wherein one end of the ball joint mechanism 103 is fixed to the motor 102 via the adjustable link 104 and the other end is fixed to the fork 105. [ The adjustable link 104 may vary within a range of 0 to 30 mm depending on the angle required in the blend. The ball joint mechanism 103 includes ball and socket joints, which have a sliding fit that helps generate multi-plane motion. The fork 105 is a Y-shaped fork, and one cross bearing cup 108 is coupled to each upper end of the fork 105 to achieve a predetermined angular movement of the MPMS system 100. The system 100 also includes a pair of bars / pillars 107 mounted on the base frame 101 and at least one cross bearing cup 108 is mounted on the upper end of each bar 107 to form cross links 107a ). The cross bearing 106 is wrapped in a cross bearing cup 108 coupled to the forks 105 and the lower bars / pillars 107 to form a universal joint so that the MPMS system 100 can be rotated Converts the plane motion of the joint mechanism into multi-plane motion.

The container holding frame 110 is pivotally coupled on the cross link 109 to hold the MPMS container 112 and the cross link 109 is connected to the upper bars / pillars 111 Shaped fork 105. The Y- The container holding frame 110 is configured to be inclined upward by 120 DEG with respect to the base frame, and this angle can be changed according to the requirements of the user. In an embodiment in which a phase separation process is required after mixing, the container holding frame 110 may be inclined upwardly by 90 [deg.]. The system described herein has a container, called MPMS container 112. The MPMS container 112 has a predetermined shape and is detachably mounted on the container holding frame 111 for mixing.

In one embodiment described herein, the motor 102 interfaces with the controller 218 (see FIG. 2) to control the rotational speed and direction of rotation of the motor 102 as needed. The speed and direction of the motor 102 are determined by the mixing speed. The container holding frame 110 can be rotated in both the clockwise direction and the counterclockwise direction and is controlled by the controller 218. [

 The MPMS system 100 also includes a linear bearing 113 having a bush bearing 114 coupled to the container holding frame 110 using a link assembly 115 to move the container holding frame 110 to the base frame 110. [ It can be inclined upwards by 90 degrees with respect to the base 101. The link assembly 115 includes a pair of first and second links that make up a revolute pair. The linear bearing 113 is coupled to the motor 116 to selectively raise and lower the MPMS vessel 112. In addition, at least one position sensor 221 as shown in FIG. 2 is provided in the container holding frame 110 to control the elevation angle of the MPMS container 112. In one embodiment described herein, the motor 116 and the position sensor 221 are interfaced with the controller 218 as shown in FIG.

In one embodiment described herein, the container holding frame 110 is configured to be tilted upward by 120 degrees with respect to the base frame 101. In order to achieve a 120 deg. Tilt of the container holding frame 110, motors 116 with longer lead screws, higher torque and power ratings, differently sized links 115 are placed in the MPMS system 100 . The 120 deg. Tilt of the container holding frame 110 is used in the above-mentioned field including, but not necessarily limited to, fractional distillation and partial phase separation to release various liquids from a plurality of discharge ports of the container 112 .

In one embodiment described herein, the MPMS container 112 includes locking means for locking the MPMS container 112 to the container holding frame 110. The locking can be accomplished via any suitable locking mechanism, and in one embodiment of the present invention, the MPMS container 112 includes side ribs and J-shaped clamps for resiliently locking the MPMS container 112 to the container holding frame 110 .

2 is a block diagram illustrating an MPMS system 200 in accordance with the exemplary embodiment described herein. The MPMS system 200 is embedded in the chamber in a temperature controlled environment. At least one temperature sensor 220 is provided in the chamber 219 to measure the temperature in the chamber 219 and the temperature sensor 220 is interfaced with the controller 218 to control the temperature in the chamber 219 to a predetermined limit Lt; / RTI > In one embodiment described herein, the chamber 219 may be any suitable means selected from the group including, but not limited to, hot air circulation, infrared use, heating appliances or other means known in the art to which the invention pertains Gt; 37 C. < / RTI >

3A and 3B are a perspective view and a bottom view illustrating the MPMS container 112 according to the exemplary embodiment described herein. The MPMS container 112 includes a curved top surface 112a and a flat bottom surface 112b. The flat bottom surface 112b of the MPMS vessel 112 includes a plurality of projections 117 arranged in a predetermined pattern with a predetermined profile to enable homogenous mixing without generating turbulence or shear forces. The protrusions 117 will slow down the velocity of the liquid in the vessel 112 and thus the laminar motion will be maintained. The size, distance, angle and arrangement pattern of the projections improve the homogeneous mixing of the fluids. The size, distance, and angle of the protrusions 117 will vary depending on the need to perform the mixing as well as the arrangement of the protrusions 117 and the homogeneous mixing.

