CN101705179A - Tumor cell drug resistance detecting chip - Google Patents
Tumor cell drug resistance detecting chip Download PDFInfo
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- CN101705179A CN101705179A CN200910258600A CN200910258600A CN101705179A CN 101705179 A CN101705179 A CN 101705179A CN 200910258600 A CN200910258600 A CN 200910258600A CN 200910258600 A CN200910258600 A CN 200910258600A CN 101705179 A CN101705179 A CN 101705179A
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Abstract
The invention discloses a tumor cell drug resistance detecting chip, which comprises a chip body. The surface of the chip body is provided with a medicament inlet, a culture solution inlet and a cell inlet; a medicament passage and a culture solution passage are arranged in the chip body; a radial aggregation passage is arranged at a position where the medicament passage and the culture solution passage meet; the radial end of the aggregation passage is communicated with a plurality of pipelines; each pipeline is separated into small pipes; a cell pool is arranged on each small pipe; the other end of each pipeline and the other end of each small pipe are connected with a cell inlet passage which is communicated with the cell inlet; the lower part of the cell pool is provided with a pH indicating layer; a carbon dioxide permeable membrane is arranged between the cell pool and the pH indicating layer; and an acid-base indicator is placed in the pH indicating layer. The tumor cell drug resistance detecting chip has a simple structure and can simulate blood capillaries in vivo and complete multi-parameter analysis related to a multiple drug resistance mechanism.
Description
Technical field
The present invention relates to a kind of drug resistance detecting chip, particularly a kind of drug resistance detecting chip at tumour cell.
Background technology
In recent years, China's tumor incidence and mortality ratio are in rising trend always.Chemotherapy is the main means of current treatment malignant tumour, and the life-time service of traditional chemotherapeutics makes the drug resistance of tumor cell phenomenon more and more general, and has become and cause the modal and the most formidable problem of clinical tumor chemotherapy failure.Wherein, many resistances are principal modes of drug resistance of tumor cell, refer to a kind of drug effect after tumour cell makes it to produce resistance, this tumour cell also has cross resistance to not contacted, structure-irrelevant, action target spot and the different multiple antitumor drug of mechanism gradually.Therefore, have crucial meaning for people to antitumor for the detection of tumor cell drug resistance.Studies show that, low pH and its resistance of the outer microenvironment of tumour cell are in close relations, people utilize this characteristic to set about detecting the resistance of tumour cell, as the test of short-term primary cultured cell poison, mainly comprise tetrazole (MTT) colorimetry, XTT (MTT analogue) colorimetry, ATP-TCA methods such as (ATPtumor chemosensitivity assay).But there is the following problem in these conventional tumor drug resistance detection meanss:
(1), can not the detection of dynamic tumour cell and the interaction process of medicine, as the variation of the outer microenvironment pH of tumour cell;
(2), the experiment medicine can not form successive drug level gradient automatically, difficult active drug concentration is carried out preferably;
(3), in the residing microenvironment of tumor cell culture and the body at a distance of very big, as virose metabolite can not in time be eliminated, the residing space of relative body inner cell, cell space of living in is much bigger;
(4), can not study multiple resistance mechanism simultaneously, as the proton pump function of tumour cell, efflux pump function (P glycoprotein pumping function, P-gp), the detection etc. of reductive glutathione in the born of the same parents.
Summary of the invention
In order to solve the above problems, the object of the present invention is to provide a kind of can analogue body in the capillary blood vessel environment, the nutrition supply in the assurance cell cultivation process and the removing of metabolite, automatically it is poor to form drug level, but potential of hydrogen changing conditions around the detection of dynamic tumour cell, the effectively chip that the relevant multiparametric analysis of drug resistance of tumor cell mechanism is detected.
