Drug screening platform for simulating tumor microenvironment
By designing a drug screening platform that simulates the tumor microenvironment, and utilizing chemical reactions and heating equipment to simulate the tumor microenvironment, precise interaction between drugs and cell hydrogels was achieved, solving the problem of inaccurate test results in existing technologies and improving test efficiency and accuracy.
Patent Information
- Application Number
- CN202411304543.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-19
- Publication Date
- 2026-03-20
AI Technical Summary
Existing drug screening platforms struggle to accurately simulate the tumor microenvironment, leading to inaccurate test results.
A drug screening platform simulating the tumor microenvironment was designed, comprising a tumor microenvironment simulation wafer, a drug testing wafer, and a permeable membrane. It generates acidic gas, alkaline gas, and oxygen concentration through chemical reactions, and uses heating equipment to simulate a warm chemotherapy environment, thereby realizing the interaction between drugs and cell hydrogels in the simulated tumor microenvironment.
It achieves precise interaction between drugs and cell hydrogels in a simulated tumor microenvironment, obtains accurate test results, and can simultaneously test multiple drugs and cells, thus improving testing efficiency.
Smart Images
Figure CN121703370A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present invention relates to a drug screening platform, in particular, to a drug screening platform simulating tumor microenvironment. BACKGROUND
[0002] The effect of cancer treatment is closely related to tumor microenvironment. Therefore, if a drug screening platform for testing to screen cancer treatment drugs has the function of simulating tumor growth microenvironment, accurate test results can be obtained. Such a drug screening platform, for example, the drug screening platform simulating intraperitoneal hyperthermic chemotherapy disclosed by the inventor in Taiwan Invention Patent No. TW I795812B, arranges cells into a three-dimensional structure by dielectrophoresis force to construct a three-dimensional tumor microenvironment. SUMMARY
[0003] The purpose of the present invention is to provide a drug screening platform that simulates tumor microenvironment in a novel way.
[0004] The drug screening platform of the present invention simulating tumor microenvironment is suitable for the interaction of therapeutic drugs and cell hydrogel, comprising a tumor microenvironment simulation wafer, a drug test wafer, and a permeable membrane.
[0005] The tumor microenvironment simulation wafer includes a microenvironment establishment unit for chemical reactions to produce acidic gas, basic gas and / or oxygen concentration for simulating tumor microenvironment.
[0006] The drug test wafer includes a test unit for the interaction of the therapeutic drugs and the cell hydrogel, and the orthographic projection of the test unit falls on the microenvironment establishment unit.
[0007] The permeable membrane is arranged between the tumor microenvironment simulation wafer and the drug test wafer, and the permeable membrane is used for the diffusion of acidic gas, basic gas and / or oxygen concentration produced in the microenvironment establishment unit to the test unit.
[0008] The drug screening platform of the present invention simulating tumor microenvironment, the microenvironment establishment unit has two chemical reaction zones arranged opposite to each other, each chemical reaction zone has a plurality of reaction chambers arranged at intervals, and the chemical reaction is carried out in the reaction chamber.
[0009] The drug screening platform of the present invention simulating tumor microenvironment, the tumor microenvironment simulation wafer further includes an input unit and an output unit in communication with the microenvironment establishment unit.
[0010] The drug screening platform simulating tumor microenvironment of the present application, the input unit has two input flow channels arranged opposite to each other and connected to the chemical reaction zone respectively, each input flow channel has multiple injection sections, and multiple shunt sections communicating the injection sections with the reaction chambers.
[0011] The drug screening platform simulating tumor microenvironment of the present application, the output unit has two output flow channels arranged between the chemical reaction zones and connected to the chemical reaction zones respectively, each output flow channel has a discharge section bifurcated to communicate with the corresponding reaction chamber.
[0012] The drug screening platform simulating tumor microenvironment of the present application, the test unit has two test zones arranged opposite to each other, each test zone has multiple test chambers arranged at intervals, and the interaction between the therapeutic drugs and the cell hydrogel is carried out in the test chambers.
[0013] The drug screening platform simulating tumor microenvironment of the present application, the drug test wafer further comprises a flow channel unit communicating with the test unit.
