Centrifugal screening device
Patent Information
- Application Number
- TW114112615
- Authority / Receiving Office
- TW · TW
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-04-01
- Publication Date
- 2026-10-16
- Estimated Expiration
- 2045-03-31
AI Technical Summary
Existing drug screening processes are time-consuming and labor-intensive due to the difficulty in separating and screening reagents at different concentration ratios.
A centrifugal screening device comprising an inner disk with dendritic network channels and an outer ring, which allows for the rapid generation of concentration gradients and automation of cell culture operations through a combination of inner discs and outer rings, enabling efficient and low-cost drug screening.
The device provides an automated, efficient, and cost-effective platform for drug screening by rapidly generating concentration gradients and automating cell culture operations, replacing traditional labor-intensive methods.
Smart Images
Figure TWG2TA001079953_001 
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Abstract
Description
[Technical Field]
[0001] A screening device, more specifically, relates to a centrifugal screening device for a specific substance, such as a reagent, medicine, cell or drug, on a centrifugation platform. [Previous Technology]
[0002] Drug screening is a step in the modern drug development process to test and obtain compounds with specific physiological activities. Essentially, drug screening involves conducting pharmacological activity experiments on compounds. As a screening process, it requires cross-sectional comparisons of the physiological activities of different compounds; therefore, the experimental protocols for drug screening need to be standardized and quantitative. However, in existing drug screening processes, separating and screening reagents at different concentration ratios is quite time-consuming and labor-intensive. [Summary of the Invention]
[0003] To replace the traditional, time-consuming and labor-intensive drug screening experiments and provide a more efficient and accurate screening platform, the present invention provides a centrifugal screening device, which includes a fluidly connected inner disk and an outer ring, wherein: the inner disk includes a circular disk-shaped base and a circular upward-protruding concentration preparation stage; the concentration preparation stage has a semi-circular adjacent and concave first reagent tank and a second reagent tank arranged from the center, and a fluidly connected first dendritic network channel and a second dendritic network channel extend outward from the bottom of the first reagent tank and the second reagent tank respectively; the outer edge of the concentration preparation stage includes several outward protrusions and several inward concave platforms forming a toothed disk-shaped platform; the first dendritic network channel and the second dendritic network channel are curved dendritic microchannels and include several liquid mixing points for mutual liquid flow; the first dendritic network channel and the second dendritic network channel extend to the end of the concentration preparation stage and are provided with several liquid outlets, each liquid outlet corresponding to the outward protrusion of the concentration preparation stage; The outer ring is a hollow ring with an inner disc fitting hole in its center. The edge of the hole forms a toothed disc-shaped hole with several protrusions and concave platforms on the outer edge of the concentration setting platform, allowing the outer ring to be detachably fitted and fixed to the inner disc. The outer ring includes, from the edge of the inner disc fitting hole outwards, a liquid receiving hole, a sample chamber, a metering channel, a siphon channel, a waste liquid drainage chamber, and a waste liquid chamber. The liquid receiving hole corresponds to the liquid outlet at the end of the concentration setting platform and connects to the sample chamber. The sample chamber is a receiving space with the metering channel on its right side connecting to the waste liquid drainage chamber and the siphon channel on its bottom left side connecting to the waste liquid chamber.
[0004] Preferably, in some embodiments, the outer edge of the concentration configuration stage includes ten protrusions and ten recesses.
[0005] Wherein, the waste liquid drainage cavity is a left-right extending arc-shaped chamber; the cross-section of each individual tree-like network channel is between 0.1 and 0.9 mm; and the accommodating space is a circular accommodating space.
[0006] The inner disk and the outer ring are assembled and then rotated in different directions and at different speeds using a centrifugal platform.
[0007] In the wetting stage of the centrifugal screening device, the inner disk is assembled with the empty outer ring, a wetting liquid is loaded into the first reagent tank and the second reagent tank of the inner disk, and the centrifugal screening device is rotated as a whole, so that the wetting liquid fills the first dendritic network channel and the second dendritic network channel, and removes air bubbles in the first dendritic network channel and the second dendritic network channel.
[0008] In the first replacement stage, the centrifugal screening device loads a first reagent and a second reagent into the first reagent tank and the second reagent tank respectively, and rotates the centrifugal screening device to replace the wet liquid in the first dendritic network channel and the second dendritic network channel with the first reagent and the second reagent. The excess wet liquid is collected in the waste liquid chamber of the outer ring.