 In one embodiment described herein, the shape of the protrusions 117 is selected from the group including but not limited to triangular, square, rectangular, circular, elliptical and baffle types. The MPMS vessel 112 further includes a semicircular inlet 112c and a funnel-shaped outlet 112d at both ends of the MPMS vessel 112. The semi- The inlet 112c is configured to receive an input / substance that enters the MPMS vessel 112 for mixing and the outlet 112d is configured to discharge the product for further processing. In one embodiment described herein, a laminar flow will be made by a semicircular portion provided at the inlet of the MPMS vessel 112. The funnel-shaped portion provided at the outlet of the MPMS vessel 112 enables effective layer separation. In other embodiments, the outlet may be other shapes including, but not necessarily limited to, semicircular, elliptical, rectangular, and the like. The inlet and outlet valves are controlled by pinch valves.

The MPMS vessel 112 can be made of any material selected from the group including, but not limited to, non-metals and metals. In one embodiment described herein, the MPMS container 112 is made of rigid plastic such as polypropylene or polystyrene. The MPMS container 112 may optionally be made aseptically. Preferably, the MPMS container 112 may be made aseptic for living tissue. The dimensions of the MPMS container 112 are determined according to the field of use.

For example, Table 1 below shows various aspect ratios of the MPMS vessel 112. However, the dimensions provided in Table 1 are exemplary only and should not be construed as limiting MPMS. The dimensions of the container can be varied as needed.

Length of container (mm) Width of container (mm) Height of container (mm) Volume of container (ml) 420 160 35 1200 400 150 35 970 365 135 35 730 335 115 35 520 280 90 35 300

Figures 4A-4D illustrate that the MPMS system 400 in accordance with the exemplary embodiment described herein is in various planar positions during mixing.

Plane movement

The MPMS system 100 of FIG. 1 will be rotated by the motor 102. The motor 102 will rotate the ball joint mechanism 103 through the link 104. The balls and sockets in the ball joint mechanism will form sliding pits that help to convert planar motion into multi-plane motion. The fork 105 connected to the ball joint mechanism 103 is connected to the cross bearings 106 by forming a universal joint with the cross bearing cups 108 mounted on the lower bars / pillars 107 on the upper ends thereof. Bearing cups 108 for receiving the rotational movement of the fork 105 from the motor through the upper pillars / bars 111 coupled with the cross bearing cups 108 of the fork 105 to the container holding frame 110 . When the ball joint mechanism 103 causes a planar motion, the fork 105 causes multi-planar motion. The MPMS container 112 mounted on the container holding frame 110 will be rotated at various plane positions for various mixing results. Figures 4 (a) - (d) illustrate a state in which the system 400 of the present invention is in different planar positions.

FIG. 4 (e) is a perspective view showing a state in which the MPMS container 115 according to the exemplary embodiment described in FIG. 1 is in phase separation. After mixing, the controller 218 (see FIG. 2) will actuate the stirring and elevating motor 116, if necessary, and the motor 116 will rotate the linear bearing 113 accordingly. The bush bearing 114 connected to one end of the straight bearing 113 will push the link assembly 115. The link assembly 115 serving as a rotating treatment will vertically raise the container holding frame 110 to 90 占 with respect to the base frame 101 for phase separation. The position sensors 422 provided on the container holding frame 110 (as shown in Figure 4E) will be interfaced with the controller 218. The position sensors 422 will measure the position of the container holding frame 110 and when the desired position is reached the controller 218 will stop the stirring and elevating motor 116. A representative example of phase separation is shown in Figure 4e.

In one aspect described herein, the MPMS system 100 operates in accordance with the principles of a cam and a rotary joint mechanism. The MPMS system 100 is operated by a cam mechanism on a single swirling mechanism driven by a motor. The MPMS vessel 112 is held on a collar and bushing along the x-axis and performs a partial rotational movement through the motor 102.

excuse

The operation of the MPMS system is illustrated by way of example. However, this example should not be construed as defining an MPMS system. In this example, the MPMS system is used to process biological samples. However, the same MPMS system can also be used to process non-biological samples.

