This Non-provisional application claims priority under 35 U.S.C. §119(a) on Patent Application No(s). 104100781 filed in Taiwan, Republic of China on Jan. 9, 2015, the entire contents of which are hereby incorporated by reference.
Field of Invention
The invention is relative to a channel device, especially relative to a centrifugal channel device.
Related Art
In regard to clinical medicine or food inspection, there is plenty of demand of specific biomolecules detection. Specifically, in regard to clinical medicine, by detecting the content of various biological molecules of the human body, such as free cells in blood, urine and other body fluids, or all kinds of the content of the protein, it can be preliminarily determined whether a human organ functions well or not. In regard to food inspection, by detecting the substance in the raw food materials or products, it can be preliminarily determined whether the foods contain excessive carcinogens, pesticides, or identified whether the food is genetically modified food or not. However, before testing, a particular biomolecule or substance in the samples (e.g. aforesaid blood, urine, and raw food materials or products, etc.) must be isolated or purified to increase the concentration of a specific subject matter, and it is advantageous to subsequent detection experiments. Therefore, the process and separation of the sample become the primary objective of enhancing biomedical detection technology.
In recent years, the microfluidic technology is applied to isolation or purification substances in the sample, such as a centrifugal-based microfluidic device. The centrifugal microfluidic device isolates or purifies the substances in the sample by centrifugal force generated by rotation. However, when centrifugal microfluidic device is in operation, only few amount of the samples can be injected into it every time. Thus, it is difficult to deal with a large number of samples and to detect the substance of which the content is low from the sample. Therefore, commercial application of centrifugal microfluidic device is limited and it is generally utilized as a research tool.
In addition, the current centrifugal microfluidic device is improved by continuous injection to deal with a large number of the samples. However, as to plenty of isolated samples, only an exhausting channel is provided. So that the isolated sample is sprayed on the peripheral edge due to centrifugal force.
In view of foregoing subject, an objective of the present invention is to provide a centrifugal channel device. The centrifugal channel device utilizes the centrifugal effect and density gradient method to isolate substances with different weights or sizes. The centrifugal channel device utilizes the waste liquid tank and the collecting unit to deal with plenty of sample. It can maintain the whole centrifugal channel device clean and avoid contamination.
For achieving above objective, an objective of the present invention is to provide a centrifugal channel device. The centrifugal channel device includes a channel body, at least one collecting unit and a waste liquid tank. The channel body includes a first surface and a second surface relatively disposed. The channel body includes a sample inlet, at least one sample channel, an isolation tank, a reagent inlet, at least one reagent channel and at least one mixing channel. The sample inlet is located on the first surface. The sample channel is connected with the sample inlet. The isolation tank is located adjacent to the sample channel and communicates with the sample channel. The reagent inlet is located on the first surface. The reagent channel communicates with the reagent inlet. One end of the mixing channel is connected with the sample channel and the reagent inlet. The collecting unit includes an opening and at least one overflow hole. The opening communicates with another end of the mixing channel. The waste liquid tank communicates with the overflow hole of the collecting unit.
In one embodiment, the overflow hole of the collecting unit is located on the second surface, and the waste liquid tank communicates with second surface of the channel body.
In one embodiment, the overflow hole of the collecting unit is located at the exterior of the channel body, and the waste liquid tank communicates with the exterior of the channel body.
In one embodiment, the waste liquid tank is detachably disposed on the channel body.
In one embodiment, the waste liquid tank includes an inner sidewall and an exterior sidewall, the second surface of the channel body has at least two hooks, the top sides of the inner sidewall and the exterior sidewall respectively has a slot, and the hooks are engaged with the slots.
In one embodiment, the second surface of the channel body has at least two protrusions and formed by extending from two sides of the hooks to surround a peripheral edge of the channel body, and the hooks and the protrusions are received in the slots of the waste liquid tank.
In one embodiment, the channel body further includes two elastic elements and the two elastic elements are disposed in the two slots.
In one embodiment, the collecting unit is detachably disposed on the channel body.
In one embodiment, a cavity or an opening is disposed in the channel body and the collecting unit is received in the cavity or the opening.
In one embodiment, the channel body includes two hollow cylinders, the two hollow cylinders are respectively disposed on the peripheral edges of the sample inlet and the reagent inlet.