The present invention solves the technical scheme that its problem adopts:
A kind of tumor cell drug resistance detecting chip, comprise the chip body, described chip body one end surfaces is provided with medicine inlet and nutrient solution inlet, the other end surface is provided with the cell inlet, be provided with end in the described chip body and meet at together drug channel and nutrient solution passage, the described drug channel the other end communicates with the medicine inlet, the nutrient solution passage the other end communicates with the nutrient solution inlet, described drug channel and nutrient solution passage intersection are provided with polymerization passage radially, be communicated with many pipelines on the described polymerization passage spoke side, told tubule on the described pipeline, described tubule is provided with cell pool, described pipeline, the tubule the other end connects the cell access road, and described cell access road communicates with the cell inlet; Described cell pool bottom is provided with the pH marker, is provided with the penetrating film of carbonic acid gas between described cell pool and the pH marker, is placed with acid base indicator in the described pH marker.
As improvement of the technical scheme, also be provided with a control group on the described chip body, comprise the control group nutrient solution inlet that is arranged on the chip body surface, the connection of described control group nutrient solution inlet is arranged on the intrinsic control group nutrient solution of chip passage, told the control group tubule on the described control group nutrient solution passage, described control group tubule is provided with the cellular control unit pond, described contrast culture liquid passage, the control group tubule the other end connects the cellular control unit access road, described cellular control unit access road communicates with the cellular control unit inlet, bottom, described cellular control unit pond is provided with control group pH marker, be provided with the penetrating film of control group carbonic acid gas between described cellular control unit pond and the control group pH marker, be placed with acid base indicator in the described control group pH marker.
As further improvement in the technical proposal, described chip body comprises glass substrate and is positioned at the silica gel chip on glass substrate top that described pH marker is positioned on the glass substrate.
As further improvement in the technical proposal, the cell pool on the described tubule has two at least.
As further improvement in the technical proposal, described tubule is provided with many.
As further improvement in the technical proposal, described control group tubule is provided with many.
As further improvement in the technical proposal, the cellular control unit pond on the described control group tubule has two at least.
The invention has the beneficial effects as follows: tumor cell drug resistance detecting chip of the present invention is simple in structure, can imitate intravital capillary blood vessel, guarantee that nutrition is continuously altogether to constantly removing with metabolite in the cell cultivation process, utilize that two kinds of different liquid can form laminar flow in the chip microchannel, infiltration forms the successive concentration gradient, it is preferred to finish active drug concentration, and be integrated with the pH marker in cell pool bottom, potential of hydrogen changing conditions around can the detection of dynamic tumour cell obtains the relation between the outer microenvironment acidifying of tumour cell and the resistance generation; The parallel connection of many interior microchannels of chip repeats to be provided with, and can finish the relevant multiparametric analysis of multidrug resistant mechanism.
Description of drawings
The invention will be further described below in conjunction with drawings and Examples:
Fig. 1 is a structural representation of the present invention;
Fig. 2 is a cell pool structural representation of the present invention;
Fig. 3 is a cellular control unit pool structure synoptic diagram of the present invention;
Fig. 4 is a chip cross sectional representation of the present invention.