[0014] The drug screening platform simulating tumor microenvironment of the present application, the flow channel unit has a first flow channel part and two second flow channel parts.
[0015] The first flow channel part is arranged between the test zones and connected to the test zones, the first flow channel part has multiple first inlets and outlets spaced from each other, and a multi-branch connection section connecting the first inlets and outlets in series and bifurcated to communicate the first inlets and outlets with the test chambers.
[0016] The second flow channel parts are arranged opposite to each other and connected to the test zones respectively, each second flow channel part has multiple shunt structures connected to adjacent test zones, each shunt structure has two hole parts spaced from each other, and a receiving section bifurcated to communicate the hole parts with adjacent test chambers.
[0017] The drug screening platform simulating tumor microenvironment of the present application further comprises a heating device for heating the drug test wafer.
[0018] The drug screening platform simulating tumor microenvironment of the present application, the heating device comprises a heating device, a temperature measuring device and a temperature control device, the heating device is used to heat the drug test wafer, the temperature measuring device is used to measure the temperature of the drug test wafer to generate a signal, and the temperature control device is used to receive the signal to control the heating temperature of the heating device.
[0020] The beneficial effect of the present application is that in the drug screening platform of the present application simulating tumor microenvironment, the microenvironment establishment unit of the wafer for simulating tumor microenvironment can chemically simulate the concentration of acidic gas, basic gas and / or oxygen gas for simulating tumor microenvironment, which diffuses to the test unit of the wafer for drug testing through the permeable membrane, so that the therapeutic drug in the test unit and the cell hydrogel can interact in the simulated tumor microenvironment, thereby obtaining accurate and correct test results. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 is a top view schematic diagram of an embodiment of the drug screening platform of the present application simulating tumor microenvironment;
[0022] Figure 2 is a side view schematic diagram of the embodiment;
[0023] Figure 3 is a top view of a wafer for simulating tumor microenvironment of the embodiment; and
[0024] Figure 4 is a top view of a wafer for drug testing of the embodiment. DETAILED DESCRIPTION
[0025] The present application will be described in detail below in conjunction with the drawings and embodiments.
[0026] Referring to Figure 1 and Figure 2 , an embodiment of the drug screening platform of the present application simulating tumor microenvironment comprises a wafer for simulating tumor microenvironment 1, a wafer for drug testing 2, a permeable membrane 3 and a heating device 4.
[0027] Referring to Figure 1 and Figure 3 , the wafer for simulating tumor microenvironment 1 comprises a microenvironment establishment unit 11, an input unit 12 and an output unit 13 in communication with the microenvironment establishment unit 11. The microenvironment establishment unit 11 is used for chemical reaction to generate the concentration of acidic gas, basic gas and / or oxygen gas for simulating tumor microenvironment. The microenvironment establishment unit 11 has two chemical reaction zones 110 arranged opposite to each other, each chemical reaction zone 110 has a plurality of reaction chambers 111 arranged at intervals, and the chemical reaction is carried out in the reaction chambers 111. The number of reaction chambers 111 can be flexibly adjusted according to actual needs, and in the present embodiment, each chemical reaction zone 110 has three reaction chambers 111.
[0028] The input unit 12 is used to input chemicals for the chemical reaction into the microenvironment establishing unit 11. The input unit 12 has two input flow channels 120 arranged in opposite directions and connected to the chemical reaction zones 110 respectively, each of the input flow channels 120 has a plurality of injection sections 121 and a plurality of distribution sections 122 connecting the injection sections 121 and the reaction chambers 111. The number of the injection sections 121 and the distribution sections 122 can be adjusted flexibly according to the actual needs and the number of the reaction chambers 111, and in the embodiment, each of the input flow channels 120 has two injection sections 121 and three distribution sections 122.
[0029] The output unit 13 is used to discharge the waste liquid generated after the chemical reaction from the microenvironment establishing unit 11. The output unit 13 has two output flow channels 130 arranged between the chemical reaction zones 110 and connected to the chemical reaction zones 110 respectively, each of the output flow channels 130 has an exhaust section 131 bifurcated and connected to the corresponding reaction chamber 111.