In one embodiment, the channel body is disc-shaped, and the waste liquid tank is a ring-shaped slot and disposed on the second surface of the channel body or disposed surroundingly on an exterior of the channel body.
In one embodiment, a part of the sample channel extends outwardly to form the isolation tank.
In one embodiment, the sample inlet is located on the geometric center of the channel body, and the sample channel extends outwardly in a spiral manner.
For achieving above objective, an objective of the present invention is to provide a centrifugal channel device. The centrifugal channel device includes a channel body, at least one collecting unit and a waste liquid tank. The channel body includes a first surface and a second surface relatively disposed. The channel body includes at least one sample channel, at least one reagent channel and at least one mixing channel. The sample channel is disposed in the channel body. The sample channel forms a sample inlet on the first surface. A part of the sample channel extends outwardly to form an isolation tank. The reagent channel is disposed within the channel body and forms a reagent inlet on the first surface. One end of the mixing channel is connected with sample channel and the reagent inlet. The collecting unit includes an opening and at least one overflow hole. The opening communicates with another end of the mixing channel. The waste liquid tank communicates with the overflow hole of the collecting unit.
For achieving above objective, an objective of the present invention is to provide a centrifugal channel device. The centrifugal channel device includes a channel body, a waste liquid tank and at least one collecting unit. The channel body includes a first surface and a second surface relatively disposed. The channel body includes a sample inlet, at least one sample channel, an isolation tank, a reagent inlet, at least one reagent channel, at least one mixing channel and at least one first connection part. The sample inlet is disposed on the first surface. The sample channel is connected with the sample inlet. The isolation tank is located adjacent to the sample channel and communicates with the sample channel. The reagent inlet is located on the first surface. The reagent channel is connected with the reagent inlet. One end of the mixing channel communicates with the sample channel and the reagent inlet. The first connection part is disposed on the second surface. The waste liquid tank is detachably disposed on the channel body. The waste liquid tank includes at least one second connection part. The first connection part and the second connection part cooperate with each other. The collecting unit includes an opening and at least one overflow hole. The opening communicates with another end of the mixing channel. The overflow hole communicates with the waste liquid tank.
In one embodiment, the first connection part is a hook and the second connection part is a slot.
In one embodiment, the waste liquid tank includes an inner sidewall and an exterior sidewall, the second surface of the channel body includes at least two hooks, the top sides of the inner sidewall and the exterior sidewall respectively includes the at least one slot, and the two hooks are engaged with the two slot.
In one embodiment, the second surface of channel body includes at least two protrusions formed by extending from two sides of the hook to surround a peripheral edge of the channel body, and each of the two hooks and each of the two protrusions are disposed together in two slots of the waste liquid tank.
In one embodiment, the channel body further includes two elastic elements disposed in the two slots.
In one embodiment, the channel body is disc-shaped, the waste liquid tank is a ring-shaped slot, and the waste liquid tank is disposed on the second surface of the channel body or disposed surroundingly on the exterior of the channel body.
In summary, the centrifugal channel device of the present invention utilizes the flow channel design, especially the configuration relationship between the sample channel and isolation tank, to filter the sample which flows through the confluence area of the sample channel and the isolation tank by the centrifugal force and density gradient solution. Thus, the lighter cells or molecular flow into the mixing channel by centrifugal force, and the heavier cells or molecular flow into the isolation tank so as to isolate substances from the sample.
Additionally, because the waste liquid tank communicates with the overflow hole of the collecting unit, the waste liquid tank can receive the excessive sample. Thus, it can easily deal with plenty of sample, maintain the while centrifugal channel device clean and avoid contamination.
The invention will become more fully understood from the detailed description and accompanying drawings, which are given for illustration only, and thus are not limitative of the present invention, and wherein:
A centrifugal channel device of a preferred embodiment of the present invention will be apparent from the following detailed description, which proceeds with reference to the accompanying drawings, wherein the same references relate to the same elements.
For instance, in the process of Tumor Metastasis, the tumor cells from the primary site are transferred to other parts of the body far away from the primary site (e.g., other tissues or organs) in the continuous growth process. First, the tumor cells must cross or bypass the adjacent cells, and then enter the circulatory system, such as blood vessels. Then by the blood circulatory system, they are transferred to other tissues or organs. The free tumor cells in the blood are called “circulating tumor cells (CTC)”. The content of the circulating tumor cell in the blood is low, namely, it means that the proportion of the circulating tumor cells other than blood cells to the overall composition of blood samples is very low. Even in the blood that the patient's tumor cells had metastasized, usually only one circulating tumor cells exists in every 106 to 109 mononuclear cells. Thus, a large amount of blood samples is required and processed to obtain a sufficient quantity of circulating tumor cells (detection target). The centrifugal channel device C1 of the embodiment is configured for isolating the circulating tumor cells from the blood sample.