[0009] In the sample addition stage, after the outer ring used in the wetting stage and the substitution stage is removed from the centrifugal screening device, a second outer ring containing a sample cavity is assembled with the inner disk of the wetting stage and the substitution stage. Then, the first reagent and the second reagent are put back into the corresponding first reagent tank and second reagent tank. The centrifugal screening device is rotated so that the mixed solutions of the first reagent and the second reagent of different concentrations flow into each sample cavity under centrifugation. The excess mixed solutions of the first reagent and the second reagent are sent to the waste liquid chamber through the metering channel to measure the concentration of the mixed solution in each sample cavity.
[0010] In the process of the centrifugal screening device in a culture stage: the outer ring of the sample addition stage is then removed from the inner plate and assembled with another inner plate, and the centrifugal screening device is placed in an incubator for culture.
[0011] Wherein, when the centrifugal screening device is in the emptying stage, after cultivation, the centrifugal screening device is taken out from the incubator and placed on the centrifuge platform to rotate and discharge the liquid.
[0012] Wherein, the wetting liquid contains ethanol; the first reagent and / or the second reagent contains a drug solution and / or a mixture of cell culture medium solutions; and the sample contains a cell culture wafer.
[0013] As can be seen from the above description, the present invention has the following beneficial effects and advantages:
[0014] 1. This invention develops an automated microfluidic centrifugal screening device based on a centrifugation platform. One application is cell drug screening, which can replace the traditional time-consuming and labor-intensive drug screening experiments. This centrifugal screening device mainly consists of an inner disc and an outer ring. The inner disc contains a branched structure, which can be used to provide a concentration gradient for cell growth. The outer ring contains multiple sets of sample chambers for placing cells and can achieve repeated quantitative and emptying of the culture medium. This invention can provide rapid generation of concentration gradients and realize the automation of cell culture operations, providing an efficient and low-cost platform for drug screening.
[0015] 2. This invention develops a microfluidic centrifugal screening device with a concentration gradient generation effect. Through a tree-like structure, two reagents are distributed into multiple gradient-distributed mixed concentrations, which are then used to test the drug concentration of cells. The concept of combining inner discs and outer rings is used for replaceable functional unit discs and integrated into an automated centrifugal chromatography platform, thereby developing an automated process and saving the cost of cell drug screening.
Implementation Method
[0016] The present invention will be described and illustrated in detail below with reference to several preferred embodiments. The accompanying drawings are merely some exemplary representations or embodiments of the present invention. For those skilled in the art, the present invention can be applied to other similar situations based on these drawings without any further effort.
[0017] The terms “system,” “apparatus,” “unit,” and / or “module” used in this invention are to distinguish different components, elements, parts, sections, or assemblies at different levels. However, if other words can achieve the same purpose, they may be replaced by other expressions. As shown in this invention, unless the context clearly indicates otherwise, words such as “a,” “an,” “an,” and / or “the” do not specifically refer to the singular and may also include the plural. Generally speaking, the terms “comprising” and “including” only indicate the inclusion of explicitly identified steps and elements, which do not constitute an exclusive list, and the method or apparatus may also include other steps or elements.
[0018] Flowcharts are used in this invention to illustrate the operations performed by the system according to embodiments of the invention. It should be understood that the preceding or following operations are not necessarily performed precisely in sequence. Instead, the steps can be processed in reverse order or simultaneously. Furthermore, other operations can be added to these processes, or one or more steps can be removed from them.
[0019] Please refer to Figures 1 to 7, which show a centrifugal screening device 100 of the present invention, which includes an inner disk 10 and an outer ring 20 in fluid communication.
[0020] <Inner Plate Example 1>
[0021] The first preferred embodiment of the inner disk 10 of the present invention is shown in Figures 1-3, which includes a circular disk-shaped base 11 and a circular upward protruding concentration distribution platform 12.
[0022] The concentration preparation platform 12 has a semi-circular, adjacent, and concave first reagent tank 121 and a second reagent tank 122 at its center, and fluid-connected first tree-like network channels 1211 and second tree-like network channels 1221 extend outward from the bottom of the first reagent tank 121 and the second reagent tank 122, respectively. The outer edge of the concentration preparation platform 12 includes several outward protrusions 124 and several inward concave platforms 125 forming a toothed disc-shaped platform. The preferred embodiment of FIG1 includes ten outward protrusions 124 and ten inward concave platforms 125.