[0030] The basic gas generated in the microenvironment establishing unit 11, for example, ammonia, is generated by the reaction of sodium hydroxide aqueous solution and ammonium chloride aqueous solution input into the microenvironment establishing unit 11 by the input unit 12. The acidic gas, for example, carbon dioxide, is generated by the reaction of hydrochloric acid and sodium carbonate aqueous solution input into the microenvironment establishing unit 11 by the input unit 12. The oxygen concentration is generated by the reaction of cobalt sulfate and sodium sulfite aqueous solution input into the microenvironment establishing unit 11 by the input unit 12, and the cobalt sulfate catalyzes the reaction of the sodium sulfite aqueous solution to consume the oxygen in the microenvironment establishing unit 11. After the above reactions, the waste liquid is discharged through the output unit 13.
[0031] Referring to Figure 1 and Figure 4 , the drug test wafer 2 includes a test unit 21 and a flow channel unit 22 connected to the test unit 21. The test unit 21 is used as a space for the therapeutic drug and the cell hydrogel to interact with each other, and the orthographic projection of the test unit 21 falls on the microenvironment establishing unit 11. The test unit 21 has two test zones 210 arranged in opposite directions, each of the test zones 210 has a plurality of test chambers 211 arranged at intervals, and the interaction between the therapeutic drug and the cell hydrogel is carried out in the test chambers 211. The number of the test chambers 211 can be adjusted flexibly according to the actual needs, and in the embodiment, each of the test zones 210 has nine test chambers 211.
[0032] The flow channel unit 22 has a first flow channel section 221 disposed between and connected to the test zones 210, and two second flow channel sections 222 disposed opposite to each other and respectively connected to the test zones 210. The first flow channel section 221 has a plurality of first inlets and outlets 221A spaced apart from each other, and a multi-branched connecting section 221B that connects the first inlets and outlets 221A to the test chamber 211. Each second flow channel section 222 has a plurality of diversion structures 222A connected to the adjacent test zone 210, each diversion structure 222A having two spaced apart holes 222B, and a branched receiving section 222C that connects the holes 222B to the adjacent test chamber 211. The number of the first inlet / outlet 221A and the diversion structure 222A can be flexibly adjusted according to actual needs. In this embodiment, the first flow channel 221 has three first inlets / outlets 221A, and each second flow channel 222 has three diversion structures 222A (one diversion structure 222A is connected to three test chambers 211).
[0033] The therapeutic drug is injected from the first inlet 221A of the first flow channel 221 and diverted to the test area 210. Excess therapeutic drug in the test area 210 is discharged through the orifice 222B of the second flow channel 222. Furthermore, in this embodiment, there are three first inlets 221A, so different types of therapeutic drugs can be injected independently into each of the different first inlets 221A. That is, in this embodiment, three therapeutic drugs can be injected, such as, but not limited to, cisplatin, docetaxel, and paclitaxel. The multi-branched connecting section 221B automatically diverts each of the three therapeutic drugs separately into the corresponding test chamber 211, and also diverts the three therapeutic drugs into the corresponding test chamber 211 after mixing them in different combinations (mixing the first therapeutic drug with the second therapeutic drug, mixing the second therapeutic drug with the third therapeutic drug, and mixing the first therapeutic drug with the third therapeutic drug). Figure 4To further illustrate, the first therapeutic drug is injected through the first inlet / outlet 221A on the left, the second therapeutic drug is injected through the first inlet / outlet 221A in the middle, and the third therapeutic drug is injected through the first inlet / outlet 221A on the right. After being automatically diverted via the multi-branched connecting section 221B, in the nine upper test chambers 211, the three test chambers 211 on the left contain a mixture of the first and second therapeutic drugs, the three test chambers 211 in the middle contain the second therapeutic drug, and the three test chambers 211 on the right contain a mixture of the second and third therapeutic drugs. In the nine lower test chambers 211, the three test chambers 211 on the left contain the first therapeutic drug, the three test chambers 211 in the middle contain a mixture of the first and third therapeutic drugs, and the three test chambers 211 on the right contain the third therapeutic drug.
