CN210230001U

CN210230001U - Micro flow channel chip and micro flow channel structure

Info

Publication number: CN210230001U
Application number: CN201920350475.1U
Authority: CN
Inventors: Jiuyuan Dong; 董久源; Songqi Cai; 蔡松锜
Original assignee: Laifu Kede Biotechnology Co Ltd
Current assignee: Dong Jiuyuan
Priority date: 2019-03-20
Filing date: 2019-03-20
Publication date: 2020-04-03
Anticipated expiration: 2029-03-20

Abstract

The utility model relates to a miniflow channel chip and miniflow channel structure, the miniflow channel chip includes the miniflow channel structure, just the miniflow channel structure includes: a microfluidic sample inlet for entry of a microfluidic sample; a resistance-increasing section connected to the microfluidic sample inlet; a detection section having a first end and a second end, wherein the first end is connected to the resistance increasing section and is used for inspecting or processing the microfluidic sample, and the bead is disposed in the detection section; and a bead mooring structure coupled to the second end of the detection section. The particle size of the beads is larger than the aperture of the bead mooring structure, so that the beads are moored in the detection section, and a user can conveniently observe the micro-channel structure and the adsorption condition of the beads in the micro-channel chip.

Description

Micro flow channel chip and micro flow channel structure

Technical Field

The present invention relates to a micro flow channel chip and a micro flow channel structure for increasing the capture rate of biological substances, and more particularly to a micro flow channel chip and a micro flow channel structure with a bead-based retention structure, which allow beads to stay in a detection zone statically.

Background

The high mortality rate caused by cancer has been a serious threat to human life in recent years. Researches show that the initial stage of tumorigenesis is organ-localized diseases, but the later stage of tumorigenesis almost spreads to remote organs through blood flow to form metastasis, and the remote metastasis is a main reason which often causes death of patients. The cells that detach from the primary site of the tumor and further enter the blood circulation system are called Circulating Tumor Cells (CTCs), CTCs are considered to be one of the important causes of the occurrence of tumor distant metastasis, and the counting of the number of CTCs and the expression of surface molecular markers of CTCs play important index roles in the judgment and the curative effect evaluation of tumor patients after healing.

According to the change of the tumor itself, the response to chemotherapy and drug treatment, etc., the CTC quantity can be dynamically changed in real time, so that the characteristics can be used for in vitro early diagnosis, rapid evaluation of drugs, individual treatment reference, etc. However, in the blood of cancer patients, CTCs are rare cells, every 10 th⁹The fact that an individual blood cell has only one CTC makes it difficult to detect and isolate CTCs. Therefore, a centralized collection method must be used to efficiently detect and isolate CTCs.

One example of a current focused collection method is the use of highly expressed Cell surface biomarkers with high specificity and sensitivity to CTCs, such as Epithelial Cell Adhesion molecules (EpCAM). Nagrath et al (Nature 2007,450:1235-9) developed anti-EpCAM antibody-based coated microfluidic chips for the detection and collection of CTCs. However, the above techniques have the drawbacks of low detection rate and low collection purity due to the non-specific binding of blood cells to anti-EpCAM antibodies associated with the fluid design structure.

Despite the advances in technologies for detecting and isolating CTCs, there remains a need for more specific and efficient methods for detecting, purifying and releasing CTCs and other biological substances for further breeding and characterization.

Therefore, the applicant has made various experiments and studies to overcome the above-mentioned drawbacks of the prior art and finally developed the "micro flow channel chip with bead-tethered structure and micro flow channel structure" in order to overcome the above-mentioned drawbacks of the prior art.

SUMMERY OF THE UTILITY MODEL

The utility model relates to a novel microfluid system contains the miniflow channel chip and is arranged in the miniflow channel chip and can snatch the pearl body of circulation tumor cell to separate circulation tumor cell from blood cell. The utility model discloses a miniflow channel structure and miniflow channel chip are including increasing resistance district section and pearl body mooring structure very much to in surveying the main district with the pearl body mooring, convenience of customers observes the absorption situation of the pearl body in miniflow channel structure and miniflow channel chip.

