Device for Cell Culturing and Processing
The present invention discloses a device for cell culturing and processing, applicable in the field of biological and genetic engineering experiments, which comprises at least one central distribution compartment, at least one incubation compartment; at least one processing compartment, a number of ducts to transfer fluids between said compartments, wherein a distribution cavity and a piston capable of moving back and forth in said distribution cavity for altering the operational volume of said distribution cavity are provided within said central distribution compartment, and a distribution valve controlling the connection between said distribution cavity and said ducts is provided at one end of said distribution cavity within the distribution compartment. During operation, cells grow and multiply in a cell suspension contained in the incubation compartment. The cell suspension may be transferred from said incubation compartment into one of the processing compartments by means of said central distribution valve and moving the piston within the distribution cavity. The present invention combines the central distribution compartments, the incubation compartments, and the processing compartments into a compact system, which replaces repetitive manual handling, saves time, avoids wasting raw experimental materials, reduces the risk of human exposure to hazardous materials, while accomplishing cell culturing and several types of cell processing experiments. The modular design and automatic operation allows running different types of experimental projects in a short amount of time, in particular experiments requiring multiple iterations.
The present invention describes a device used in the field of biological and genetic engineering, especially a device for cell cultivation, cell transformation and biological experiments.
BACKGROUND OF THE INVENTIONIn the field of microbiology, especially in the field of biological engineering and genetic engineering, researchers have to verify their theories, ideas and designs by means of experiments on cell cultures. These experiments often include but are not limited to the following steps:
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- 1. Cell cultivation, especially making the cells grow and multiply in a liquid nutrient medium;
- 2. Measuring the cell concentration in the liquid nutrient medium;
- 3. Separating the cells from the liquid nutrient medium;
- 4. Resuspending the cells with fresh liquid.
- 5. Transforming cells by means of chemical, electrical, or other physical means, and by introducing genetic material such as plasmids or oligonucleotides, etc.;
- 6. Sterilizing the instruments with alcohol or other agents;
- 7. Rinsing the instruments with water.
The current laboratory practice accomplishes the above steps through a sequence of manual operations on small batches of cells. The commonly used traditional experimental instruments include: test tube, shaker flask, shaking table, Petri dish, cuvette, syringe, pipette, centrifuge, membrane filter, and so on. When multiple rounds of experiments are required to achieve a desired result, considerable time and repetitive manual labor has to be invested in the process.
Of course, it is possible to combine conventional equipment into small plants and add control systems to achieve some degree of automation. The main drawback of this approach is that the different components are usually not meant to be combined and do not have matching specifications. The resulting bio-chemical plant will be too big and the required volume of cell culture will be too large for convenient use in a laboratory or with expensive materials.
SUMMARYIn order to solve the above problem, the present invention provides a compact, flexible and automated device for cell culturing and processing, which, may be used for different experimental projects, substitute repetitive manual handling, save time and labor, avoid wasting of raw materials, and minimize the risk of human exposure to potentially dangerous substances.
The technical solution for solving the above problem by the present invention is a device for cell culturing and processing, comprising at least one central distribution compartment, at least one incubation compartment; at least one processing compartment, a number of ducts to transfer fluids between said compartments, wherein a distribution cavity and a piston capable of moving back and forth in said distribution cavity for altering the operational volume of said distribution cavity are provided within said central distribution compartment, and a distribution valve controlling the connection between said distribution cavity and said ducts is provided at one end of said distribution cavity within the distribution compartment.
During operation, the cells grow and multiply in the incubation compartment. After connecting the incubation compartment to the distribution cavity by choosing a suitable position of the distribution valve in the central distribution compartment, liquid can be transferred between the compartments by moving the piston within the distribution cavity. Likewise, the distribution cavity can be connected to any of the processing compartments, which offer the possibility to accomplish tasks including removing cells from the nutrition medium and re-suspending them in another liquid, cooling, heating, optical density measurement, conductivity measurement, electro-transformation, and exposure to electro-magnetic radiation.
