TWM590971U - Microchannel structure, chip and system - Google Patents

Abstract

This creation provides a micro-channel structure for removing circulating tumor cells in the blood, including: a blood sample inlet for the blood sample to enter; a bead system retention section with a first end and a second end, where the first end and the blood The sample inlet is connected; the bead blocking surface located in the bead system retention section and adjacent to the second end, wherein the bead system retention section defines channels at both ends of the bead blocking surface for the circulation of the processed blood sample, and The bead blocking surface and the first end enable a plurality of beads to form a bead array in the bead system retention section; and a blood sample outlet connected to the second end of the bead system retention section.

Description

Micro-channel structure, chip and system

This work is about a micro-channel structure, chip and system for removing circulating tumor cells in blood, especially a micro-channel structure, chip and system for removing blood tumor cells in blood.

The high mortality rate caused by cancer in recent years has been a serious threat to human life. The study found that most of the early tumors were organ-limited diseases, but in the later stage, they almost spread to the distant organs through the bloodstream to form metastases. This remote metastasis is often the main reason for the death of patients. Cells that detach from the primary site of the tumor and further enter the blood circulation system are called circulating tumor cells. Circulating tumor cells are considered to be one of the important causes of distant tumor metastasis. The expression of the markers is an important indicator for the judgment of cancer patients after recovery and the evaluation of curative effect.

However, in the prior art, the device for detecting and collecting circulating tumor cells has the defects of low detection rate and low collection purity, and the used sample cannot be reused (for example, returned to the individual). Therefore, there is an urgent need for a low-cost, high sensitivity, high specificity, high efficiency, and high convenience system and method to detect and Remove circulating tumor cells.

The reason for this is that the applicant, in view of the lack of conventional technology, after careful experiment and research, and a persevering spirit, finally created this case "micro-channel structure, chip and system" to improve the above-mentioned conventional technology Missing.

This creation is a micro-channel chip with the function of detecting and removing rare cells in blood. The micro-channel chip uses a transparent bead system to stay in the micro-channel chip and form a special bead array to reduce the blood sample in the micro-channel The flow rate in the flow channel chip can more efficiently grasp the rare cells circulating in the blood, especially the cells with carcinogenic or cancerous characteristics (such as circulating tumor cells), and collect the conventional blood cells other than the rare cells and can collect Return the individual. The system and device described in this work can be used for cancer adjuvant therapy, blood bag dialysis, blood immunotherapy and metastatic cancer cell therapy.

One aspect of this creation is to provide a micro-channel system for removing circulating tumor cells in blood, including: a sample area to be processed to provide a blood sample; a micro-channel chip and the sample area to be processed Connected to process the blood sample, the micro-channel chip has a micro-channel structure, the micro-channel structure includes: a blood sample inlet for the blood sample to enter; a bead system retention section with a first End and a second end, wherein the first end is connected to the blood sample inlet; a bead blocking surface is provided in the bead system retention section and is adjacent to the second end, wherein the bead system retention section is at The two ends of the bead blocking surface define a channel for the processed blood sample to circulate, and the bead blocking surface and the first end allow a plurality of beads to form a bead in the bead system retention section Body array; and a blood sample outlet, and the The second end of the bead system remaining section is connected; and a pump is connected to the micro-channel chip to generate a negative pressure for the blood sample to flow in the micro-channel structure.

Another aspect of this creation is to provide a micro-channel structure for removing circulating tumor cells in the blood, including: a blood sample inlet for a blood sample to enter; a bead system retention section with a first end and A second end, wherein the first end is connected to the blood sample inlet; a bead blocking surface is provided in the bead system retention section and is adjacent to the second end, wherein the bead system retention section is in the bead A channel is defined at both ends of the body blocking surface for the processed blood sample to circulate, and the bead blocking surface and the first end form a plurality of beads in the bead system retention section to form a bead array And a blood sample outlet connected to the second end of the bead system retention section.