The utility model discloses a micro-fluidic system's principle utilizes the characteristic of circulating tumor cell surface antigen and plants and do with the antibody of planting on the pearl surface and snatch, and this pearl body structure leads to the biggest area of contact in the unit volume, and secondly the fluid resistance of miniflow way structure and curved type structure cause the vortex to produce, lead to circulating tumor cell rotation or roll and increase the contact chance with the pearl body and strengthen the effect of snatching, and by the special design of miniflow way structure, reduce the nonspecific combination of blood cell and anti EpCAM antibody.

An aspect of the present invention provides a micro flow channel chip loaded with beads having a particle diameter, including: a substrate; the body is provided with a first surface and a second surface, wherein the second surface is closely covered on the substrate; and a micro-channel structure embedded on the second surface to form a micro-channel between the body and the substrate, wherein the micro-channel structure comprises: a blood sample inlet extending from the first surface to the second surface and having a diameter for blood sample entry; an expansion section connected to the blood sample inlet and having a first width; a resistance increasing section connected with the expanding section and having a second width; the detection section is connected with the resistance increasing section, and the bead body is arranged in the detection section; and a slow flow section connected to the detection section and having a first depth, wherein the particle size is larger than the first depth to prevent the bead from entering the slow flow section, and the second width is smaller than the first width and the diameter to prevent the blood sample from flowing back to the expansion section, thereby retaining the bead in the detection section.

The utility model discloses another aspect provides a load micro-channel structure of pearl body that has particle diameter, including the structure body for make the microfluid sample flow through this micro-channel structure and receive the inspection or handle, wherein this structure body includes: a microfluidic sample inlet having a first aperture for entry of the microfluidic sample; a resistance increasing section connected to the microfluidic sample inlet and having a second aperture; a detection section having a first end and a second end, wherein the first end is connected to the resistance increasing section and is used for detecting or processing the microfluidic sample, and the bead is disposed in the detection section; and a bead mooring structure coupled to the second end for mooring the bead in the detection section.

In order to make the aforementioned and other objects, features and advantages of the present invention comprehensible, preferred embodiments accompanied with figures are described in detail below.

Drawings

FIG. 1 is a schematic top view of a microchannel chip according to the present invention;

FIG. 2 is a schematic longitudinal cross-sectional view taken along line A-A' of FIG. 1;

FIG. 3(A) is a schematic view of beads disposed in a detection section of a micro flow channel chip according to the present invention;

FIG. 3(B) is a schematic view of another embodiment of the micro flow channel chip of the present invention showing beads disposed in the detection section;

FIG. 4 shows the effect of different widths at the second end of the detection section on cell recovery;

FIG. 5 is a schematic view showing that the depth of the slow flow section in the micro flow channel chip is smaller than the bead particle size;

FIG. 6 is a schematic view of a micro flow channel structure according to another embodiment of the present invention;

FIG. 7 is a graph of the recovery efficiency and detection limit of a non-microfluidic system;

FIG. 8 is a graph showing the recovery efficiency and detection limit of the microchannel chip according to the present invention;

FIGS. 9(A) -9(C) are images of the results of separation of blood samples by the microchannel chip of the present invention;

in the drawing, 10 is a micro flow channel chip, 100 is a substrate, 200 is a body, 210 is a first surface, 220 is a second surface, 300 is a micro flow channel structure, 310 is a blood sample inlet, 320 is an expansion section, 321 is a first end, 322 is a second end, 330 is a resistance increasing section, 340 is a detection section, 341 is a first end, 342 is a detection main region, 343 is a second end, 344 is a bead mooring structure, 350 is a slow flow section, 360 is a blood sample outlet, 40 is a bead, 50 is a micro flow channel structure, 500 is a structure body, 510 is a micro flow sample inlet, 520 is a resistance increasing section, 530 is a detection section, 532 is a bead mooring structure, 540 is a slow flow section, 550 is a micro flow sample outlet, and 60 is a bead.