As a furthermore improvement of the technical solution of the present invention is that said central distribution compartments, said incubation compartments, said processing compartments are built as separate entities; furthermore, the distribution valve within the central distribution compartment comprises an essentially cylindrical valve cavity at one end of the distribution cavity and an essentially cylindrical valve core inserted into said valve cavity. The valve core is able to rotate within said valve cavity, and a multitude of flow channels which are provided in the valve core can establish different connections between said distribution cavity and any of the ducts leading to the distribution compartment's fitting surfaces by rotating the valve core.
As a furthermore improvement of the technical solution of the present invention we consider that at least one incubation compartment comprises an incubation cavity constructed by a cylindrical shell, a plug arranged at the top end of the shell, and a multiway valve arranged at the bottom end of said shell, said plug comprises an air hole, said multiway valve is fitted with at least two fitting surfaces and provided with an essentially cylindrical valve cavity, and ducts to connect the valve cavity to the fitting surfaces and the incubation cavity. An essentially cylindrical valve core is inserted into said valve cavity and able to rotate in the valve cavity. At least two flow channels are provided in said valve core, said flow channels being able to connect the first or second fitting surface to said incubation cavity or the two fitting surfaces when rotating the valve core in the valve cavity.
The design of the incubation compartment can be improved further if a sleeve is set at the outside of said shell, a cavity is formed between said sleeve and said shell, an exit and an entrance to said cavity are arranged at two opposite ends of said sleeve, a helical partition wall is provided in said cavity to form a helical channel surrounding said shell and connecting the exit and the entrance. The cavity between sleeve and shell can be used to control the incubators temperature by passing heating or cooling liquid through the cavity.
An alternative solution to provide heating/cooling capability to the incubator is to use a helical duct surrounding said shell, characterized in that the inner diameter of said helical duct is slightly less than the outer diameter of the incubation cavity when the helical duct is not mounted on the shell.
To add the ability to interact with cell suspension by means of electrical currents or voltages to the present invention, a processing compartment is provided with a duct and two electrodes. Those electrodes are arranged opposite to each other at both sides of the duct and electric couplers provided at the outer ends of said two electrodes can be used to connect an external power supply or a measurement amplifier. The electrodes can be separated by a non-conductive member for safety purposes and a flow guide can be grafted onto said member to guide the fluid flow between the electrodes.
To add the ability to separate cells from the medium and to re-suspend cells in fresh medium, a processing compartment comprises a main duct and filter unit dividing said main duct into a front segment and a back segment. Said filter unit comprises a filter membrane and a porous support arranged at the back side of said filter membrane. The body of the processing compartment comprises a front part and a rear part which may be assembled into a whole body. A cavity for the membrane and porous support is formed between said front part and said rear part. On the front side of the filter membrane, a helical fluid guide is grafted into the front half part and connected to a duct leading to a third fitting surface for injecting external fluid between said filtration membrane and said front half part.
Another possibility to provide filtration and re-suspension capability is to use a filter tube instead of a flat membrane. An appropriate processing compartment is provided with an elongated filtration cavity connected at one end to a fitting surface via a duct. A choke plug is tightly fitted into said processing compartment at the other end of said filtration cavity. The choke plug has an internal duct and a fitting surface. A membrane filter tube inserted into said filtration cavity is attached to the inner end of said choke plug in such a way, that the duct is connected to the inside of the membrane filter tube. An additional duct connects a fitting surface at the side wall of the processing compartment with the filtration cavity, and said additional duct merges with the filtration cavity in tangential direction.
To improve re-suspension of cells from the membrane filter tube, the inner wall of the filtration cavity can be provided with a helical fluid guide. On one end, the fluid guide is connected to said additional port and arranged surrounding the membrane filter tube.
To add the ability to measure cell concentration, a processing compartment is provided with a cavity and ducts that connect said cavity to two fitting surfaces. The processing compartment is provided with an optical pathway penetrating the cavity at an angle. The two ends of said optical pathway are formed by a light source and a light sensor respectively, said light source and light sensor are connected to the cavity by means of a transparent waveguide component.
