CN101717720B - Micro-fluidic cell culture unit - Google Patents
Micro-fluidic cell culture unit Download PDFInfo
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- CN101717720B CN101717720B CN2009102438166A CN200910243816A CN101717720B CN 101717720 B CN101717720 B CN 101717720B CN 2009102438166 A CN2009102438166 A CN 2009102438166A CN 200910243816 A CN200910243816 A CN 200910243816A CN 101717720 B CN101717720 B CN 101717720B
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Abstract
The invention relates to a micro-fluidic cell culture unit which mainly comprises a cell culture section, two liquid transitional sections and two liquid transmission sections, wherein the cell culture section is positioned at the center of the cell culture unit and is provided with an inlet and an outlet which are used for transmitting cells; the liquid transitional section is positioned at the periphery of the cell culture section and is used for connecting the cell culture section and the liquid transmission section; and the liquid transmission section is provided with an inlet and an outlet which are used for transmitting cell culture liquid and reagents for indicating cells. Owing to the special shape of the liquid transmission section, the cell culture unit enables the flow field distribution in the cell culture section to be evener. The invention has the advantages of being beneficial to the even diffusion for the reagent and the even transmission of the cell culture liquid, and effectively reducing the influence of the shearing force on cells on the premise of ensuring the required nutritional ingredient of the cells.
Description
Technical field
The invention belongs to micro-current controlled cell and cultivate chip field, particularly relate to a kind of micro-fluidic cell culture unit.
Background technology
All need carry out cell cultures in every field such as virusology, immunology, genetics, oncology, but there is obviously deficiency in conventional cell culture processes.The volume that at first is cell is small, the culture environment that traditional method provides obviously and internal milieu differ greatly, be difficult to the true environment of comprehensive simulated cell life; Be exactly that the cell desired number is huge in addition, be difficult for carrying out single celled control and manipulation, observe not directly, expend reagent.With micro-fluidic chip and the cell culture technology resulting cell cultivation chip that combines, has obvious superiority.Say that from device size chip size characteristic and single biomass cells have consistency on yardstick, help to realize single celled Biochemistry Experiment; On structure, interior mass transfer of chip and thermal conduction are very fast, help the fast and stable of cell culture environment; Say from integration, can integrated multiple parts and function on the chip, be prone to realize the microminiaturization of cell culture apparatus.Because the existence of these advantages, cell cultivation chip plays an increasingly important role in a plurality of fields such as cell migration, cytodifferentiation, drug screenings.
The reagent of indicator cells and the perfusion of cell culture fluid are the key factors that influences the cell cultures success or not, also are the difficult points of cell cultivation chip design.When the reagent flow velocity that pours into indicator cells was big, caused shearing force can have a negative impact by pair cell; When flow velocity was too small, reagent just can not spread uniformly, thus the result that influence detects.When perfusion cell cultures flow velocity is big, the waste cell culture fluid, and also the shearing force that big flow velocity causes can have a negative impact by pair cell; When flow velocity is too small, possibly causes nutrition and the accumulation of supporting not enough and poisonous secretory product, thereby influence the normal growth of cell.Therefore, for realizing the stable cultivation of cell, not only need select a suitable flow velocity to pour into the reagent and the cell culture fluid of indicator cells, and need to guarantee the even transmission of liquid in the cell cultures district.
At present, the document that does not also have patent or other to publish can well address the above problem.Has only a small amount of document; Article paper one " A novel high aspect ratiomicrofluidic design to provide a stable and uniform microenvironment for cellgrowth in a high throughput mammalian cell culture array " (the Lab Chip that on Lab Chip, publishes like people such as P.J.Hung; 2005; Vol.5; The disadvantageous effect that pair cell caused when the construction design method that 44-48) provides can reduce perfusion culture liquid, but have the inhomogeneous and baroque problem of flow velocity.As shown in Figure 1, this micro-fluidic cell culture unit includes the cell cultures cavity of a circle, and one group around the perfusion channel that is spacedly distributed around the main cavity, and four mouths that are used for the fluid transmission.The reagent of cell suspending liquid and indicator cells is from injection suitable for reading, and end opening is discharged; Cell culture fluid is mouthful injection from a left side, discharges for right mouthful.The Chinese implication of figure Chinese and English is: Cell Loading (cell loading), Perfusion Inlet (perfusion inlet), Cell Culture Chamber (cell culture chamber), Perfusion Outlet (perfusion outlet).