Another aspect of this creation is to provide a micro-channel structure for removing circulating tumor cells in the blood, including: a blood sample inlet for a blood sample to enter; a bead system retention section with a first end and A second end, wherein the first end is connected to the blood sample inlet, and the bead system retention section includes: a first zone that cooperates with the first end to make a plurality of beads in the bead system retention section Forming a bead array; and a second area adjacent to the second end for smooth circulation of the processed blood sample; and a blood sample outlet connected to the second end of the remaining section of the bead system.

Another aspect of this creation is to provide a micro-channel chip that removes circulating tumor cells in the blood, including only one micro-channel structure of this creation.

Another aspect of this creation is to provide a micro-channel chip for removing circulating tumor cells in the blood, including a plurality of micro-channel structures in this creation.

In order to make the above-mentioned and other purposes, features and advantages of this creation more obvious and understandable, the following is a preferred embodiment, in conjunction with the accompanying drawings, for a detailed description.

10‧‧‧Micro channel system

20‧‧‧Pending sample area

30‧‧‧Microchannel chip

40‧‧‧Pump

50‧‧‧Processed sample area

60‧‧‧Pearl

70‧‧‧Pearl array

310‧‧‧ substrate

320‧‧‧Body

321‧‧‧First surface

322‧‧‧Second surface

330‧‧‧Micro channel structure

410‧‧‧ blood sample entrance

420‧‧‧Expansion section

430‧‧‧Increase resistance section

440‧‧‧ Pearl system retention section

441‧‧‧The first end

442‧‧‧Second end

443‧‧‧District 1

444‧‧‧District 2

450‧‧‧ Slow flow section

460‧‧‧Export of blood samples

470‧‧‧Pearl block structure

471‧‧‧entry side

472‧‧‧Bulging out the center

473‧‧‧Pearl blocking surface

474‧‧‧First side

475‧‧‧Second side end

476‧‧‧The first side

477‧‧‧Second output side end

478‧‧‧buffer surface

479‧‧‧channel

500‧‧‧Microchannel chip

Figure 1 is a schematic diagram of the creation micro-channel system;

Figure 2 is a schematic top view of the microchannel chip created;

Figure 3 is a schematic longitudinal cross-sectional view of A-A' in Figure 2;

Figure 4 is a schematic plan view of the remaining section of the bead system of the creation;

Figure 5 is a schematic top view of the creation of beads in the bead system to form a bead array;

Figure 6 is a schematic diagram of creating a micro-channel chip by combining multiple micro-channel structures;

Figure 7 is the result graph of the circulating tumor cell grasping rate and blood cell survival rate of the created micro-channel system under different negative pressures; and

Figure 8 is a graph showing the effect of different concentrations of antibody labeled on beads on the efficiency of capturing circulating tumor cells.

The following describes the embodiments of the "micro-channel structure, chip and system" in this case, please refer to the drawings, but the actual configuration and the method adopted do not necessarily fully conform to the content described, and those skilled in the art Various changes and modifications can be made without departing from the actual spirit and scope of the case.

Please refer to Figure 1, which is a schematic diagram of the micro-channel system created by the author. The microchannel system 10 of the present invention includes a sample area 20 to be processed, a microchannel wafer 30 provided with beads, a pump 40, and a processed sample area 50. The to-be-processed sample area 20 is used to provide blood samples. The to-be-processed sample area 20 may be a storage device for storing blood samples, such as a blood collection tube or a blood bag, or may be a pipeline connected from a human blood vessel to separate blood from the body The sample is guided to the microchannel wafer 30. The processed sample area 50 is used to recover processed blood samples. The processed sample area 50 may be a storage device for recovering blood samples, such as a blood collection tube or a blood bag, or a pipeline connected from a blood vessel of the human body. The blood sample in the place is led back to the human blood vessel. The pump 40 can make the sample region 20 to be processed and the micro-channel wafer 30 under a negative pressure state, so that the blood sample flows in the micro-channel wafer 30. The pump 40 of this creation can be disposed between the micro-channel wafer 30 and the processed sample area 50, so that the processed blood sample flows out of the micro-channel wafer 30, and then flows through the pump 40 and then to the processed sample area 50. The pump 40 of the present invention may also be disposed after the processed sample area 50, so that the processed blood sample flows out of the micro-channel wafer 30 and then flows to the processed sample area 50. The pump 40 of this creation may be a pump such as an air pump, a vacuum pump, a peristaltic pump, etc., which may cause the micro-channel chip 30 to be in a negative pressure state.