Embodiment
Referring to figs. 1 through Fig. 4, a kind of tumor cell drug resistance detecting chip of the present invention, comprise chip body 1, described chip body 1 one end surfaces are provided with medicine inlet 11 and nutrient solution inlet 12, the other end surface is provided with cell inlet 13, be provided with end in the described chip body 1 and meet at together drug channel 13 and nutrient solution passage 14, described drug channel 13 the other ends communicate with medicine inlet 11, nutrient solution passage 14 the other ends communicate with nutrient solution inlet 12, described drug channel 13 and nutrient solution passage 14 intersections are provided with polymerization passage 15 radially, be communicated with many pipelines 16 on described polymerization passage 15 spoke sides, told tubule 17 on the described pipeline 16, described tubule 17 is provided with cell pool 18, described pipeline 16, tubule 17 the other ends connect cell access road 19, and described cell access road 19 communicates with cell inlet 13; Described cell pool 18 bottoms are provided with pH marker 20, be provided with the penetrating film 4 of carbonic acid gas between described cell pool 18 and the pH marker 20, being placed with acid base indicator in the described pH marker 20. tumor cell drug resistance detecting chip of the present invention is simple in structure, can imitate intravital capillary blood vessel, continuous supply of nutrition and metabolite are constantly removed in the assurance cell cultivation process, utilize that two kinds of different liquid can form laminar flow in the chip microchannel, infiltration forms the successive concentration gradient, it is preferred to finish active drug concentration, and be integrated with the pH marker in cell pool bottom, potential of hydrogen changing conditions around can the detection of dynamic tumour cell obtains the relation between the outer microenvironment acidifying of tumour cell and the resistance generation; The parallel connection of many interior microchannels of chip repeats to be provided with, can finish the relevant multiparametric analysis of multidrug resistant mechanism. the present invention in use can join tumor cell line cell 13 places that enter the mouth earlier, gently cell is filled in each cell pool at medicine 11 places that enter the mouth with little negative pressure pump, insert medicine bottle, culture jar etc. at medicine inlet 11 and vehicle 12 places that enter the mouth again. at this moment, cell inlet 13 can be used as Waste outlet, with the suction of little negative pressure pump, make soup, nutrient solution enter in the pipeline of chip and carry out culture experiment.
In addition, as preferred implementation, also be provided with a control group on the described chip body 1, comprise the control group nutrient solution inlet 21 that is arranged on chip body 1 surface, described control group nutrient solution inlet 21 is communicated with the control group nutrient solution passage 22 that is arranged in the chip body 1, told control group tubule 23 on the described control group nutrient solution passage 22, described control group tubule 23 is provided with cellular control unit pond 24, described contrast culture liquid passage 22, control group tubule 23 the other ends connect cellular control unit access road 25, described cellular control unit access road 25 communicates with cellular control unit inlet 26,24 bottoms, described cellular control unit pond are provided with control group pH marker 27, be provided with the penetrating film 5 of control group carbonic acid gas between described cellular control unit pond 24 and the control group pH marker 27, be placed with acid base indicator in the described control group pH marker 27.Because the control group that is provided with is obstructed, does not have drug effect, can contrast intuitively with the test group of logical medicine, help analysis and research.
Described chip body 1 comprises glass substrate 2 and is positioned at the silica gel chip 2 on glass substrate 2 tops that described pH marker 20 and control group pH marker 27 are positioned on the glass substrate 2.Chip bottom adopts glass substrate 2, can observe directly pH indicator discoloration situation, comparatively intuitively obtains the result.
As preferably, described tubule 17 is provided with at least two each and every one cell pools 17, and described tubule 17 is provided with many, and described control group tubule 23 also is provided with many, and control group tubule 23 is provided with at least two cellular control unit ponds 24.In the present embodiment, tubule 17 is provided with two groups because tubule 17 is to tell the both sides that are arranged on pipeline 16, can parody in tiny blood vessels and microvascular mode of connection, simulated in vivo environment is for test provides reliable assurance.And every tubule 17 and control group tubule 23 are provided with three cell pools, like this, can satisfy clinical requirement, and repeatability detects preferably.
Certainly, the invention is not limited to above-mentioned embodiment, those of ordinary skill in the art also can make all equivalent variations or replacement under the prerequisite of spirit of the present invention, modification that these are equal to or replacement all are included in the application's claim institute restricted portion.