[0023] The first tree-like network channel 1211 and the second tree-like network channel 1221 are curved tree-like microchannels and contain several liquid mixing points 123 through which liquid flows between each other. The cross-section of each individual tree-like network channel is preferably between 0.1 and 0.9 mm, for example, 0.2 mm.
[0024] The first tree network channel 1211 and the second tree network channel 1221 extend to the end of the concentration configuration platform 12 and are provided with several liquid outlets 13, each liquid outlet 13 being provided with the outer protrusion 124 of the concentration configuration platform 12.
[0025] <Inner Plate Example 2>
[0026] The second preferred embodiment of the inner disk 10 of the present invention is basically the same as the first preferred embodiment described above, but this embodiment does not include the microchannel structure of the first tree network channel 1211 and the second tree network channel 1221.
[0027] <External Ring Example 1>
[0028] The outer ring 20 is a hollow annular structure, as shown in Figure 1. It has an inner disc fitting hole 21 within its ring. The edge of the hole corresponds to several external protrusions 124 and several internal concave platforms 125 included on the outer edge of the concentration distribution platform 12, forming a toothed disc-shaped hole, allowing the outer ring 20 to be detachably fitted and fixed to the inner disc 10. Structurally, the outer ring 20 includes, from the edge of the inner disc fitting hole 21, a liquid receiving hole 22, a sample cavity 23, a metering channel 24, a siphon channel 25, a waste liquid drainage cavity 26, and a waste liquid cavity 27.
[0029] The liquid receiving hole 22 corresponds to the liquid outlet 13 at the end of the concentration preparation station 12, and is used to receive the liquid discharged from the liquid outlet 13 and connect to the sample chamber 23. The sample chamber 23 is a receiving space, which is circular in this embodiment. The metering channel 24 is provided on the right side of the sample chamber 23 and connects to the waste liquid drainage chamber 26. The siphon channel 25 is provided at the bottom left side of the sample chamber 23 and finally connects to the waste liquid chamber 27.
[0030] The waste liquid drainage chamber 26 is an arc-shaped chamber extending to the left and right, which can respectively receive the liquid discharged from the metering channel 24 and the siphon channel 25, and drain it from the waste liquid chamber 27 in an arc-shaped design.
[0031] <Usage Procedure>
[0032] Please refer to Figures 7-9. In a preferred embodiment of the centrifugal screening device 100 of the present invention, it is used as a cell drug screening platform. In use, the inner disk 10 and the outer ring 20 are first assembled and then rotated at different speeds using a centrifugal platform (e.g., a rotary centrifuge). The process mainly includes five stages: I. wetting, II. substitution, III. sample addition, IV. culture, and V. emptying.
[0033] Stage I Wetting Stage: In the wetting stage, the inner disk 10 (Example 1) is assembled with the empty outer ring 20. A wetting liquid L (e.g., ethanol) with low surface tension and low contact angle is filled into the first reagent tank 121 and the second reagent tank 122 of the inner disk 10, and the centrifugal screening device 100 is rotated clockwise (CW) to 1500 RPM. Because the wetting liquid L has low surface tension and a low contact angle with the surface of the inner disk 10, the wetting liquid L can easily fill the first dendritic network channel 1211 and the second dendritic network channel 1221, and a bubble D formed in the curved dendritic microchannel during this process can be removed by the flow of the wetting liquid L.
[0034] Stage II Replacement Stage: After the first dendritic network channel 1211 and the second dendritic network channel 1221 are filled with ethanol, a first reagent A (e.g., a drug solution) and a second reagent B (e.g., a cell culture medium mixture solution) are respectively loaded into the first reagent tank 121 and the second reagent tank 122, and the centrifugal screening device 100 is rotated clockwise to 2000 RPM (CW). The moist liquid L in the first dendritic network channel 1211 and the second dendritic network channel 1221 is replaced by the first reagent A and the second reagent B, and the excess moist liquid L is subsequently collected by the waste liquid chamber 27 of the outer ring 20.
[0035] Stage III Sample Addition Stage: After removing the outer ring 20 used in Stage I, the second outer ring 20 containing a cell culture wafer C in the sample chamber 23 is assembled with the inner disk 10 of Stage I. The first reagent A and the second reagent B are then loaded back into the corresponding first reagent tank 121 and second reagent tank 122, and the centrifugal screening device 100 is rotated clockwise to 2000 RPM (CW). The mixed solutions of the first reagent A and the second reagent B at different concentrations flow into each sample chamber 23 under centrifugation. Then, the excess A and B mixed solution is sent to the waste liquid chamber 27 through the metering channel 24 to measure the concentration of the mixed solution in each sample chamber 23.