Please refer to Figures 2~3, which are a schematic top view of the micro-channel wafer created and a longitudinal cross-sectional view along A-A'. The micro-channel wafer 30 of the present invention includes a substrate 310, a body 320 and a micro-channel structure 330. The body 320 has a first surface 321 and a second surface 322 opposite to the first surface 321. The micro-channel structure 330 is embedded in the second surface 322 of the body 320, and the second surface 322 will closely cover the substrate 310 , The micro-channel structure 330 forms a micro-channel between the body 320 and the substrate 310.

The microchannel structure 330 of the present invention includes a blood sample inlet 410, an expansion section 420, a resistance increasing section 430, a bead system retention section 440, a slow flow section 450, and a blood sample outlet 460 in order from the inlet to the outlet. The blood sample inlet 410 of the present invention extends from the first surface 321 to the second surface 322 of the body 320, and can be connected to a tube connected to a blood collection tube, a blood bag, or a human blood vessel, so that the blood sample enters the microchannel. The blood sample inlet 410 may be a round hole or a polygonal hole, preferably a round hole. The diameter of the blood sample inlet 410 of this creation is 1.5 mm.

The expansion section 420 of this creation is connected to the blood sample inlet 410, and may be circular or polygonal, preferably square. The expansion section 420 can buffer the blood sample with a rapid flow rate, and at the same time prevent the blood sample from leaking due to excessive hydraulic pressure. The width of the expansion section 420 of this creation is 1.5 mm, and the depth is between 0.2 and 1.5 mm.

The resistance-increasing section 430 and the extension section 420 of this creation may be round or polygonal, preferably square, and the width of the resistance-increasing section 430 will be smaller than the width of the extension section 420 and the blood sample inlet 410, and The particle size is larger than that of the bead, so that the fluid resistance can be enhanced while the bead passes, and the function of preventing the blood sample from bursting and limiting the flow of the blood sample is prevented. The resistance-increasing section 430 of this creation has a width of 0.3 mm and a depth of 0.2 mm.

Please refer to Fig. 4, which is a schematic top view of the remaining section of the bead system created for this. The bead system retention section 440 of the present invention has a first end 441 and a second end 442, wherein the first end 441 is connected to the resistance increasing section 430, and the second end 442 is connected to the slow flow section 450, the bead system retention area Section 440 may retain the beads 60 in this section (as shown in Figure 5).

The first end 441 of the bead-retaining section 440 may have various shapes, such as Linear shape, arc shape, multi-curved shape, etc., wherein the arc shape is the preferred embodiment, which can make the blood sample more dispersed in this section and flow through the gap between the beads 60.

In the bead system stay section 440 and near the second end 442, a bead block structure 470 is provided. The bead block structure 470 has an entrance side 471 and a central convex side 472, and the entrance side 471 is convex relative to the center The side 472 is closer to the side of the first end 441 of the bead retention zone 440, and the central convex side 472 is the side closer to the second end 442 of the bead retention zone 440 relative to the entry side 471. The entrance side 471 is a bead blocking surface 473, which is the barrier wall of the bead 60 in the bead system retention section 440, so that the bead 60 forms the bead array 70 in the bead system retention section 440. This part Leave the first zone 443 of the section 440 for the bead system (as shown in Figure 5). The bead blocking surface 473 has a first side end 474 and a second side end 475, the central convex side 472 has a first side end 476 and a second side end 477, and the first side end 474 extends to the first side End 476, and the second side end 475 extends to the second output side end 477 to form a buffer surface 478 respectively, and two channels 479 are formed between the two buffer surfaces 478 and the second end 442, so that the blood sample is processed The two channels 479 circulate smoothly and flow to the slow flow section 450, which is the second zone 444 of the bead retention section 440 (as shown in FIG. 5).