[0034] The cell hydrogel is injected from the orifice 222B of the second flow channel 222 and diverted to the corresponding test area 210. Excess cell hydrogel in the test area 210 is discharged through the first inlet 221A of the first flow channel 221. The cell hydrogel is composed of cells and hydrogel, and the types of cells include, but are not limited to, cancer cells, stromal cells, and fibroblasts. Due to the design and combination of the test unit 21 and the flow channel unit 22, a single type of cell hydrogel or two different types of cell hydrogel can be injected from the orifice 222B. Specifically, a first type of cell hydrogel can be injected from one of the orifices 222B of each diversion structure 222A, and a second type of cell hydrogel can be injected from the other orifice 222B of each diversion structure 222A. The receiving section 222C of each diversion structure 222A automatically diverts the first and second types of cell hydrogels separately into their respective test chambers 211, and also mixes the first and second types of cell hydrogels before diverting them into their respective test chambers 211. Figure 4 One of the diversion structures 222A further illustrates this: after the first type of cell hydrogel is injected from the left orifice 222B, it will be diverted via the receiving section 222C to the left and middle test chambers 211; after the second type of cell hydrogel is injected from the right orifice 222B, it will be diverted via the receiving section 222C to the right and middle test chambers 211. Therefore, the left test chamber 211 contains the first type of cell hydrogel, the middle test chamber 211 contains a mixture of the first type of cell hydrogel and the second type of cell hydrogel, and the right test chamber 211 contains the second type of cell hydrogel.
[0035] As can be seen from the above, this embodiment is suitable for simultaneous testing of three therapeutic drugs and two cell hydrogels. Therefore, this embodiment can more effectively screen drugs and obtain multiple test results in a single test.
[0036] In one embodiment, the cell hydrogel is first injected into the orifice 222B, allowing it to flow into the test area 210. Then, excess cell hydrogel is flushed away through the first inlet / outlet 221A with a buffer solution, and discharged from the orifice 222B. After the cell hydrogel in the test area 210 is fixed, the therapeutic drug is infused through the first inlet / outlet 221A using an external automatic pump perfusion device (not shown), allowing the therapeutic drug to flow into the test area 210. The use of the automatic pump perfusion device to infuse the therapeutic drug simulates the treatment scenario of injecting chemotherapy drugs into the abdominal or thoracic cavity via perfusion during hyperthermic chemotherapy.
[0037] See Figure 2 The permeable film 3 is disposed between the drug testing wafer 2 and the tumor microenvironment simulation wafer 1. The permeable film 3 allows acidic gases, alkaline gases, and / or oxygen concentrations generated in the microenvironment establishment unit 11 to diffuse into the testing unit 21, thereby simulating an acidic, alkaline, and / or different oxygen concentration tumor microenvironment in the testing unit 21, allowing the therapeutic drug and the cell hydrogel to interact within this simulated tumor microenvironment. The material of the permeable film 3 is not limited, as long as it is gas-permeable and can isolate the microenvironment establishment unit 11 from the testing unit 21. In this embodiment, the permeable film 3 is made of polydimethylsiloxane (PDMS).
[0038] See Figure 1 The heating device 4 includes a heating element 41, a temperature measuring device 42, and a temperature control device 43. The heating element 41 heats the drug test wafer 2, the temperature measuring device 42 measures the temperature of the drug test wafer 2 to generate a signal, and the temperature control device 43 receives the signal to control the heating temperature of the heating element 41. Heating the drug test wafer 2 using the heating device 4 simulates the treatment scenario of injecting heated chemotherapy drugs into the abdominal or thoracic cavity during hyperthermic chemotherapy. A warm tumor microenvironment is simulated in the test unit 21 of the drug test wafer 2, allowing the therapeutic drug and the cell hydrogel to interact within this simulated tumor microenvironment.