The channel body 1 is disc-shaped, namely disc-shaped with a thickness. Thus, the sample channel 14, the isolation tank 15, the reagent channel 17 and the mixing channel 18 can be formed within the channel body 1. The sample inlet 13 and the reagent inlet 16 are located on the first surface 11 of the channel body 1. The material of the channel body 1 can be plastic, such as poly methyl methacrylate (PMMA), polycarbonate (PC) or other thermoplastics and so on.
Specifically, the sample inlet 13 is disposed at the first surface 11, namely, the first surface 11 has the sample inlet 13 in the form of opening. The sample channel 14 is formed within the channel body 1 and connected with the sample inlet 13. Preferably, the sample inlet 13 is located at the geometric center of the channel body 1, and it is beneficial to continuously inject blood samples when the centrifugal channel device C1 is in operation. It should be noted that the geometric center of the embodiment is not a central point, but the area around the geometric center. Specifically, the centrifugal channel device C1 can be utilized with a rotating platform. The centrifugal force for isolation of the content from the sample is generated by the rotation of centrifugal channel device C1 driven by the rotating platform. The centrifugal channel device C1 further includes positioning holes O which are through holes. In the embodiment, there are three positioning holes O for example. The centrifugal channel device C1 can be fixed on the rotating platform by the positioning holes O. When the centrifugal channel device C1 is driven to rotate by the rotating platform, the position of the geometric center is not changed and not deviated caused by rotation. Thus, the samples can be continuously injected into the sample inlet 13. Then the centrifugal channel device C1 can be applied to experiments or detection methods for isolation of a lot of samples. The configuration of the channel body 1 of the embodiment is not limited to those presented in the embodiment of the present invention. It should be provided with stable rotation to generate the centrifugal force. Preferably, the channel body 1 is disc-shaped.
Similarly, the reagent inlet 16 is disposed at the first surface 11, namely, the first surface 11 has the reagent inlet 16 in the form of opening. The reagent channel 17 is similarly disposed within the channel body 1 and connected with the reagent inlet 16. Preferably, the reagent inlet 16 may be located at the geometric center of the channel body 1, or the zone around the geometric center. In the embodiment, the sample inlet 13 and the reagent inlet 16 have same shapes but different dimensions. Thus, the sample inlet 13 and the reagent inlet 16 can be together located at the geometric center of the channel body 1, the sample inlet 13 is located at inner side, and the reagent inlet 16 is located at exterior side. Preferably, the sample inlet 13 and the reagent inlet 16 are circular openings, and they are located at the geometric center in a concentric manner. Thus, not only the samples, the reagents are also injected continuously. In operation, when the centrifugal channel device C1 operates, the sample such as blood sample is injected into the sample inlet 13, and the reagent is injected into the reagent inlet 16. Thus, the blood sample and the reagent are respectively imported into the sample channel 14 and the reagent channel 17 by the centrifugal force.
One end of the sample channel 14 is connected with the sample inlet 13 at the geometric center of the channel body 1 and another end extends outwardly in a spiral manner to form an arc-shaped structure surrounding the sample inlet 13. The sample channel 14 is disposed within the channel body 1. In the embodiment, an isolation tank 15 is disposed within the channel body 1. The isolation tank 15 is adjacent to the sample channel 14 and communicates with the sample channel 14. The isolation tank 15 can be same with the sample channel 14 that is the arc-shaped structure to surround the sample inlet 13. In the embodiment, the design that a part of the sample channel 14 extends outwardly can be utilized to communicate the isolation tank 15, so that the middle area of the sample channel 14 communicates with the isolation tank 15. Specifically, the whole structure of the sample channel 14 together with the isolation tank 15 presents a form of non-uniform width that its two ends is narrower and its center is wider, namely, the area adjacent to the sample inlet 13 and the mixing channel 18 is narrower and the center area is wider due to arrangement of isolation tank 15. Lighter cells in blood samples can be isolated from the isolation tank 14 and the sample channel 15. Details will be described in following paragraphs.