The width of the remaining section 440 of the bead system of the present invention will affect the flow rate of the blood sample in the micro-channel structure 330, and the difference in flow rate will also affect the grasping efficiency of circulating tumor cells, where the greater the width, the better the grasping efficiency. The depth of the remaining section 440 of the bead system of the present creation may be greater than the particle size of the bead 60. The width of the staying section 440 of the bead system of this creation is between 0.3~4.8mm, and the depth is between 0.08~1.5mm. In order to retain the bead 60 in the bead system retention section 440 to form the bead array 70, two channels The pore size of 479 needs to be smaller than the particle size of the bead 60, so that the bead 60 cannot enter the two channels 479. The depth of the two channels 479 in this creation is less than 0.05mm.

The bead system retention section 440 of the present creation can accommodate 100 to 500 beads 60 to form a bead array 70. The bead array 70 can effectively make the blood sample achieve a constant or slow effect in the gap between the beads 60. This effect can reduce the mortality of blood cells, and the efficiency of the beads 60 to grab circulating tumor cells Significantly improved. The two channels 479 of the reserved section 440 of the bead system of the present invention can make the blood sample have more routes to flow in the bead array 70, so as to achieve the effect of constant speed or slow speed, and then avoid the cells passing through the bead slit , There will be a constant rate of white effort movement in the fluid. This movement will cause the cells in the slit to speed up. This situation will cause the cells to generate pressure and cause cell damage. The time to contact the beads decreases.

The size of the beads in this creation is between 10~200μm. The beads are made of biocompatible plastic materials. The surface of the bead is covered with biomarkers that can grab circulating tumor cells. The biomarker can be any marker that can grab the rare cells in the blood, including biomarkers such as antibodies, aptamers, short-chain peptides or sugars. The biomarkers created in this book are all equipped with Biotin, and the streptavidin is adhered to the beads. The biotin on the biomarkers will be combined with the biostreptomycin on the beads to ensure that The reactive substances on the biomarkers on the beads all face outwards to better capture the rare cells in the blood sample. For example, when the biomarker is an antibody, biotin will be marked at the bottom of the heavy chain (ie, the carboxyl end of the heavy chain), so when the biotin on the antibody binds to the streptomycin on the bead, the antibody carries a reaction One end of a substance (such as EpCAM) It will face the blood sample and grab the rare cells (such as circulating tumor cells) in the blood sample with the greatest probability.

Please continue to refer to Figures 2~3. The slow flow section 450 of the present invention is connected to the second end 442 of the bead retention section 440, and may be circular or polygonal, preferably square. The pore size of the slow flow section 450 is smaller than the particle diameter of the bead 60, and has a repeated bending structure to stabilize the flow velocity of the blood sample in the micro-channel structure 330. The width of the slow flow section 450 of this creation is 0.2 mm, and the depth is less than 0.05 mm.

The blood sample outlet 460 of the present creation is connected to the slow flow section 450 and extends from the second surface 322 of the body 320 to the first surface 321. The processed blood sample will flow from the blood sample outlet 460 to the pump 40 or the processed sample area 50 (as shown in Figure 1) for the subsequent return to the individual. The blood sample outlet 460 may be a circular hole or a polygonal hole, preferably a circular hole. The diameter of the blood sample outlet 460 of this creation is 1.5 mm.