The MPMS system can be used to phase-separate tissue from the aqueous lower layer after mixing tissue with another buffer solution and stirring the mixture in a Stromal Vascular Fraction (SVF) treatment device 500.

5A illustrates an SVF processing apparatus 500 in combination with the MPMS system 501 described herein. The SVF processing apparatus 500 comprises a suitably configured chamber 517 or cover, and the chamber 517 may be transparent or opaque. The chamber 517 has a user interface with an LCD display and input buttons for inputting the parameters required to process the sample. The interface 505 is very user friendly and is programmed to adjust the settings of the device.

The SVF processing unit 500 includes buffer and enzyme vessels / units 506, an MPMS system 100 and a cell concentration unit 503. The geometry of the chambers / units may be varied, but is not necessarily limited to, a cubic shape, a square, a rectangle, a cylinder, and other known geometric shapes that can be used to achieve the purpose. An MPMS system 100, also referred to as a tissue processing unit, is attached to a rotation / stirring mechanism / MPMS assembly. The apparatus also includes one or two metering pumps 512 for supplying fat tissue obtained by liposuction from the patient for treatment to the MPMS system 100 and discharging liquids after phase separation. The chamber / unit 517 is made of rigid or semi-rigid nonreactive plastics such as polyvinyl, polycarbonate, or similar materials of physicochemical composition, but is not limited thereto.

Surgical tissue samples are delivered to the MPMS system 100 / tissue processing unit using a variety of commercially available liposuction devices to provide maximum flexibility to the surgeon, And is configured to accommodate various liposuction containers commonly used in the process. Once the inlet tube is connected to the device via tubes and adapters, the sample is pumped to the MPMS system 100 using a metering pump 504 for cleaning and disassembly. One-time sterilization containers 506 are used to accommodate buffers containing wash buffers and degrading enzymes. These vessels 506 have a predetermined type of outlets and are connected to the pinch valve 511 using a suitable tube during normal operation. Each of the vessels 506 is configured to receive a predetermined amount of liquid within a range of about 0.5 liters to about 10 liters. The next task in this process is to pump a pre-determined volume of buffer from one of the buffer containers 506 using the metering pump 512 by actuating the second valve of the pinch valve controller. The predetermined volume is equal to the amount of adipose tissue being treated. The volume is calculated based on the diameter and time of the tube and is input to the electronic circuitry of the user interface 511 using the data entry keyboard. When the desired volume is reached, pumping stops.

The MPMS vessel is then agitated for a period of 2 to 15 minutes by powering the motor arm of the MPMS system 100. The motor-driven arm connected to the motor delivers a uniform pitch and amplitude so that complete mixing of the samples can be achieved. After mixing, the MPMS vessel 112 can be vertically tilted and held stationary for a period of 2 to 15 minutes, so that the two phases begin to separate (the fat-rich upper and lower aqueous phases are clearly distinguished Lt; / RTI > Generally, a predetermined volume of the lower aqueous phase, which is 95% of the initial loading volume of the buffer, is discharged by operating the outlet port and valve, and the cleaning solution is collected in the waste storage tank. Filters (or mesh of 100-200 microns) can be drained to prevent the fat-rich layer from being discharged at this stage. This washing step is repeated three to four times to completely remove blood cells from the tissue.

The degradation step in the process is initiated by adding the same volume of pre-warmed buffer to the specified limit, containing a combination of collagenase or collagenase, pepsin, trypsin, papain or similar protein hydrolase. The enzyme / buffer solution fed from one of the two vessels is pumped through the third valve of the pinch valve using a metering pump.