Summary of the invention
Technology of the present invention is dealt with problems and is: be the disadvantageous effect problem of the pair cell that perfusion produced of the reagent that solves above-mentioned indicator cells and cell culture fluid; A kind of micro-fluidic cell culture unit that can under the reagent of a certain amount of indicator cells and the dabbling situation of cell culture fluid, effectively reduce the disadvantageous effect of corresponding pair cell is provided; The even transmission that is intended to realize pair cell nutrient solution and cell detection reagent is eliminated or the disadvantageous effect problem of pair cell when weakening reagent and the cell cultures perfusion of indicator cells simultaneously, realizes the stable cultivation of pair cell.
Technical solution of the present invention: a kind of micro-fluidic cell culture unit; Has oval-shaped groove; Major axis and short-axis direction at oval-shaped groove have four grooves that are communicated with oval-shaped groove respectively; The degree of depth of these four grooves is identical with the degree of depth of oval-shaped groove, and wherein first groove of short-axis direction and the 3rd groove are used separately as the entrance and exit in cell cultures district, are used for transfusion cell; Second groove of long axis direction and the 4th groove are used separately as the entrance and exit of liquid transmission section, are used for the reagent of transfusion cell nutrient solution and indicator cells; Have the annulus wall in the oval-shaped groove bottom surface, this annulus wall is provided with elliptical slot is concentric, and its diameter highly is slightly less than the degree of depth of oval-shaped groove less than the length of oval-shaped groove short-axis direction; Said annulus wall forms the 5th groove and the 6th groove in the position relative with the 3rd groove with first groove; Thereby this annulus wall is divided into symmetric first arcwall and second arcwall; Outer side in the opposite end of two arcwalls has parallel connecting wall respectively, is used to connect arcwall and oblong fovea cell wall; The 5th groove and first groove and the 6th groove and the 3rd groove are communicated with, thereby form the entrance and exit in cell cultures district; In elliptical wall and adjacent arcwall and the part between the connecting wall is liquid transmission section, is used to make the flow velocity of reagent of cell culture fluid and indicator cells more even; Zone between two arcwalls is the cell cultures district, is used to install nutrient solution and treats cultured cells; The zone of two arcwalls and connecting wall top is used to connect liquid transmission section and cell cultures district as the fluid transition district.
The described liquid transmission section degree of depth is identical with the cell cultures district; The arcwall of below, described fluid transition district and the height of connecting wall are identical, and are slightly less than the degree of depth of oval-shaped groove.
Principle of the present invention: traditional method generally is that the direct perfusion of the reagent of indicator cells is advanced in the cell cultures district, and is even in order to make diffusion of reagents, can only take big flow velocity, will produce adverse influence by pair cell.Therefore, the present invention is conceived to the approach of reagent transmission, starts with from the shape that changes the cell culture fluid transmission range, proposes such scheme.Through the special shape of design cell culture fluid transmission range, after reagent or cell culture fluid entered into the cell culture fluid transmission range from inlet, its Flow Field Distribution was more even, thereby made the Flow Field Distribution in the cell cultures district also become more even; Effectively isolate nutrient solution transmission range and cell cultures district through the cell culture fluid zone of transition, cell is avoided streamed direct influence, thereby eliminated or weakened the disadvantageous effect of reagent or the generation of cell cultures perfusion pair cell.
The present invention's beneficial effect compared with prior art is: because the special shape of cell culture fluid transmission range makes the Flow Field Distribution in the cell cultures district more even; The one, help the even diffusion of reagent; The 2nd, help the even transmission of cell culture fluid, the 3rd, more help the influence that more effectively reduces reagent or cell cultures perfusion pair cell under the prerequisite of normally carrying out with cell desired nutritional composition guarantee detecting.
Description of drawings
Fig. 1 is the structural representation of a kind of micro-fluidic cell culture unit of the prior art;
Fig. 2 is the structural representation of the micro-fluidic cell culture unit of the present invention's proposition;
Fig. 3 is the front view of the micro-fluidic cell culture unit of the present invention's proposition;
Fig. 4 is the emulation synoptic diagram of velocity flow profile in a kind of micro-fluidic cell culture unit of the prior art;
Fig. 5 is the emulation synoptic diagram of velocity flow profile in the micro-fluidic cell culture unit of the present invention's proposition.