Another embodiment of the present invention is that multiple micro-channel structures 330 can be combined into one micro-channel wafer 500, as shown in FIG. 6. The micro-channel wafer 500 may have various shapes, preferably a disk shape, and each micro-channel structure 330 is disposed in the micro-channel wafer 500 in a radial manner. In other words, multiple micro-channel structures 330 share the same blood sample inlet 410, and the blood sample inlet 410 is located at or near the center of the micro-channel wafer 500, and the remaining sections of the micro-channel structure 330 are gradually oriented The micro-channel wafer 500 is provided around. In the micro-channel wafer 500 of this embodiment, after the blood sample is injected from the blood sample inlet 410, it will be evenly distributed into each micro-channel structure 330, so that a larger amount of blood samples can be analyzed in a short time to achieve high Flux (High through put). Since the content of circulating tumor cells in the blood is generally low in the early stage of cancer, the concept of adding high-throughput to the microchannel chip in the whole blood test can analyze only one microflow at a fixed time than the original The wafer of the channel structure has a larger amount of blood. In one embodiment, the radius of the micro-channel wafer 500 is 4 cm, and the number of micro-channel structures 330 in the micro-channel wafer 500 is 2-8.

The material of the substrate 310 of this creation can be acrylic (polymethylmethacrylate, PMMA), polyethylene terephthalate (PET), polycarbonate (PC), polydimethyl siloxane ( polydimethylsilicon (PDMS), silicone, rubber, plastic or glass. The material of the body 320 may be polymethylmethacrylate (PMMA), polyethylene terephthalate (PET), polycarbonate (PC), polydimethylsilicon (PDMS) ), silicone, rubber or plastic. When selecting materials for the substrate 310 and the body 320, the material characteristics between the substrate 310 and the body 320 must be considered. Both the substrate 310 and the body 320 of this creation have the effect of transmitting light, so they can be observed with all optical instruments.

The preparation method of the micro-channel wafer created in this creation is to first print the master mold using a 3D printer. The master mold is a photo-curable resin that is rinsed with 95% alcohol. After UV light curing for 2 minutes, it is rinsed with alcohol again and placed in an oven to dry. Bake for 10 minutes. After the food-grade material PDMS liquid is poured into the master mold in proportion, after a 50-minute 80-degree curing step, an oxygen plasma machine is used to join the glass substrate. Finally, place the labeled biomarker beads into the microchannel chip, and then connect the blood sample inlet to the sample area to be processed, and The blood sample outlet is connected to the pump or the sample area to be processed to obtain the micro-channel system of the original creation.

Experimental example

Negative pressure conditions are related to circulating tumor cell capture efficiency and blood cell survival rate

The pump of this creation uses the vacuum driving method to make the micro-channel structure in a negative pressure state, so that the circulating tumor cells in the blood are caught on the beads, and the blood sample flows in the micro-channel chip. Different vacuum degrees are related to the circulating tumor cell grasping efficiency and blood cell survival rate, and the higher the vacuum degree, the higher the negative pressure in the microchannel structure, resulting in a faster blood sample flow rate in the microchannel structure. Please refer to Figure 7, which is the result graph of the micro-channel system created under different negative pressures, the circulating tumor cell grasping rate and blood cell survival rate. The results in Figure 7 show that the grabbing rate of circulating tumor cells in a low negative pressure state is higher than that in a high negative pressure state, and the survival rate of blood cells in a low negative pressure state is higher than that in a high negative pressure state. Survival rate under negative pressure, and the best grasping rate and highest survival rate under 5~10-Kpa negative pressure state. Therefore, when the flow rate is lower, the viability of blood cells is higher, and the effect of grabbing circulating tumor cells is better.