Detailed Description

The following description will be made for each embodiment of the "micro flow channel chip with bead-mooring structure" of the present invention, with reference to the accompanying drawings, but the actual configuration and the method to be carried out do not necessarily completely conform to the description, and those skilled in the art can make various changes and modifications without departing from the actual spirit and scope of the present invention.

The micro flow channel chip of the utility model is loaded with beads, the beads are especially large beads with the particle size of 100-; (2) capturing the bioactive components of the biological substance; or (3) a linking molecule linked to the releasable component and the biologically active component. When the microfluidic sample flows through the bead, the bead can capture biological substances in the microfluidic sample, which can react with the reactive substance on the bead surface, and release the captured biological substances for further research and detection. The material of the beads is transparent plastic or transparent resin. The microfluidic sample may be a body fluid or a bacterial fluid, and the body fluid may include blood, cerebrospinal fluid, various digestive fluids, semen, saliva, sweat, urine, vaginal secretion, or a solution containing a biological substance. Biological substances include CTCs, CTC circulating stem cells (e.g., tumor stem cells, liver stem cells, and bone marrow stem cells), fetal cells, bacteria, viruses, epithelial cells, endothelial cells, or other biological substances. Therefore, the substance applied to the surface of the beads differs for different objects to be grasped.

The embodiment of the utility model provides a separate circulating tumor cells from blood. The micro flow channel chip is internally provided with a plurality of transparent beads, when the beads capture the circulating tumor cells, the circulating tumor cells can be separated from the blood and positioned in the detection section, and the residual normal blood cells can flow out of the outlet and flow into the waste liquid storage tank. For capturing and isolating circulating tumor cells in the blood, the bead surface is preferably coated with an antibody to Epithelial cell adhesion Molecule (EpCAM).

Please refer to fig. 1, 2, 3(a) and 3(B), which are schematic top views and schematic longitudinal cross-sectional views along a-a' of the micro flow channel chip of the present invention. The micro flow channel chip 10 of the present invention includes a substrate 100, a body 200, and a micro flow channel structure 300. The body 200 has a first surface 210 and a second surface 220 opposite to the first surface 210, the micro channel structure 300 is embedded in the second surface 220 of the body 200, and the second surface 220 is covered on the substrate 100 in a sealing manner, so that the micro channel structure 300 forms a micro channel between the body 200 and the substrate 100.

The micro flow channel structure 300 of the present invention comprises a blood sample inlet 310, an expansion section 320, a resistance increasing section 330, a detection section 340, a slow flow section 350 and a blood sample outlet 360 in sequence from the inlet to the outlet.

The blood sample inlet 310 of the present invention extends from the first surface 210 to the second surface 220 of the body 200 for the blood sample to enter the flow channel. The blood sample inlet 310 may be a circular hole or a polygonal hole, preferably a circular hole. The diameter of the blood sample inlet 310 of the present invention is between 0.8-1.2mm, and can accommodate an injector with 18-21G needles (about 0.7-0.9 mm).

The expansion section 320 of the present invention has a first end 321 and a second end 322, the first end 321 is connected to the blood sample inlet 310, and the second end 322 is connected to the resistance-increasing section 330. The aperture of the expansion section 320 may be circular or polygonal, preferably square. The utility model discloses expand the width of district section 320 and be between 0.8-1.5mm, and the degree of depth is 1 mm.

The resistance-increasing section 330 of the present invention has one end connected to the second end 322 of the expanding section 320 and the other end connected to the detecting section 340. The aperture of the resistance-increasing section 330 may be circular or polygonal, preferably square, and the width of the resistance-increasing section 330 is smaller than the width of the expansion section 320 and the blood sample inlet 310 and larger than the particle size of the beads, so that the beads can pass through while the fluid resistance is enhanced, and the function of preventing the liquid from flowing backwards due to the insertion and extraction of the needle is provided. The width of the resistance-increasing section 330 of the utility model is between 250 μm, and the depth is 1 mm. Since the width of the expansion section 320 is greater than the width of the resistance-increasing section 330, the second end 322 of the expansion section 320 can be gradually reduced from the width of the expansion section 320 to the width of the resistance-increasing section 330, i.e. the width of the second end 322 is gradually reduced from 0.8-1.5mm to 250 μm.