Embodiment is
As shown in Figure 2; Micro-fluidic cell culture unit of the present invention has oval-shaped groove; Major axis and short-axis direction at oval-shaped groove have four grooves that are communicated with oval-shaped groove respectively; The degree of depth of these four grooves is identical with the degree of depth of oval-shaped groove, and wherein first groove 1 of short-axis direction and the 3rd groove 2 are used separately as the entrance and exit in cell cultures district, are used for transfusion cell; Second groove 3 of long axis direction and the 4th groove 4 are used separately as the entrance and exit of liquid transmission section, are used for the reagent of transfusion cell nutrient solution and indicator cells; Have the annulus wall in the oval-shaped groove bottom surface, this annulus wall is provided with elliptical slot is concentric, and its diameter highly is slightly less than the degree of depth of oval-shaped groove less than the length of oval-shaped groove short-axis direction; Said annulus wall is forming the 5th groove 5 and the 6th groove 6 with first groove 1 and the 3rd groove 2 relative positions; Thereby this annulus wall is divided into symmetric first arcwall and second arcwall; Outer side in the opposite end of two arcwalls has parallel connecting wall respectively, is used to connect arcwall and oblong fovea cell wall; The 5th groove 5 and first groove 1 and the 6th groove 6 and the 3rd groove 2 are communicated with, thereby form the entrance and exit in cell cultures district; In elliptical wall and adjacent arcwall and the part between the connecting wall is liquid transmission section 7, is used to make the flow velocity of reagent of cell culture fluid and indicator cells more even; Zone between two arcwalls is cell cultures district 8, is used to install nutrient solution and treats cultured cells; The zone of two arcwalls and connecting wall top is used to connect liquid transmission section 7 and cell cultures district 8 as fluid transition district 9.
As shown in Figure 3, liquid transmission section 7 degree of depth are identical with cell cultures district 8; The arcwall of 9 belows, fluid transition district and the height of connecting wall are identical, and are slightly less than the degree of depth of oval-shaped groove.
As shown in Figure 5; Dark representative is than minimum velocity, and the big flow velocity of light color representative is compared with the velocity flow profile (as shown in Figure 4) in a kind of micro-fluidic chip of the prior art; Flow Field Distribution of the present invention is more even, more helps the even diffusion of cell culture fluid and reagent.
Embodiments of the invention more than have been described, but the present invention do not limit to and above-described specific embodiment, every various micro-current controlled cells that meet purport of the present invention are cultivated chips, all should think within the scope of the present invention.
Claims (3)
1. micro-fluidic cell culture unit; It is characterized in that: said micro-fluidic cell culture unit has oval-shaped groove; Major axis and short-axis direction at oval-shaped groove have four grooves that are communicated with oval-shaped groove respectively; The degree of depth of said four grooves is identical with the degree of depth of oval-shaped groove, and wherein first groove (1) of short-axis direction and the 3rd groove (2) are used separately as the entrance and exit in cell cultures district, are used for transfusion cell; Second groove (3) of long axis direction and the 4th groove (4) are used separately as the entrance and exit of liquid transmission section, are used for the reagent of transfusion cell nutrient solution and indicator cells; Have the annulus wall in the oval-shaped groove bottom surface, said annulus wall is provided with elliptical slot is concentric, and its diameter highly is slightly less than the degree of depth of oval-shaped groove less than the length of oval-shaped groove short-axis direction; Said annulus wall is forming the 5th groove (5) and the 6th groove (6) with first groove (1) and the relative position of the 3rd groove (2); Thereby said annulus wall is divided into symmetric first arcwall and second arcwall; Outer side in the opposite end of two arcwalls has parallel connecting wall respectively, is used to connect arcwall and oblong fovea cell wall; The 5th groove (5) and first groove (1) and the 6th groove (6) and the 3rd groove (2) are communicated with, thereby form the entrance and exit in cell cultures district; In elliptical wall and adjacent arcwall and the part between the connecting wall is liquid transmission section (7), is used to make the flow velocity of reagent of cell culture fluid and indicator cells more even; Zone between two arcwalls is cell cultures district (8), is used to install nutrient solution and treats cultured cells; The zone of two arcwalls and connecting wall top is used to connect liquid transmission section (7) and cell cultures district (8) as fluid transition district (9).