Instead of using a separate entity for cell concentration measurement, the optical pathway can be placed at an angle to the distribution cavity in the central distribution compartment. This will reduce the number of steps required to measure cell concentration as the concentration can be measured as soon as the cell suspension enters the distribution cavity.
The benefit of the present invention is that a compact, flexible and automated assembly of different compartments offers to eliminate repetitive manual labor, shorten waiting and processing times, and reduce the possibility of human error and exposure to potentially harmful or dangerous agents. In addition the modular design allows to run different kinds of processes and to combine systems to run several experiments in parallel.
The present invention will be further described below with reference to the drawings.
Referring to the
Refer to the
As shown in
The flow channels 133 of the valve core 132 may have different shapes. For example, a flow channel 133 may penetrate through the valve core 132 or it may be located at the surface of the valve core 132. The valve core 132 shown in
Two elastic seal elements 136 are arranged at the two sides of the flow channels 133 on the valve core 132 to prevent fluid leakage along the long axis of the valve core 132.
The
When the valve core 132 rotates to position II, the distribution cavity 11 is connected to said processing compartment 3, while the ducts 14 thereabove and therebelow are closed off.
When the valve core 132 rotates to position III, the incubation compartment 2 and the processing compartment 3 are connected, while the distribution cavity 11 is connected to the duct 14 therebelow (e.g. to draw fluids from an external source into the distribution cavity 11). It should be noted that, in position III, in order to prevent the connection of the incubation compartment 2 and the processing compartment 3, the position may be changed by a few degrees from position III to position III′. Because the diameters of the distribution cavity 11 and the ducts 14 are different, the distribution cavity 11 may remain connected to the duct 14 therebelow, while keeping the other ducts 14 closed off.
When the valve core 132 rotates to position IV, all of the ducts 14 and the distribution cavity 11 are separated from each other; this position may be used for the standby mode of the equipment.
It is obvious to those skilled in the art that, the valve with slightly different characteristics can be obtained by varying the position, number, and length of the flow channels 133 and ducts 14 with respect to the distribution cavity 11.
In the present invention, the piston 12 is inserted into the distribution cavity 11 within the central distribution compartment 1 and may move axially in said distribution cavity 11. The piston 12 comprises of a rigid member 121 connected to a linear actuating device (not shown) and a flexible member 122 attached to the front end of said rigid member 121. This type of design is known from medical syringes and the syringe pump, and to use the design for the present invention possessed the following three advantages:
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- (i) The motion of piston 12 and its flexible member 122 along the walls of the distribution cavity 11 can keep the inner wall of said distribution cavity 11 clean. The self-cleaning function eliminates the need for additional cleaning steps and allows to use the same central distribution compartment 1 for different kinds of media;
- (ii) The motion of piston 12 and its flexible member 122 along the walls of the distribution cavity 11 can be used to draw and push liquids of different viscosity, solid-liquid suspensions (such as cell suspensions), and gases;
- (iii) By using the cross-sectional area of the distribution cavity 11, the linear motion of piston 12 can be easily used to calculate dispensed volumes or volumetric flow rates. If the driving force from the linear actuator is known, the system pressure can be calculated as well.
In addition, the central distribution valve 13 is located directly at one end of the distribution cavity 11, which reduces the residual fluid volume between the distribution cavity 11 and the distribution valve 13 to the minimum.
Refer to the
In one embodiment of the invention, a sleeve 25 is set at the outside of the shell 21, such that a cavity 26 is formed between the sleeve 25 and the shell 21. An exit 251 and entrance 252 are connected to the cavity 26 and arranged at two opposite ends of the sleeve 25. Cooling or heating fluid may be transported into the formed cavity 26 through the entrance 252 and returned to the heating/cooling system through the exit 251. In order to improve the heat conduction, a helical partition wall is provided in the cavity 26 to form a helical channel surrounding the shell 21 and connecting the exit 251 and the entrance 252 to guide the fluid flow (not shown).