The detecting section 340 of the present invention includes a first end 341, a main detecting area 342 and a second end 343, wherein the first end 341 is connected to the resistance increasing section 330, the second end 343 is connected to the slow flow section 350, the main detecting area 342 is located between the first end 341 and the second end 343, and is provided with beads 40 capable of adsorbing the tumor cells circulating in the blood (as shown in fig. 3(a) and 3 (B)). The aperture of the detection section 340 may be circular or polygonal, preferably square. In the embodiment of the present invention, the aperture of the detecting section 340 is square. In order to arrange the beads 40 in the detection main region 342 in a monolayer manner, the detection section 340 is a region for limiting the depth of the flow channel, and the depth of the detection section 340 is 20-50 μm added to the particle size of the beads 40, so the depth of the detection section 340 is between 120 μm and 250 μm. The widths of the first end 341 and the main detection region 342 of the detection section 340 are sufficient for the beads 40 to pass through, and therefore, the widths are between 250 μm and 1.5 mm. The width of the first end 341 of the detection section 340 may be the same as the width of the resistance increasing section 330, or gradually increase from the width of the resistance increasing section 330 to the width of the first end 341. The detection zone 342 may contain about 20-30 beads 40. The width of the second end 343 of the detecting section 340 affects the arrangement of the beads 40 at the second end 343, and the arrangement of the beads 40 at the second end 343 of the detecting section 340 affects the flowing direction of the liquid. The experimental results according to FIG. 4 show that the cell recovery rate is best when the beads are 200 μm and the width of the second end 343 of the detection section 340 is 250 μm (i.e. only 1 bead 40 can be accommodated), and the cell recovery rate decreases as the width of the second end 343 increases. Therefore, the width of the second end 343 of the detecting section 340 is only required to accommodate 1 bead. The width of the second end 343 of the detection section 340 of the present invention is between 150 and 250 μm. Since the width of the main sensing area 342 is greater than that of the second end 343, the structure of the second end 343 can be reduced from the width of the main sensing area 342 to the width of the second end 343 in a gradual manner (as shown in fig. 3 (a)) or in a step-wise manner (as shown in fig. 3 (B)).

In order to make the bead 40 be retained in the detection main region 342 and not move along with the flow of the liquid, the micro flow channel structure 300 of the present invention includes a bead retaining structure 344. The bead retaining structure 344 is coupled to the second end 343 of the detecting section 340, and the aperture of the bead retaining structure 344 is smaller than the particle size of the bead 40, so that the bead 40 cannot enter the slow flow section 350 through the bead retaining structure 344, and the bead 40 is retained in the detecting main region 342. In addition, the resistance increasing section 330 can prevent the blood sample from flowing back to the expansion section 320 from the detection section 340 due to the insertion of the needle, so that the bead 40 will not move along with the insertion of the needle, and the bead 40 stays in the detection main area 342 stably, thereby facilitating the observation of the condition of the adsorption of the biological substance by the bead 40. The bead-retaining structure 344 of the present invention can be the second end 343 of the detecting section 340, so that the aperture of the second end 343 of the detecting section 340 is smaller than the particle size of the bead 40 (as shown in fig. 3 (B)).

In another embodiment, the bead retaining structure 344 can also be a slow flow section 350 to retain the bead 40 in the detection main zone 342, so that in this case, the depth of the slow flow section 350 is smaller than the particle size of the bead 40 (as shown in fig. 5), so that the bead 40 cannot enter the slow flow section 350. Thus, the bead-retaining structure 344 is coupled to the second end 343 of the detecting section 340, which means that the bead-retaining structure 344 is the second end 343 of the detecting section 340, or is connected to the second end 343 of the detecting section 340.