Similarly, the reagent channel 17 can be an arc-shaped structure to surround the reagent inlet 16. One end of mixing channel 18 of the embodiment further has a confluence point 181 connected with the sample channel 14 and the reagent channel 17. The isolated blood sample and the reagent can flow together at the confluence point and then flow into the mixing channel 18. Another end of the mixing channel 18 communicates with the collecting unit 2. Thus, the mixing solution of the blood sample and the reagent can flow into the collecting unit 2. Other details will be described in the following paragraphs.
The isolation tank 15 is utilized for receiving density gradient solutions. In the embodiment, it takes the isolation of the circulating tumor cells from the blood sample. The density gradient solution should be injected into the isolation tank 15 before injected into the blood sample. When the channel body 1 is driven to rotate, the density gradient solution forms a density gradient in the isolation tank 15 so as to sieve cells of different weights in the blood sample by the density gradient.
When the blood sample flows through the confluence area of the sample channel 14 and the isolation tank 15, the blood sample is filtered by the centrifugal force and the density gradient solution. The light cells LC or molecular are suspended in the low density area A and flow to the mixing channel 18 by the centrifugal force. The heavy cells or molecular HC flow to the high density area B. Briefly, the flow path of the blood sample is started at the sample inlet 13, and then flows along the sample channel 14. The light cells LC flow to the mixing channel 18 by the centrifugal force and the heavy cells HC are stopped at the high density area B by filtering effect resulting from the centrifugal force and the density gradient. Thus, the light cells LC and the heavy cells HC can be separated. The blood sample in the mixing channel 18 only includes light cells LC (including circulating tumor cells) and other small molecules. After the isolated blood sample flows through the mixing channel 18, the isolated blood sample flows into the collecting unit 2. Therefore, the circulating tumor cells in the blood sample are isolated and collected.
In addition, after the reagent is injected via the reagent inlet 16, the reagent flows into the reagent channel 17 and then flows into the mixing channel 18 by the centrifugation force. The reagent can be mixed with the isolated blood sample. The reagent can be a buffer solution or a solution having labeling materials for circulating tumor cells (i.e., detect a target). The solution having labeling materials for circulating tumor cells can be fluorescent dye, antibody, immuno-marker or magnetic bead. The circulating tumor cells can be labeled in the mixing channel 18 and then flow into the collecting unit 2. The circulating tumor cells can also be labeled in the collecting unit 2. Thus, detection of content of circulating tumor cells from the blood sample can be achieved.
Referring to
Preferably, as shown in
The channel body 1, the collecting unit 2 and the waste liquid tank 3 can include varieties of different implementations. Advanced descriptions are as following embodiment.
Additionally,
The collecting units 2 (2a, 2b) of above embodiments are disposed in the channel body 1 (1a, 1b) in a planar manner. In the other embodiment, the collecting units 2 (2a, 2b) can be disposed in the channel body 1, 1a, 1b in a vertical manner.
As shown in
In addition, referring to
Please refer to
In addition, a centrifugal channel device is further provided in the present invention. The centrifugal channel device includes a channel body, at least one collecting unit and a waste liquid tank. The channel body includes a first surface and a second surface relatively disposed. The channel body includes a sample channel, a reagent channel and a mixing channel. The relationship of connection between the sample inlet, isolation tank, reagent inlet and other components are same as that of above embodiment, which can directly refer to the channel body 1 of the first embodiment. When the overflow hole of the collecting unit is disposed on the second surface, the waste liquid tank is connected with the second surface of the channel body (same as the first embodiment), and when the overflow hole of the collecting unit is disposed on the exterior of the channel body, the waste liquid tank is connected to the exterior of the channel body as shown in the fourth embodiment. Thus, the relationship of the collecting unit and the waste liquid tank can refer to the centrifugal channel device C4 of the fourth embodiment and they are not repeated again.