Another embodiment of heating or cooling the culture cavity 23 is shown in the
In the following, several embodiments of possible processing compartments 3 are described, in particular, an electric processing compartment, two embodiments of a filtration compartment, and two embodiments of a cell density measurement compartment.
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- (i) Fresh fluid may be introduced through the rear part 325 and pressed through the filter membrane 322 from the back side of the filter membrane 322;
- (ii) Fresh fluid may be injected into the front part 324 through the port 327 and the helical flow guide 326 which causes the fresh fluid to flow over the cells deposited on the filter membrane 322.
While cells are being deposited on the filtration membrane 322 at the beginning of the process, port 327 is closed off, preferably by connecting a standard shape block with a valve to the fitting surface around port 327. This makes sure that cell suspension will not escape through port 327, but will be passed through the filter membrane 322 as described above.
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- (1) Fresh fluid may be introduced through the duct 4 in the choke plug 333 and pressed to penetrate reversely through the tubular filtration membrane 334;
- (2) Fresh fluid may enter into the filtration cavity 332 from the port 335, to generate a helical flow pattern around the tubular filtration membrane 334 which will lift the deposited cells off the surface of the tubular filtration membrane 334.
Refer to the
As shown in the
In order to allow experimenters to arrange the compartments freely according to their experimental design, the present invention adopts the idea of a “standard shape block” as the basis of all compartments.
The
Refer to the
In order to ensure good alignment of two adjacent compartments, compartments can be equipped with matching holes 43 in the fitting surface in such a way that alignment by means of the simple connector element 44 can be guaranteed, wherein the connector element 44 may be a simple cylindrical pin or a flat key.
Certainly, the present invention is not limited to the above embodiments, the skilled person in the field may think of equivalent modifications or alternatives in the premise of not prejudice to the which are also in agreement with the spirit of the present invention, and these equivalent modifications or alternatives are all be comprised in the scope defined by the claims of this application.
Claims
1. A device for cell culturing and processing, which comprises at least one central distribution compartment, at least one incubation compartment; at least one processing compartment, a number of ducts to transfer fluids between said compartments, wherein a distribution cavity and a piston capable of moving back and forth in said distribution cavity for altering the operational volume of said distribution cavity are provided within said central distribution compartment, and a distribution valve controlling the connection between said distribution cavity and said ducts is provided at one end of said distribution cavity within the distribution compartment.
2. The device for cell culturing and processing of claim 1, characterized in that, said central distribution compartments, said incubation compartments, said processing compartments are built as separate entities, in such a way that each entity's body is equivalent to one or more standard shape blocks, ducts in said entities are connected to a number of fitting surfaces on said entities, said entities can be joined together at the fitting surfaces to connect the ducts in said entities, said distribution valve within the distribution compartment comprises an essentially cylindrical valve cavity at one end of the distribution cavity and an essentially cylindrical valve core inserted into said valve cavity, where the valve core is able to rotate within said valve cavity, and a multitude of flow channels provided in the valve core can establish different connections between said distribution cavity and any of the ducts leading to the distribution compartment's fitting surfaces by rotating the valve core.
3. The device for cell culturing and processing of claim 2, characterized in that at least one incubation compartment comprises an incubation cavity constructed by a cylindrical shell, a plug arranged at the top end of the shell, and a multiway valve arranged at the bottom end of said shell, said plug comprises an air hole, said multiway valve is fitted in a body the volume of which is equivalent to one or more standard shape blocks and said body having at least two fitting surfaces and provided with an essentially cylindrical valve cavity, ducts to connect said valve cavity to the fitting surfaces and the incubation cavity, an essentially cylindrical valve core inserted into said valve cavity and able to rotate in the valve cavity, at least two flow channels are provided in said valve core, said flow channels being able to connect the first fitting surface to said incubation cavity, to connect the second fitting surface to the said incubation cavity, or to connect the two fitting surfaces when rotating the valve core in the valve cavity.