[0036] Stage IV Culture Stage: Then, the outer ring 20 of Stage II is removed and assembled with the inner disc 10 (Example 2), and the centrifugal screening device 100 is placed in an incubator. Since the inner disc 10 (Example 2) does not contain a microchannel structure, it is used to seal the liquid receiving hole 22 of the outer ring 20 when liquid filling is not required in this Stage IV culture stage and the subsequent Stage V emptying stage. The inner disc 10 (Example 2) seals the inlet of the inner disc 10 (Example 2) and prevents liquid leakage from the outer ring 20 during the Stage IV culture stage. For repeat experiments, a new outer ring 20 containing the cell culture wafer C can be assembled with the inner disc 10 (Example 1) to repeat the sample loading process.
[0037] Stage Five V Emptying Stage: After cultivation, the centrifugal screening device 100, consisting of the inner disk 10 (Example 2 empty disk) and the outer ring 20 containing the cell culture wafer C, is removed from the incubator and placed on a centrifuge platform for liquid discharge. The rotation speed of the centrifugal screening device 100 is increased to 3000 RPM (CW), and then rapidly reduced to 1000 RPM in a counterclockwise (CCW) direction, with an angular acceleration of 50,000 RPM / s. This action results in an Euler-assisted siphon effect, through which the liquid in the sample chamber 23 is discharged into the waste liquid chamber 27 via the siphon channel 25. Finally, the centrifugal screening device 100 rotates at 3000 RPM (CCW) to remove residual liquid in the siphon channel 25 to prevent the automatic discharge effect in the next sample loading stage.
[0038] If the cell culture and drug testing process in this embodiment continues, the centrifugal screening device 100 can repeat the drug concentration addition, culture and emptying stages.
[0039] The centrifugal screening device 100 is a cell drug screening platform. The first reagent A and the second reagent B are described in preferred embodiments as drug solution and cell culture medium mixture solution. However, the centrifugal screening device 100 provided by the present invention is based on various concentration mixtures formed by mixing the first reagent A and the second reagent B in a concentration gradient. It can be used for any chemical, biological, medical, biochemical and other applications, and is not limited here.
[0040] Flowcharts are used in this invention to illustrate the operations performed by the system according to embodiments of the invention. It should be understood that the preceding or following operations are not necessarily performed precisely in sequence. Instead, the steps can be processed in reverse order or simultaneously. Furthermore, other operations can be added to these processes, or one or more steps can be removed from them.
[0041] In some embodiments, numbers describing the quantity of components and attributes are used. It should be understood that such numbers used in the description of embodiments are modified in some examples by the terms "approximately," "approximately," or "generally." Unless otherwise stated, "approximately," "approximately," or "generally" indicates that the numbers are allowed to vary by ±20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximate values, which may be changed depending on the characteristics required by individual embodiments. In some embodiments, numerical parameters should take into account specified significant digits and employ a general method of digit reservation. Although the numerical ranges and parameters used to confirm their breadth of range in some embodiments of the invention are approximate values, in specific embodiments, such values are set as precisely as feasible.
[0042] Finally, it should be understood that the embodiments described in this invention are merely illustrative of the principles of the invention. Other modifications may also fall within the scope of this invention. Therefore, alternative configurations of the embodiments of this invention are considered as examples and not limitations, and are regarded as consistent with the teachings of this invention. Accordingly, the embodiments of this invention are not limited to those explicitly described and illustrated herein. [Simplified Explanation of the Diagram]
[0043] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are merely some examples or embodiments of the present invention and are not intended to limit the technical scope of the present invention. Unless obvious from the context or otherwise stated, the same reference numerals in the drawings represent the same structure or operation. Wherein: Figure 1 and Figure 2 are perspective views and top views of the first preferred embodiment of the inner disk of the present invention. Figure 3 is a partial enlarged view of the first preferred embodiment of the inner disk of the present invention. Figure 4 and Figure 5 are perspective views and top views of the first preferred embodiment of the outer ring of the present invention. Figure 6 is a partial enlarged view of the first preferred embodiment of the outer ring of the present invention. Figure 7 is a schematic diagram of the assembly of the outer ring and the inner disk of the present invention. Figure 8 is a schematic diagram of the rotation speed used in the preferred embodiment of the present invention. Figure 9 is a schematic diagram of the usage process of the centrifugal screening device of the present invention.