Claims (7)
1. tumor cell drug resistance detecting chip, it is characterized in that: comprise chip body (1), described chip body (1) one end surfaces is provided with medicine inlet (11) and nutrient solution inlet (12), the other end surface is provided with cell inlet (13), be provided with end in the described chip body (1) and meet at together drug channel (13) and nutrient solution passage (14), described drug channel (13) the other end communicates with medicine inlet (11), nutrient solution passage (14) the other end communicates with nutrient solution inlet (12), described drug channel (13) and nutrient solution passage (14) intersection are provided with polymerization passage (15) radially, be communicated with many pipelines (16) on described polymerization passage (15) spoke side, told tubule (17) on the described pipeline (16), described tubule (17) is provided with cell pool (18), described pipeline (16), tubule (17) the other end connects cell access road (19), and described cell access road (19) communicates with cell inlet (13); Described cell pool (18) bottom is provided with pH marker (20), is provided with the penetrating film of carbonic acid gas (4) between described cell pool (18) and the pH marker (20), is placed with acid base indicator in the described pH marker (20).
2. tumor cell drug resistance detecting chip according to claim 1, it is characterized in that: also be provided with a control group on the described chip body (1), comprise the control group nutrient solution inlet (21) that is arranged on chip body (1) surface, described control group nutrient solution inlet (21) is communicated with the control group nutrient solution passage (22) that is arranged in the chip body (1), told control group tubule (23) on the described control group nutrient solution passage (22), described control group tubule (23) is provided with cellular control unit pond (24), described contrast culture liquid passage (22), control group tubule (23) the other end connects cellular control unit access road (25), described cellular control unit access road (25) communicates with cellular control unit inlet (26), described cell pool (18) bottom is provided with pH marker (27), be provided with the penetrating film of control group carbonic acid gas (5) between described cellular control unit pond (24) and the control group pH marker (27), be placed with acid base indicator in the described control group pH marker (27).
3. tumor cell drug resistance detecting chip according to claim 1 and 2, it is characterized in that: described chip body (1) comprises glass substrate (2) and is positioned at the silica gel chip (3) on glass substrate (2) top that described pH marker (20) is positioned on the glass substrate (2).
4. tumor cell drug resistance detecting chip according to claim 1 is characterized in that: the cell pool (18) on the described tubule (17) has two at least.
5. tumor cell drug resistance detecting chip according to claim 1 is characterized in that: described tubule (17) is provided with many.
6. tumor cell drug resistance detecting chip according to claim 2 is characterized in that: described control group tubule (23) is provided with many.
7. tumor cell drug resistance detecting chip according to claim 2 is characterized in that: the cellular control unit pond (24) on the described control group tubule (23) has two at least.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910258600A CN101705179A (en) | 2009-12-13 | 2009-12-13 | Tumor cell drug resistance detecting chip |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910258600A CN101705179A (en) | 2009-12-13 | 2009-12-13 | Tumor cell drug resistance detecting chip |
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| CN101705179A true CN101705179A (en) | 2010-05-12 |
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| CN200910258600A Pending CN101705179A (en) | 2009-12-13 | 2009-12-13 | Tumor cell drug resistance detecting chip |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102952752A (en) * | 2011-08-29 | 2013-03-06 | 东南大学 | Culture inspection device for cancer cells |
| CN106661530A (en) * | 2014-07-07 | 2017-05-10 | J·逸夫 | Microfluidic device |
| CN107855141A (en) * | 2017-10-09 | 2018-03-30 | 宁波大学 | The drive device and cascade control method that particle moves in terminal closing microchannel |
-
2009
- 2009-12-13 CN CN200910258600A patent/CN101705179A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102952752A (en) * | 2011-08-29 | 2013-03-06 | 东南大学 | Culture inspection device for cancer cells |
| CN106661530A (en) * | 2014-07-07 | 2017-05-10 | J·逸夫 | Microfluidic device |
| CN106661530B (en) * | 2014-07-07 | 2021-06-04 | 阿斯特瑞格诊断公司 | Microfluidic device |
| CN107855141A (en) * | 2017-10-09 | 2018-03-30 | 宁波大学 | The drive device and cascade control method that particle moves in terminal closing microchannel |
| CN107855141B (en) * | 2017-10-09 | 2020-06-16 | 宁波大学 | Driving device for particle movement in terminal closed microchannel and cascade control method |
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Open date: 20100512 |