[0039] In summary, the drug screening platform for simulating the tumor microenvironment of this invention uses the microenvironment establishment unit 11 to chemically simulate the concentrations of acidic gases, alkaline gases, and / or oxygen used to simulate the tumor microenvironment. These concentrations diffuse through the permeable membrane 3 to the test unit 21 of the drug testing wafer 2, and are selectively simulated as a warm tumor microenvironment within the test unit 21 by the heating device 4. This allows the therapeutic drugs and cell hydrogels in the test unit 21 to interact within the simulated tumor microenvironment, thereby obtaining accurate test results. Furthermore, through the design and combination of the test unit 21 and the flow channel unit 22, three therapeutic drugs and two cell hydrogels can be selectively tested, resulting in eighteen accurate test results from a single test, thus effectively achieving the objectives of this invention.
[0040] The above description is merely an embodiment of the present invention and should not be construed as limiting the scope of the present invention. Any simple equivalent changes and modifications made in accordance with the claims and description of the present invention shall still fall within the scope of the present invention.
Claims
1. A drug screening platform simulating the tumor microenvironment, suitable for enabling the interaction between therapeutic drugs and cell hydrogels, characterized in that, The drug screening platform simulating the tumor microenvironment includes: A chip for simulating a tumor microenvironment includes a microenvironment creation unit, which is used for chemical reactions to generate acidic gas, alkaline gas, and / or oxygen concentrations to simulate a tumor microenvironment. A wafer for drug testing includes a test unit for the interaction of the therapeutic drug with the cell hydrogel, and the orthographic projection of the test unit falls on the microenvironment establishment unit; and A permeable membrane is disposed between the wafer used to simulate the tumor microenvironment and the wafer used for drug testing, and is used to allow the concentration of acidic gases, alkaline gases and / or oxygen generated in the microenvironment establishment unit to diffuse into the test unit.
2. The drug screening platform simulating the tumor microenvironment according to claim 1, characterized in that: The microenvironment establishment unit has two chemical reaction zones arranged opposite each other, and each chemical reaction zone has multiple reaction chambers arranged at intervals, in which the chemical reaction is carried out.
3. The drug screening platform for simulating the tumor microenvironment according to claim 2, characterized in that: The chip for simulating the tumor microenvironment also includes an input unit and an output unit connected to the microenvironment establishment unit.
4. The drug screening platform simulating the tumor microenvironment according to claim 3, characterized in that: The input unit has two input channels that are arranged opposite to each other and are respectively connected to the chemical reaction zone. Each input channel has multiple injection sections and multiple branch sections that connect the injection sections to the reaction chamber.
5. The drug screening platform simulating the tumor microenvironment according to claim 3, characterized in that: The output unit has two output channels disposed between and connected to the chemical reaction zones, each output channel having a branched discharge section that communicates with the corresponding reaction chamber.
6. The drug screening platform for simulating the tumor microenvironment according to claim 1, characterized in that: The experimental unit has two experimental zones arranged opposite each other, and each experimental zone has multiple experimental chambers arranged at intervals, in which the interaction between the therapeutic drug and the cell hydrogel is carried out.
7. The drug screening platform for simulating the tumor microenvironment according to claim 6, characterized in that: The drug testing wafer also includes a flow channel unit that connects to the testing unit.
8. The drug screening platform for simulating the tumor microenvironment according to claim 7, characterized in that: The flow channel unit has A first flow channel is disposed between and connects the test zones. The first flow channel has a plurality of first inlets and outlets spaced apart from each other, and a multi-branched connecting section that connects the first inlets and outlets to the test chamber by branching into multiple branches. Two second flow channels are arranged opposite each other and connected to the test area respectively. Each second flow channel has multiple flow-diverting structures connected to the adjacent test area. Each flow-diverting structure has two spaced-apart orifices and a branched receiving section that connects the orifices to the adjacent test chamber.
9. The drug screening platform simulating the tumor microenvironment according to claim 1, characterized in that: The drug screening platform simulating the tumor microenvironment also includes a heating device for heating the wafers used in drug testing.
10. The drug screening platform for simulating the tumor microenvironment according to claim 9, characterized in that: The heating device includes a heating element, a temperature measuring element, and a temperature control element. The heating element is used to heat the drug test wafer, the temperature measuring element is used to measure the temperature of the drug test wafer to generate a signal, and the temperature control element is used to receive the signal to control the heating temperature of the heating element.