2. micro-fluidic cell culture unit according to claim 1 is characterized in that: described liquid transmission section (7) degree of depth is identical with cell cultures district (8).
3. micro-fluidic cell culture unit according to claim 1 is characterized in that: the arcwall of below, described fluid transition district (9) and the height of connecting wall are identical, and are slightly less than the degree of depth of oval-shaped groove.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009102438166A CN101717720B (en) | 2009-12-22 | 2009-12-22 | Micro-fluidic cell culture unit |
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| CN2009102438166A CN101717720B (en) | 2009-12-22 | 2009-12-22 | Micro-fluidic cell culture unit |
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| CN101717720B true CN101717720B (en) | 2012-05-16 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286373B (en) * | 2011-08-01 | 2013-12-11 | 北京航空航天大学 | Microfluidic cell culture unit with variable structure |
| CN106318869B (en) * | 2016-11-27 | 2018-06-26 | 重庆科技学院 | A kind of cell flow experiment biochip |
| CN106434347B (en) * | 2016-11-27 | 2018-10-23 | 重庆科技学院 | A kind of cell culture biochip for shearing force experiment |
| CN106544272B (en) * | 2016-11-27 | 2019-07-23 | 重庆科技学院 | A kind of application method of the biochip for shearing force experiment |
| CN106701573B (en) * | 2016-11-27 | 2018-10-23 | 重庆科技学院 | A kind of cell flow experiment biochip application method |
| WO2019121984A1 (en) * | 2017-12-20 | 2019-06-27 | Philip Morris Products S.A. | Improved cell culture device |
| US20230313106A1 (en) * | 2020-04-30 | 2023-10-05 | Xingyue Peng | Method for constructing slow microcyclic artificial cell niche and apparatus thereof |
| CN112481077B (en) * | 2020-12-01 | 2022-11-08 | 北京理工大学 | Microfluidic perfusion culture device and perfusion method thereof |
Citations (5)
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| CN101165161A (en) * | 2007-07-27 | 2008-04-23 | 中国科学院上海微系统与信息技术研究所 | Micro-fluid concentration gradient cell culture chip and its preparation method and application |
| CN101270333A (en) * | 2008-05-05 | 2008-09-24 | 深圳先进技术研究院 | Micro-current controlled cell chip |
| CN101285036A (en) * | 2008-05-16 | 2008-10-15 | 深圳先进技术研究院 | Automatic cell culture microflow control chip device and method thereof |
| US20090081773A1 (en) * | 2007-09-25 | 2009-03-26 | Cytyc Corporation | Microfluidic apparatus for manipulating imaging and analyzing cells of a cytological specimen |
| CN101550396A (en) * | 2009-05-08 | 2009-10-07 | 深圳先进技术研究院 | High-throughput microfluidic cell chip |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101165161A (en) * | 2007-07-27 | 2008-04-23 | 中国科学院上海微系统与信息技术研究所 | Micro-fluid concentration gradient cell culture chip and its preparation method and application |
| US20090081773A1 (en) * | 2007-09-25 | 2009-03-26 | Cytyc Corporation | Microfluidic apparatus for manipulating imaging and analyzing cells of a cytological specimen |
| CN101270333A (en) * | 2008-05-05 | 2008-09-24 | 深圳先进技术研究院 | Micro-current controlled cell chip |
| CN101285036A (en) * | 2008-05-16 | 2008-10-15 | 深圳先进技术研究院 | Automatic cell culture microflow control chip device and method thereof |
| CN101550396A (en) * | 2009-05-08 | 2009-10-07 | 深圳先进技术研究院 | High-throughput microfluidic cell chip |
Non-Patent Citations (2)
| Title |
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| Paul J. Hung等.A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array.《Lab Chip》.2004,第5卷44-48. * |
| 李晓宇等.微流控技术在细胞生物学中的应用.《生命科学》.2008,第20卷(第3期),397-401. * |
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