The utility model discloses an one end of slow flow district section 350 is connected with the second end 343 of listening district section 340, and the other end is connected with blood sample export 360. The aperture of the slow flow section 350 may be circular or polygonal, preferably square. In the embodiment of the present invention, the width of the slow flow section 350 is between 150 and 250 μm, and the depth is between 50 and 100 μm.

The utility model discloses blood sample outlet 360's one end is connected with unhurried current district section 350, and the other end extends to first surface 210 from body 200's second surface 220. Blood cells not captured by the beads 40 will flow through the blood sample outlet 360 to a waste recovery zone (not shown). The blood sample outlet 360 may be a round or square hole, preferably a round hole, and has a diameter of 0.8-1.2 mm.

The following table 1 shows a preferred embodiment of the bead 40 particle size and the pore diameter of each section in the micro flow channel structure 300.

TABLE 1

The material of the substrate 100 of the present invention may be acryl (PMMA), polyethylene terephthalate (PET), Polycarbonate (PC), Polydimethylsiloxane (PDMS), silica gel, rubber, plastic or glass. The material of the body 200 may be acryl (PMMA), polyethylene terephthalate (PET), Polycarbonate (PC), Polydimethylsiloxane (PDMS), silicone, rubber, or plastic. When selecting the materials of the substrate 100 and the body 200, the material characteristics between the substrate 100 and the body 200 must be considered. In the embodiment of the present invention, the substrate 100 is glass, and the body 200 is polydimethylsiloxane.

The present invention also provides another embodiment of a micro flow channel structure 50, as shown in fig. 6. The microchannel structure 50 carries beads 60 and has a structure body 500, the structure body 500 sequentially includes a microfluidic sample inlet 510, a resistance increasing section 520, a detecting section 530, a slow flow section 540 and a microfluidic sample outlet 550 from the inlet to the outlet, wherein the beads 60 are located in the detecting section 530. A bead retaining structure 532 is coupled between the detection section 530 and the buffer section 540 to retain the bead 60 in the detection section 530. When the microfluidic sample enters from the microfluidic sample inlet 510, the microfluidic sample can directly enter the detection section 530 through the resistance increasing section 520, capture the biological substances in the microfluidic sample by the beads 60 in the detection section 530, so as to perform the inspection or treatment of the microfluidic sample, then enter the slow flow section 540, and finally flow out of the microfluidic channel structure 50 from the microfluidic sample outlet 550.

The utility model discloses a preparation method of microchannel chip utilizes the 3D printer to print the master model earlier, and the master model is that photocuring resin washes through 95% alcohol, and UV photocuring 2 minutes back is washed with alcohol once more and is placed the oven and toasts 10 minutes. Food-grade material PDMS liquid is poured into the master mold in proportion, and after 50 minutes and 80 degrees of curing, the master mold is bonded with the glass substrate by an oxygen plasma machine.

Examples of the experiments

Research on grabbing circulating tumor cells by large beads after cultured circulating tumor cell beads are placed in physiological experiment water buffer solution

1. Recovery efficiency and detection limit of large beads (200 μm diameter) in microfluid-free systems

Respectively putting 10, 1000 and 10 ten thousand circulating tumor cells and the beads and 1mL of physiological saline buffer solution (simulated blood environment) into a centrifuge tube, fully and uniformly mixing the circulating tumor cells and the beads in the physiological saline buffer solution, and observing the grasping efficiency of the beads. According to fig. 7, the experimental results show that in the experimental group with only 10 ten thousand circulating tumor cells, 1.5% of the cells (about 1500) are captured by the beads, whereas in the experimental group with 10 and 1000 circulating tumor cells, the beads do not capture any circulating tumor cells, which represents a blood environment of less than 1000 circulating tumor cells, and the beads cannot capture any circulating tumor cells.