The clamping device for holding the MPMS container 112 in place has a thermal pad that warms the contents of the MPMS container 112 when activated. The thermal control mechanism is adjusted to fully and uniformly heat the inside of the liquid to 37 °. Sensors coupled to the temperature controller maintain a constant temperature throughout the decomposition process. In order to increase the efficiency and uniformity of the degradation, the motor drive arm is actuated to allow the enzyme to smoothly and thoroughly mix with the adipose tissue throughout this process. Based on the volume of tissue and the concentration of enzymes used, degradation with continuous mixing is carried out for a minimum of 30 to 60 minutes. At the end of the digestion process, a pre-calculated amount of plasma is pumped to deactivate the enzyme using the same liquid handling network used to transfer the enzyme / buffer mixture. In another embodiment, an enzyme inhibitor that is not limited to ETGA or similar chemical composition inhibitors is added to deactivate the enzyme. In another embodiment, the enzymes are not inactivated because the global cleansing of the degraded cells is sufficient to completely remove the enzymes. Finally, after the motor drive arm is stopped, the operation of the thermal pad is stopped and the module is stopped for 2 to 10 minutes. The MPMS vessel 112 is then tilted 90 [deg.] With respect to the base to cause phase separation between the fat and aqueous fractions to occur. After the phase separation process, the wash solution is discharged to the waste reservoir 514 using a predetermined outlet, the outlet used for discharge being controlled by a valve having a one-way flow (from inside to outside). The cell slurry from the MPMS system 100 is also fed to the cell concentration unit / assembly 503 via an outlet for further processing.

The cell concentration unit / assembly 503 is selected from the group including, but not necessarily limited to, simple filtration, pressure filtration, vacuum assisted filtration, or combinations thereof. Optionally, the cell concentrating unit / assembly 503 receives a drive mechanism that enables controlled rotation of the chamber. The drive mechanism may be of a magnetic, mechanical, electromechanical or a combination thereof. The configuration and structure of the chamber also includes a vibrating mechanism to remove cells and debris that clog the filter. Independently or jointly, these devices increase the flow rate, prevent clogging of the filter material and enable cell concentration.

The above examples are presented for illustrative purposes only and the MPMS system can be used to mix non-biological samples including, but not limited to, any liquids, liquids, and solids.

Equivalents

Herein, for the use of substantially constant plural / singular terms, one of ordinary skill in the art will be able to appropriately translate from the plural to the singular and / or from singular to plural depending on the specification and / or application. The various permutations will be explicitly described herein for clarity.

In general, terms used herein and in particular in the appended claims (e.g., the text of the accompanying claims) generally refer to terms such as "open" Is interpreted as "including but not limited to" and the term "having" is interpreted as having "at least" and the term "includes" Will be understood by those of ordinary skill in the art to be used as " includes but not limited to "). It is also to be understood by those of ordinary skill in the art that a specific number of the recited claims is intended to be clearly stated in the claims and that such intent is not intended to be so. For example, to assist understanding, the following claims are hereby incorporated by reference to the introductory phrase "at least one ", and" one or more " . ≪ / RTI > It should be understood, however, that even if the same claim uses an adverbial term such as " one or more "or " at least one & an "and / or" an "are usually to be interpreted to mean " at least one" or " one or more "), Quot; an "or" an "is to be construed as an invention including at least one such description, and as being construed to mean limiting certain specific claims containing the recitation of the claims so set forth The same shall apply to the case where a definite article is used to start the writing of claims. Moreover, it is to be understood that, although specific numbers are recited in describing the claimed claims, those of ordinary skill in the art will understand that such descriptions are generally construed to mean at least the commonly recited number (e.g., Quot; bare " of a " two recitation "typically means at least two substrates, or two or more substrates). Furthermore, in those instances where a similar convention is used, such as at least one of A, B, and C, generally such a structure is a meaning of consensus understood by those of ordinary skill in the art (e.g., A, B, A and B together, A and C together, B and C together, and / or A, B and C together and so on Including but not limited to systems. In those instances where a similar convention is used, such as at least one of A, B, or C, etc., generally such a structure means a consensus understood by those of ordinary skill in the art (e.g., A, B, or C The system having at least one of A, B, C alone, A and B together, A and C together, B and C together, and / or A, B and C together But are not limited to). It will be apparent to those skilled in the art that the phrase "and / or" in practice, which provides for more than one alternative term in the description, the claims, or the drawings, Or < / RTI > terms used in connection with the present invention. For example, the phrase "A or B" should be understood to include the possibility of "A" or "B" or "A and B".

While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those of ordinary skill in the art. The various aspects and embodiments disclosed herein are for illustrative purposes only and not intended to be limiting, and the true scope and spirit of the invention is expressed by the following claims.