Detection sensitivity of micro-channel system

In this creation, 10, 20, 30, 50 and 100 spiked cancer cells of different numbers were added to 2000 μL of blood, respectively, to observe the detection sensitivity of the microchannel system and observe the survival rate of blood cells. As shown in Table 1. It can be seen from Table 1 that even if there are only 10 spiked cancer cells in 2000 μL of blood, the microfluidic system of this author can still capture the spiked cancer cells, and the survival rate of blood cells is 100%. Therefore, the original The detection sensitivity of the micro-channel system is high, and can maintain the survival of blood cells.

The relationship between the concentration of biomarkers and the efficiency of beads to capture circulating tumor cells

After the antibody is labeled with fluorescent light, 2nmol, 3nmol, 6nmol, 12nmol and 18nmol antibodies are labeled on the beads, and the beads are placed in the microchannel chip to observe the different concentrations of antibodies labeled on the beads The effect on the efficiency of capturing circulating tumor cells in vivo is shown in Figure 8. In Figure 8, the x-axis is the antibody concentration, and the y-axis is the fluorescence intensity relative to when there is no fluorescence. It can be clearly seen from Figure 8 that when the antibody concentration is 2nmol, the beads can effectively grab the circulating tumor cells, and when the antibody concentration reaches 6nmol, the beads can grab the circulating tumor cells with the best effect . Therefore, when the concentration of biomarkers is 2-6 nmol, the beads can effectively grab circulating tumor cells.

The actual test results of the micro-channel system

The blood sample with MCF-7 cancer cells was actually infected with MCF-7 cancer cells using live cell dye CaAM (Calcein Acetoxymethylester) and DNA cross-linking dye hoechst, and then flowed through the micro-channel system created by the author. The actual blood test After body staining, the image of the micro-channel system created by the author (please refer to Figures 1~3), where Figure 1 is the image of the micro-channel system under an optical microscope, and Figures 2~3 are fluorescent Image of the micro-channel system under the microscope. It can be seen from Figure 2 that the bead grabs the location of MCF-7 cancer cells (green fluorescent spot), and from Figure 3 that it can be seen that the DNA of MCF-7 cancer cells is stained by the DNA cross-linking agent hoechst Location (blue fluorescent place). Therefore, as can be seen from FIGS. 2 to 3, the positions of the green fluorescence and the blue fluorescence are the same, so it can be confirmed that after the blood sample passes through the special bead array, the beads can indeed grab the cancer cells.

Other embodiments

1. A micro-channel system for removing circulating tumor cells in blood, comprising: a sample area to be processed to provide a blood sample; and a micro-channel chip connected to the sample area to be processed for processing For the blood sample, the micro-channel chip has a micro-channel structure, the micro-channel structure includes: a blood sample inlet for the blood sample to enter; a bead system retention section with a first end and a second End, wherein the first end is connected to the blood sample inlet; a bead blocking surface is provided in the bead system retention section and is adjacent to the second end, wherein the bead system retention section is on the bead blocking surface The two ends of each define a channel for the processed blood sample to circulate, and the bead blocking surface and the first end allow a plurality of beads to form a bead array in the bead system retention section; and a The blood sample outlet is connected to the second end of the remaining section of the bead system; and a pump is connected to the microchannel chip to generate a negative pressure to flow the blood sample in the microchannel structure.

2. The micro-channel system as described in embodiment 1, wherein the pump includes a Pumping pump, a vacuum pump or a peristaltic pump.

3. The micro-channel system according to embodiment 1 or 2, further comprising a processed sample area, connected to the blood sample outlet or the pump, for recovering the processed blood sample.

4. A micro-channel structure for removing circulating tumor cells in blood, comprising: a blood sample inlet for a blood sample to enter; a bead system retention section with a first end and a second end, wherein The first end is connected to the blood sample inlet; a bead blocking surface is provided in the bead system retention section and is adjacent to the second end, wherein the bead retention section is at both ends of the bead blocking surface Each defines a channel for the processed blood sample to circulate, and the bead blocking surface and the first end allow a plurality of beads to form a bead array in the bead system retention section; and a blood sample outlet , Connected to the second end of the remaining section of the bead system.