2. The recovery efficiency and detection limit of the micro flow channel chip of the present invention are large beads (200 μm in diameter)

Respectively with 10, 50, 100, 500 and 1000 circulating tumor cells and 1mL physiological saline buffer solution mixture, the liquid sample after will mixing flows through the utility model discloses a bead body in the microchannel chip to observe the efficiency of snatching of bead body. According to fig. 8, the experimental result shows and utilizes the utility model discloses a miniflow channel chip contains more than 50 circulating tumor cells in the liquid sample just can snatch, compares in the result that no micro-fluidic system handled (need 10 ten thousand cells could be snatched, as shown in fig. 8), and the limit of listening obviously reduces 2000 times, and utilizes the utility model discloses a miniflow channel chip's recovery efficiency is on average higher than 5%, and is about 3 times higher than no micro-fluidic system's recovery efficiency.

When the number of circulating tumor cells in the blood of a human body is about 50 or more per 10mL on average, the risk of cancer in the human body is high. Therefore, the experiment proves that only the large beads (200 μm in diameter) can not distinguish the risk of cancer, but the large beads can be matched with the micro flow channel chip of the utility model can effectively and accurately capture the circulating tumor cells in the blood, and can more quickly judge whether the cancer is suffered.

Refer to FIGS. 9(A) -9(C), which show the results of separation by the micro flow channel chip of the present invention after the blood specimen of a cancer patient is actually stained. FIG. 9(A) shows the boxes where circulating tumor cells were captured on the clear beads, FIG. 9(B) shows the arrows where leukocytes were erroneously captured by the clear beads, and FIG. 9(C) shows the positions of all captured cells obtained by synthesizing FIGS. 9(A) and 9 (B). This experiment demonstrates that the second stage cancer patient is exposed to the results of the micro flow channel chip of the present invention, which shows that about 13 circulating tumor cells are captured, and only 3 white blood cells are captured (since the number of white blood cells in 1mL blood of a human body is about 10)⁶～10⁷Between individuals, according to the strict definition, at 10⁶One leukocyte cell was estimated, that is, one million leukocytes only capture 3 leukocytes, which is far lower than the error capture rate of the current Cellsearch instrument passing through FDA proof (10)⁶About 3000 to 4000 leukocytes per leukocyte cell) are captured). In addition, the experimental result only needs 30 minutes from the acquisition of the blood sample to the display of the image result, and the time is greatly shortened compared with the conventional method that the pretreatment and the separation of the circulating tumor cells to the reading of the image result take 6 to 9 hours. Therefore, the temperature of the molten metal is controlled,utilize the utility model discloses a micro-channel chip can effectually grab micro-circulating tumor cell in the blood, has very low mistake rate of grabbing, and only needs 30 minutes can obtain the result, so the utility model discloses a micro-channel chip can regard as the preliminary detection to have the quick sieve biochip of cancer.

Other embodiments

1. A micro-channel structure carrying beads with a particle size, comprising a structure body for flowing a micro-fluid sample through the micro-channel structure to be tested or processed, wherein the structure body comprises: a microfluidic sample inlet having a first aperture for entry of the microfluidic sample; a resistance increasing section connected to the microfluidic sample inlet and having a second aperture; a detection section having a first end and a second end, wherein the first end is connected to the resistance increasing section and is used for detecting or processing the microfluidic sample, and the bead is disposed in the detection section; and a bead mooring structure coupled to the second end for mooring the bead in the detection section.

2. The micro flow channel chip as described in embodiment 1, wherein the particle size is 100-200 μm, the diameter is 0.8-1.2mm, the first width is 0.8-1.5mm, the second width is 250 μm, and the first depth is 50-100 μm.

3. The micro flow channel chip as described in embodiment 2, wherein the first depth is 50 μm when the particle size is 100 μm, and the first depth is 100 μm when the particle size is 200 μm.