Claims
1. A centrifugal screening device comprising a fluidly connected inner disk and an outer ring, wherein: the inner disk comprises a circular disk-shaped base and a circular upwardly protruding concentration preparation platform; the concentration preparation platform has a semi-circular adjacent and concave first reagent tank and a second reagent tank at its center, and a fluidly connected first dendritic network channel and a second dendritic network channel extend outward from the bottom of the first reagent tank and the second reagent tank, respectively; the outer edge of the concentration preparation platform comprises several outward protrusions and several inward concave platforms forming a toothed disk-shaped platform; the first dendritic network channel and the second dendritic network channel are curved dendritic microchannels and include several liquid mixing points for mutual liquid flow; the first dendritic network channel and the second dendritic network channel extend to the end of the concentration preparation platform and are provided with several liquid outlets, each liquid outlet corresponding to the outward protrusion of the concentration preparation platform; The outer ring is a hollow ring with an inner disc fitting hole in its center. The edge of the hole forms a toothed disc-shaped hole with several protrusions and concave platforms on the outer edge of the concentration setting platform, allowing the outer ring to be detachably fitted and fixed to the inner disc. The outer ring includes, from the edge of the inner disc fitting hole outwards, a liquid receiving hole, a sample chamber, a metering channel, a siphon channel, a waste liquid drainage chamber, and a waste liquid chamber. The liquid receiving hole corresponds to the liquid outlet at the end of the concentration setting platform and connects to the sample chamber. The sample chamber is a receiving space with the metering channel on its right side connecting to the waste liquid drainage chamber and the siphon channel on its bottom left side connecting to the waste liquid chamber.
2. The centrifugal screening device as claimed in claim 1, wherein: the outer edge of the concentration setting platform includes ten external protrusions and ten internal recesses.
3. The centrifugal screening device as claimed in claim 1, wherein: the waste liquid drainage chamber is a left-right extending arc-shaped chamber; the cross-section of each individual tree-like network channel is between 0.1 and 0.9 mm; and the accommodating space is a circular accommodating space.
4. The centrifugal screening device as claimed in claim 1, wherein: the inner disc and the outer ring are assembled and rotated in different directions and at different speeds on a centrifugal platform.
5. The centrifugal screening device as claimed in claim 1, wherein: during a wetting stage, the inner disk is assembled with the empty outer ring, a wetting liquid is filled into the first reagent tank and the second reagent tank of the inner disk, and the centrifugal screening device is rotated as a whole, so that the wetting liquid fills the first dendritic network channel and the second dendritic network channel, and removes air bubbles from the first dendritic network channel and the second dendritic network channel.
6. The centrifugal screening apparatus as claimed in claim 5, wherein: during a replacement stage, a first reagent and a second reagent are respectively loaded into the first reagent tank and the second reagent tank, and the centrifugal screening apparatus is rotated; causing the moist liquid in the first dendritic network channel and the second dendritic network channel to be replaced by the first reagent and the second reagent, and excess moist liquid is collected in the waste liquid chamber of the outer ring.
7. The centrifugal screening device as claimed in claim 6, wherein: when the centrifugal screening device is in a sample addition stage, after the outer ring used in the aforementioned wetting stage and the substitution stage is removed, a second outer ring containing a copy of the sample chamber is assembled with the inner disc of the aforementioned wetting stage and the substitution stage, and then the first reagent and the second reagent are reloaded into the corresponding first reagent tank and the second reagent tank, the centrifugal screening device is rotated so that the mixed solutions of the first reagent and the second reagent of different concentrations flow into each sample chamber under centrifugation, and the excess mixed solution of the first reagent and the second reagent is sent to the waste liquid chamber through the metering channel to measure the concentration of the mixed solution in each sample chamber.
8. The centrifugal screening device as claimed in claim 7, wherein: during a culture stage of the centrifugal screening device: the outer ring of the sample loading stage is then removed from the inner disc and assembled with another inner disc, and the centrifugal screening device is placed in an incubator for culture.
9. The centrifugal screening device as claimed in claim 8, wherein: during a venting phase, after incubation, the centrifugal screening device is removed from the incubator and placed on a centrifuge platform to rotate and drain the liquid.
10. The centrifugal screening apparatus as claimed in any one of claims 6 to 9, wherein: the wetting liquid comprises ethanol; the first reagent and / or the second reagent comprises a drug solution and / or a mixture of cell culture media; and the sample comprises a cell culture wafer.