5. The micro-channel structure as described in embodiment 4, wherein each bead has a particle size, each of the channels has a pore size, and the pore size is smaller than the particle size, so that each bead system remains in the bead system In the remaining section, and on the surface of each bead, there are a plurality of antibodies for grabbing circulating tumor cells in the blood sample, and the bead array reduces the flow rate of the blood sample in the gap of the bead array .

6. The micro-channel structure according to embodiment 4 or 5, further comprising a bead blocking structure, wherein the bead blocking structure includes: an entrance side, relatively close to the first end, having a first side end and A second side end, which is the blocking surface of the bead; a central convex side, relatively close to the second end, and having a first out side end and a second out side end; and two buffer surfaces, Extend from the first and second side ends to the first One and the second outlet side end, forming the two channels for the smooth circulation of the processed blood sample with the second end.

7. The micro-channel structure as described in any one of embodiments 4-6, further comprising a resistance increasing section and a slow flow section, wherein the resistance increasing section is disposed at the blood sample inlet and the bead Between the first end of the system retention section, the slow flow section is disposed between the second end of the bead system retention section and the blood sample outlet, and the resistance increasing section and the slow flow section It is used to reduce the flow rate of the blood sample in the remaining section of the bead system.

8. A micro-channel structure for removing circulating tumor cells in blood, comprising: a blood sample inlet for a blood sample to enter; a bead system retention section with a first end and a second end, wherein The first end is connected to the blood sample inlet, and the bead system retention section includes: a first zone that cooperates with the first end to form a plurality of beads in the bead system retention section And a second zone adjacent to the second end for smooth circulation of the processed blood sample; and a blood sample outlet connected to the second end of the bead system retention section.

9. A micro-channel chip for removing circulating tumor cells in blood, comprising only one micro-channel structure as described in any one of embodiments 4-8.

10. A micro-channel chip for removing circulating tumor cells in blood, comprising a plurality of micro-channel structures as described in any one of embodiments 4-8.

11. The micro-channel wafer as described in embodiment 10, wherein the plurality of micro-channel structures are arranged in the micro-channel wafer in a radial manner.

12. The micro-channel wafer according to embodiment 10 or 11, wherein each micro-channel The flow channel structure shares the same blood sample inlet, and the blood sample inlet is located at the substantially central position of the microchannel wafer.

13. The micro-channel wafer as described in any one of embodiments 10-12, wherein the micro-channel wafer is disk-shaped, and the number of the plurality of micro-channel structures is 2-8.

Based on the above, in this work, an antibody with a biomarker that can identify circulating tumor cells is labeled on the beads, and then the beads are placed in the micro-channel structure to obtain a micro-channel chip. Flowing blood samples through the microchannel chip created in this book can not only improve the sensitivity of grabbing the rare circulating tumor cells in the blood, but also improve the efficiency of the beads to grab the circulating tumor cells without causing damage to the blood cells and improve the survival of the blood cells. In order to further use the blood sample with the circulating tumor cells removed for more purposes, for example, to return the blood sample with the circulating tumor cells back to the individual, so that the microfluidic chip created can be used for adjuvant cancer treatment, Blood bag dialysis, blood immunotherapy and metastatic cancer cell treatment are related uses.

440‧‧‧ Pearl system retention section

441‧‧‧The first end

442‧‧‧Second end

470‧‧‧Pearl block structure

471‧‧‧entry side

472‧‧‧Bulging out the center

473‧‧‧Pearl blocking surface

474‧‧‧First side

475‧‧‧Second side end

476‧‧‧The first side

477‧‧‧Second output side end

478‧‧‧buffer surface

479‧‧‧channel

Claims (14)