4. The micro flow channel chip according to embodiment 2, wherein the depth of the expansion section and the resistance-increasing section is 1mm, the width of the detection section is 250 μm to 1.5mm, the depth of the detection section is 20 μm to 50 μm in addition to the particle size, so that the beads are retained in the detection section in a monolayer, and the detection section accommodates 20 to 30 beads.

5. The micro flow channel chip of embodiment 1, wherein the expansion section comprises a first end and a second end, the first end is connected to the blood sample inlet, the second end is connected to the resistance increasing section, and the width of the second end is gradually reduced from the first width to the second width.

6. The micro flow channel chip of embodiment 1, wherein the substrate is made of acryl (PMMA), polyethylene terephthalate (PET), Polycarbonate (PC), Polydimethylsiloxane (PDMS), silicone rubber, plastic, or glass, and the body is made of acryl (PMMA), polyethylene terephthalate (PET), silicone rubber, or plastic.

7. The micro flow channel chip according to embodiment 1, wherein the first surface and the second surface are disposed opposite to each other.

8. A micro-channel structure carrying beads with a particle size, comprising a structure body for flowing a micro-fluid sample through the micro-channel structure to be tested or processed, wherein the structure body comprises: a microfluidic sample inlet having a first aperture for entry of the microfluidic sample; a resistance increasing section connected to the microfluidic sample inlet and having a second aperture; a detection section having a first end and a second end, wherein the first end is connected to the resistance increasing section and is used for detecting or processing the microfluidic sample, and the bead is disposed in the detection section; and a bead mooring structure coupled to the second end for mooring the bead in the detection section.

9. The micro flow channel structure of embodiment 8, wherein the second aperture is smaller than the first aperture to prevent the microfluidic sample from flowing back to the microfluidic sample inlet.

10. The micro flow channel structure of embodiment 8, wherein the structure body further comprises a slow flow section connected to the second end of the detection section, the slow flow section has a third aperture, and the second end of the detection section has a fourth aperture.

11. The micro flow channel structure of embodiment 10, wherein the bead-anchoring structure is the second end of the detection section or the slow flow section.

12. The micro flow channel structure of embodiment 11, wherein when the bead-anchoring structure is the second end of the detection section, the third pore size is smaller than the particle size, and when the bead-anchoring structure is the slow flow section, the fourth pore size is smaller than the particle size, so as to anchor the bead in the detection section.

13. The micro flow channel structure of embodiment 12, wherein the first aperture is a circular hole having a diameter, and wherein: the particle size is 100-200 μm; the diameter is 0.8-1.2 mm; the width of the second aperture is 250 μm, and the depth is 1 mm; the width of the third aperture is 150-250 μm, and the depth is 20-50 μm added to the particle diameter; and the width of the fourth aperture is 150-250 μm and the depth is 50-100 μm.

14. The micro flow channel structure of embodiment 12, wherein the width of the third aperture is the same as the width of the fourth aperture.

15. The micro flow channel structure of embodiment 8, wherein the micro fluid sample is a body fluid or a bacterial fluid.

To sum up, the utility model discloses can really be with novel concept, by making the utility model discloses a collocation of miniflow channel chip and large-scale pearl body can effectually snatch micro-circulating tumor cell in the blood to reduce and grab wrong rate, with the emergence of early judgement cancer. In addition, the micro flow channel chip of the present invention allows the beads to stay in the detecting section statically by the arrangement of the resistance increasing section and the bead mooring structure, so as to facilitate the observation of the condition of the biological material adsorbed by the beads by the user. Moreover, the micro-channel chip only needs 20-30 large beads, which can greatly reduce the manufacturing cost. Therefore, various changes and modifications can be made by one skilled in the art without departing from the true spirit and scope of the disclosure without departing from the scope of the disclosure.