100: multi-plane mixing and separation system 101: base frame
102: motor 103: ball joint mechanism
104: Link 105: Fork
106: Cross bearing 107: Lower bars / pillars
107a: Cross links of lower pillars 108: Cross bearing cups
109: cross link 109a: connecting member
110: container holding frame 111: upper bar / pillars
112: MPMS vessel 112a: upper surface of MPMS vessel
112b: bottom surface of MPMS container 112c: inlet of MPMS container
112d: MPMS container outlet 113: linear bearing
114: Bush bearing 115: Link assembly
116: MPMS lift motor 117: projections
218: Controller 219: Chamber
220: Temperature sensor
221: Position sensor on ball joint mechanism
422: Position sensor on the container holding frame
423: Heating pad 500: SVF processing device
503: cell enrichment unit 505: user interface
506: buffer and enzyme container 507: heater
508: 3-way manifold 511: Pinch valve
512: metering pump 513: frame
514: waste storage tank 519: caster wheel

Claims (20)

A multi-planar mixer and separator (MPMS) system (100)
A base frame 101 of a predetermined shape configured to form a base of the MPMS system 100;
A motor 102 mounted to the base frame 101 for rotating the MPMS system 100;
Wherein one end of the ball joint mechanism (103) is fixed to the motor (102) using a link (104) and the other end of the ball joint mechanism (103) is coupled to the fork The ball joint mechanism;
A container holding frame (110) connected to a fork (105) using bars (111), said container holding frame (110) being slopeable upward by 120 degrees with respect to a base frame (101); And
Characterized in that it comprises an MPMS vessel of a predetermined shape which is removably mounted on a container holding frame (110) for mixing different density liquids. The method according to claim 1,
Wherein the fork (105) is a Y-shaped fork, and cross bearing cups (108) are fixed at the upper ends of the fork (105). The method according to claim 1,
A pair of bars 107 are mounted on the base frame 101 and at least one cross bearing cup 108 is fixed to the upper end of each bar using cross links 107a Flat mixer and separator system. The method according to claim 2 or 3,
Wherein the cross bearing (106) is wrapped around the cross bearing cup (108) to form a universal joint. The method according to claim 1,
And at least one position sensor (221) provided on the ball joint mechanism (103) for measuring the position of the ball joint mechanism (103)
Wherein the position sensor (221) is interfaced with a controller (218). The method according to claim 1,
A straight bearing 113 having a bush bearing 114 coupled to the container holding frame 110 using a link assembly 115 to tilt the container holding frame 110 upward by 120 degrees with respect to the base frame 101, And a separator system. The method according to claim 6,
Wherein the link assembly (115) comprises a pair of a first link and a second link that constitute a rotating treatment. The method according to claim 6,
And a motor (116) coupled to the linear bearing (113) to selectively raise and lower the MPMS vessel (112)
And the motor (116) is interfaced with the controller (218). The method according to claim 1,
And at least one position sensor (422) provided on the container holding frame (110) to control the elevation angle of the MPMS container,
And a position sensor (422) is interfaced with the controller (218). The method according to claim 1,
Wherein the motor (102) is interfaced with a controller (218), the speed and direction of rotation of the motor (102) being controlled by a controller (218). The method according to claim 1,
Wherein the MPMS vessel (112) comprises a curved top surface (112a) and a flat bottom surface (112b). 12. The method of claim 11,
The flat bottom surface 112b of the MPMS container 112 includes a plurality of projections 117 arranged in a predetermined pattern with a predetermined profile to enable homogeneous mixing without generating turbulence or shear forces Characterized by a multi-plane mixer and separator system. 13. The method of claim 12,
Wherein the shape of the protrusions (117) is at least one of a triangle, a square, a rectangle, a circle, an ellipse, and a baffle type. The method according to claim 1,
Wherein the MPMS vessel (112) comprises a semicircular inlet (112c) and a funnel-shaped outlet (112d). The method according to claim 1,
Wherein the MPMS vessel (112) is made aseptically. 15. The method of claim 14,
And at least one valve interfaced with the controller (218) to control the flow of liquids entering the MPMS vessel (112). The method according to claim 1,
Wherein the MPMS system (100) is embedded in a chamber (219). 18. The method of claim 17,
At least one temperature sensor (220) provided in the chamber (219) for measuring the temperature in the chamber (219)
Wherein the temperature sensor (220) is interfaced with a controller (218), and the controller is configured to maintain a temperature within the chamber (219) within a predetermined limit. The method according to claim 1,
Wherein the container holding frame (110) is rotated both clockwise and counterclockwise by a motor and a ball joint mechanism (103). The method according to claim 1,
Wherein the liquids are biological samples or non-biological samples, and the biological sample includes biological tissue, cells or other biological components.

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