A micro-channel system for removing circulating tumor cells from blood, including: A sample area to be processed to provide a blood sample; A micro-channel wafer is connected to the sample area to be processed for processing the blood sample. The micro-channel wafer has a micro-channel structure. The micro-channel structure includes: A blood sample inlet for the blood sample to enter; A bead system retention section with a first end and a second end, wherein the first end is connected to the blood sample inlet; A bead blocking surface is provided in the bead retention section and is adjacent to the second end, wherein the bead retention section defines a channel at each end of the bead blocking surface for the treated Blood samples flow, and the bead blocking surface and the first end cause a plurality of beads to form a bead array in the bead system retention section; and A blood sample outlet connected to the second end of the remaining section of the bead system; and A pump is connected to the microchannel chip to generate a negative pressure to flow the blood sample in the microchannel structure. The micro-channel system as described in item 1 of the patent application scope, wherein the pump includes a suction pump, a vacuum pump or a peristaltic pump. The micro-channel system as described in item 1 of the patent application scope further includes a processed sample area connected to the blood sample outlet or the pump for recovering the processed blood sample. A micro-channel structure for removing circulating tumor cells in blood, including: A blood sample entrance for a blood sample to enter; A bead system retention section with a first end and a second end, wherein the first end is connected to the blood sample inlet; A bead blocking surface is provided in the bead retention section and is adjacent to the second end, wherein the bead retention section defines a channel at each end of the bead blocking surface for the treated Blood samples flow, and the bead blocking surface and the first end cause a plurality of beads to form a bead array in the bead system retention section; and A blood sample outlet is connected to the second end of the remaining section of the bead system. The micro-channel structure as described in item 4 of the patent application, wherein each of the beads has a particle size, each of the channels has a pore size, and the pore size is smaller than the particle size, so that each of the bead systems remains on the beads In the system retention section, and on the surface of each bead, there are multiple antibodies for grabbing circulating tumor cells in the blood sample, and the bead array reduces the blood sample in the gap of the bead array Flow rate. The micro-channel structure as described in item 4 of the patent application scope further includes a bead blocking structure, wherein the bead blocking structure includes: An entry side, relatively close to the first end, has a first side end and a second side end, and is the bead blocking surface; A central projecting side, relatively close to the second end, and having a first output side end and a second output side end; and Two buffer surfaces extend from the first and second side ends to the first and second output side ends, respectively, to form the two channels for the smooth circulation of the processed blood sample with the second end. The micro-channel structure as described in item 4 of the patent application scope further includes a resistance increasing section and a slow flow section, wherein the resistance increasing section is provided at the blood sample inlet and the bead system retention section Between the first end, the slow flow section is disposed between the second end of the bead system retention section and the blood sample outlet, and the resistance increasing section and the slow flow section are used to lower the blood sample The flow rate in the remaining zone of the bead system. A micro-channel structure for removing circulating tumor cells in blood, including: A blood sample entrance for a blood sample to enter; A bead system retention section has a first end and a second end, wherein the first end is connected to the blood sample inlet, and the bead system retention section includes: A first zone that cooperates with the first end to form a plurality of beads in the bead system retention section to form a bead array; and A second zone adjacent to the second end for smooth circulation of the processed blood sample; and A blood sample outlet is connected to the second end of the remaining section of the bead system. A micro-channel chip for removing circulating tumor cells in blood only includes a micro-channel structure as described in any of items 4 to 8 of the patent application. A micro-channel chip for removing circulating tumor cells in blood includes a plurality of micro-channel structures as described in any of items 4 to 8 of the patent application. The micro-channel wafer as described in item 10 of the patent application range, wherein the plurality of micro-channel structures are arranged in the micro-channel wafer in a radial manner. The micro-channel wafer as described in item 11 of the patent application range, wherein each micro-channel structure shares the same blood sample inlet, and the blood sample inlet is located at a substantially central position of the micro-channel wafer. The micro-channel wafer as described in item 10 of the patent application range, wherein the micro-channel wafer is disc-shaped. The micro-channel wafer as described in item 10 of the patent application scope, wherein the number of the plurality of micro-channel structures is 2-8.

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