Claims

1. A micro flow channel chip carrying beads having a particle diameter, comprising:

a substrate;

the body is provided with a first surface and a second surface, wherein the second surface is closely covered on the substrate; and

the micro-channel structure is embedded on the second surface, so that the micro-channel structure forms a micro-channel between the body and the substrate, wherein the micro-channel structure comprises:

a blood sample inlet extending from the first surface to the second surface and having a diameter for blood sample entry;

an expansion section connected to the blood sample inlet and having a first width;

a resistance increasing section connected with the expanding section and having a second width;

the detection section is connected with the resistance increasing section, and the bead body is arranged in the detection section; and

a slow flow section connected to the detection section and having a first depth, wherein the particle size is larger than the first depth to prevent the bead from entering the slow flow section, and the second width is smaller than the first width and the diameter to prevent the blood sample from flowing back to the expansion section, thereby retaining the bead in the detection section.

2. The micro flow channel chip as claimed in claim 1, wherein the particle size is 100-200 μm, the diameter is 0.8-1.2mm, the first width is 0.8-1.5mm, the second width is 250 μm, and the first depth is 50-100 μm.

3. The micro flow channel chip as claimed in claim 2, wherein the first depth is 50 μm when the particle size is 100 μm, and the first depth is 100 μm when the particle size is 200 μm.

4. The micro flow channel chip of claim 2, wherein the depth of the expansion section and the resistance-increasing section is 1mm, the width of the detection section is 250 μm to 1.5mm, the depth of the detection section is 20 to 50 μm in addition to the particle size, so that the beads are retained in the detection section in a monolayer form, and the detection section accommodates 20 to 30 beads.

5. The micro flow channel chip of claim 1, wherein the expansion section includes a first end and a second end, the first end is connected to the blood sample inlet, the second end is connected to the resistance increasing section, and the width of the second end is gradually reduced from the first width to the second width.

6. The micro flow channel chip of claim 1, wherein the substrate is made of acryl, polyethylene terephthalate, polycarbonate, polydimethylsiloxane, silicone, rubber, plastic, or glass, and the body is made of acryl, polyethylene terephthalate, polycarbonate, polydimethylsiloxane, silicone, rubber, or plastic.

7. The micro flow channel chip of claim 1, wherein the first surface is disposed opposite to the second surface.

8. A micro-channel structure carrying beads with particle size, comprising a structure body for flowing a micro-fluid sample through the micro-channel structure for testing or processing, wherein the structure body comprises:

a microfluidic sample inlet having a first aperture for entry of the microfluidic sample;

a resistance increasing section connected to the microfluidic sample inlet and having a second aperture;

a detection section having a first end and a second end, wherein the first end is connected to the resistance increasing section and is used for detecting or processing the microfluidic sample, and the bead is disposed in the detection section; and

the bead body mooring structure is coupled to the second end and used for mooring the bead body in the detection section.

9. The micro flow channel structure of claim 8, wherein the second aperture is smaller than the first aperture to prevent backflow of the microfluidic sample back to the microfluidic sample inlet.

10. The micro-fluidic channel structure of claim 8 wherein the structure body further comprises a slow flow section connected to the second end of the detection section, the slow flow section having a third aperture and the second end of the detection section having a fourth aperture.

11. The micro-fluidic channel structure of claim 10, wherein the bead-anchoring structure is the second end of the detection section or the slow flow section.

12. The micro-channel structure of claim 11, wherein the third pore size is smaller than the particle size when the bead-anchoring structure is the second end of the detection section, and the fourth pore size is smaller than the particle size when the bead-anchoring structure is the moderating section, so as to anchor the bead in the detection section.

13. The micro-fluidic channel structure of claim 12 wherein the first aperture is a circular hole having a diameter, and wherein:

the particle size is 100-200 μm;

the diameter is 0.8-1.2 mm;

the width of the second aperture is 250 μm, and the depth is 1 mm;

the width of the third aperture is 150-250 μm, and the depth is 20-50 μm added to the particle diameter; and

the width of the fourth aperture is 150-250 μm, and the depth is 50-100 μm.

14. The micro-channel structure of claim 12 wherein the width of the third aperture is the same as the width of the fourth aperture.

15. The micro-fluidic channel structure of claim 8, wherein the micro-fluidic sample is a body fluid or a bacterial fluid.