4. The device for cell culturing and processing of claim 3, characterized in that, a sleeve is set at the outside of said shell, a cavity is formed between said sleeve and said shell, an exit and an entrance to said cavity are arranged at two opposite ends of said sleeve, a helical partition wall is provided in said cavity to form a helical channel surrounding said shell and connecting the exit and the entrance.
5. The device for cell culturing and processing of claim 3, characterized in that, a helical duct is provided surrounding said shell, characterized in that the inner diameter of said helical duct is slightly less than the outer diameter of the incubation cavity when the helical duct is not mounted on the shell, and that the tension created by expanding the helical duct when fitting it on said shell will provide intimate contact between said helical duct and said shell.
6. The device for cell culturing and processing of claim 2, characterized in that one of said processing units is housed in a body the volume of which is equivalent to one or more standard shape blocks, said body is provided with two ducts which connect two fitting surfaces to a central cavity, characterized in that two electrodes are arranged opposite to each other at each sides of said cavity, electric connectors are provided to connect an external power supply or an electrical measurement amplifier at the outer ends of said two electrodes, an insulation member is arranged inside the cavity between the two electrodes, and a flow channel is formed on said insulation member to guide the liquid flow through said cavity between said two electrodes.
7. The device for cell culturing and processing of claim 2, characterized in that, one of said processing compartments is housed in a body the volume of which is equivalent to one or more standard shape blocks, said body is provided with a main duct connected to two of the body's fitting surfaces, and a filter unit dividing the main duct into a front segment and a back segment, said filter unit comprises a filter membrane and a porous support arranged at the back side of said filter membrane, said body comprises a front part and a rear part which may be assembled into a whole body, a cavity for the membrane and porous support is formed between said front part and said rear part, a helical fluid guide is provided in close proximity to said filter membrane in said front part, said helical flow guide is connected to a side duct leading to a third fitting surface for injecting external fluid between said filtration membrane and said front part.
8. The device for cell culturing and processing of claim 2, characterized in that, one of said processing compartments is housed in a body the volume of which is equivalent to one or more standard shape blocks, in its interior said body is provided with a filtration cavity extending essentially along the long axis of said body, one end of said filtration cavity is connected to a fitting surface by means of a duct, a choke plug is tightly fitted into said processing compartment at the other end of said filtration cavity and provided with an internal duct and a fitting surface, a membrane filter tube inserted into said filtration cavity is attached to the inner end of said choke plug so that said internal duct connects the inside of the filter tube to said fitting surface of said choke plug, and an additional duct connects the filtration cavity with a third fitting surface at the side wall of the processing compartment, and said additional duct merges with the filtration cavity in tangential direction.
9. The device for cell culturing and processing of claim 8, characterized in that, the inner wall of the filtration cavity is provided with a helical fluid guide, which is connected to said additional duct and third fitting surface and arranged surrounding the membrane filter tube inside the filtration cavity.
10. The device for cell culturing and processing of claim 2, characterized in that one of said processing units is housed in a body the volume of which is equivalent to one or more standard shape blocks, said body is provided with ducts which connect two fitting surfaces to a cavity, an optical pathway penetrating the cavity at an angle, the two ends of said optical pathway are formed by a light source and a light sensor respectively, light source and light sensor are connected to the cavity by means of a transparent waveguide component.
11. The device for cell culturing and processing of claim 1, characterized in that, said central distribution compartment is provided with an optical pathway penetrating the distribution cavity at an angle, the two ends of said optical pathway are formed by a light source and a light sensor respectively, light source and light sensor are connected to the distribution cavity by means of a transparent waveguide component.
Type: Application
Filed: Apr 11, 2014
Publication Date: May 11, 2017
Inventors: Jinming Cui (Guangzhou City, Guangdong), Shijie Zeng (Guangzhou City, Guangdong), Olaf Eichstaedt (Guangzhou City, Guangdong), Jiandong Huang (Guangzhou City, Guangdong), Ruxu Du (Guangzhou City, Guangdong)
Application Number: 14/434,661