Additional centrifugal channel device is further provided in the present invention. The centrifugal channel device includes a channel body, at least one collecting unit and a waste liquid tank. The channel body includes a first surface and a second surface relatively disposed. The channel body includes a sample inlet, at least one sample channel, an isolation tank, a reagent inlet, at least one reagent channel, at least one mixing channel and at least one first connection part. The sample inlet is disposed on the first surface. The sample channel is connected with the sample inlet. The isolation tank is disposed adjacent to the sample channel and communicates with the sample channel. The reagent inlet is disposed on the first surface. The reagent channel is connected with the reagent inlet. One end of the mixing channel is connected with the sample channel and the reagent channel. The first connection part is disposed on the second surface. The waste liquid tank is detachably disposed within the channel body. The waste liquid tank includes at least one second connection part. The first connection part and the second connection part cooperate with each other. The collecting unit includes an opening and at least one overflow hole. The opening communicates with another end of the mixing channel. The overflow hole communicates with the waste liquid tank.
The sample inlet, the sample channel, the isolation tank, the reagent inlet, the reagent channel and the mixing channel can be referred to above embodiments. In the embodiment, the second surface of the channel body has a first connection part. The waste liquid tank includes a second connection part. The first connection part and the second connection part cooperate with each other, for instance, the first connection part can be a hook and the second connection part can be a slot. Thus, the first connection part and the second connection part can be referred to the centrifugal channel device C7 of the seventh embodiment. The relationship and the configuration of the other units can be referred to the centrifugal channel device C4 of the fourth embodiment and they are not repeated again.
Referring to
During disposition, the channel body 1g (disk) is slantingly inserted to the accommodation space P of the waste liquid tank 3h, and then it is disposed at the waste liquid tank 3h by the fixing element S. The fixing element S may be for example but not limited to a screw, a pin or a nail.
The channel body 1g (disk) and the waste liquid tank 3h are disposed separately. Thus, it is possible to apply the waste liquid tank 3h to different channel body 1g (disk), and to reuse. The waste liquid tank 3h may be reused under acceptable capacity condition for reducing cost. Besides, if the thickness of the channel body 1g (disk) changes, it is still possible to apply the waste liquid tank 3h to the channel body 1g (disk) which has different thickness and different channel configuration.
The channel body 1g is formed by combining two disks. The above mentioned channel is recessed on one of the two disks and covered by the other disk to form the channel. Or from the sectional view of the channel, regarding the channel for constituting the sample channel, the reagent channel and the mixing channel, its one part is recessed on one of the two disks and the other part is recessed on the other one of the two disks. The two disks are attached to each other to form the channel. Because other element relationships or variations can refer to the previous embodiment, they are not repeated here.
The channel board CB includes a sample inlet 13h and at least one reagent inlet 16h. In the embodiment, there are three reagent inlets 16h for example. Besides, a sample channel, at least one reagent channel and at least one mixing channel may be recessed on the channel board CB, and they are covered with the cover plate CP or the bottom plate BP to form the channel (because these channels can refer to the previous embodiment, they are not repeated here). Or from the sectional view of the channel, regarding the channel for constituting the sample channel, the reagent channel and the mixing channel, its one part is recessed on one of the channel board CB and the other part is recessed on the cover plate CP or the bottom plate BP. The channel board CB is covered with the cover plate CP or the bottom plate BP to form the channel. Because other element relationships or variations can refer to the previous embodiment, they are not repeated here.
In the embodiment, the waste liquid tank 3i is disposed at the bottom plate BP for reducing the cost of processing the waste liquid and avoiding pollution on system due to the waste liquid.
In summary, the centrifugal channel device of the present invention utilizes the flow channel design (especially the relationship between the sample flow channel configuration and isolation tank) to select cells in the sample by the centrifugal force and filtering of the density gradient solution when the sample is flowed through the confluence area of the sample channel and the isolation tank. Thus, the lighter cells or molecular can be flowed into the mixing channel by centrifugal force and the heaver cells can be flowed into the isolation tank for separating the substances of the sample.
Additionally, because the waste liquid tank communicates with the overflow hole of the collecting unit, the waste liquid tank can undertake the excessive sample. Thus a large number of the samples can be easily processed, and the overall clean of the centrifugal channel device can be maintained accordingly and the contamination can be avoided.
Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternative embodiments, will be apparent to persons skilled in the art. It is, therefore, contemplated that the appended claims will cover all modifications that fall within the true scope of the invention.
Number | Date | Country | Kind |
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104100781 A | Jan 2015 | TW | national |
Number | Name | Date | Kind |
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3864089 | Tiffany | Feb 1975 | A |
Number | Date | Country |
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I363871 | May 2012 | TW |
201332661 | Aug 2013 | TW |
Number | Date | Country | |
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20160199836 A1 | Jul 2016 | US |