CN211246614U - Micro-fluidic chip and formula of punching capillary - Google Patents
Micro-fluidic chip and formula of punching capillary Download PDFInfo
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- CN211246614U CN211246614U CN201921324359.9U CN201921324359U CN211246614U CN 211246614 U CN211246614 U CN 211246614U CN 201921324359 U CN201921324359 U CN 201921324359U CN 211246614 U CN211246614 U CN 211246614U
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Abstract
The utility model provides a micro-fluidic chip and a punching capillary, relating to the technical field of immunodiagnosis equipment, comprising a capillary body, wherein the side wall of the capillary body is provided with a plurality of probe introduction holes, and the inner wall of the capillary body is laid with a plurality of biological probe layers; the utility model has the advantages that the plurality of probe introduction holes are processed on the capillary tube body, the biological probe solution is introduced into the capillary tube body through the probe introduction holes, the biological probes with different types, quantities and concentrations are fixed according to the needs, and the fixing process is simple and convenient; the method can be used for joint detection of various indexes; the carrier used is a capillary tube with low price and extremely low cost.
Description
Technical Field
The utility model relates to an immunodiagnosis equipment technical field particularly, relates to a micro-fluidic chip and formula capillary that punches.
Background
The micro-fluidic chip technology integrates basic operation units of sample preparation, reaction, separation, detection and the like in the processes of biological, chemical and medical analysis on a micron-scale chip, and automatically finishes the whole detection process. In the 90's of the 20 th century, Manz et al proposed the concept of a micro total analysis system, also known as lab-on-a-chip. It has now been developed into a cross-domain encompassing such disciplines as biology, chemistry, medicine, fluidics, electronics, materials and mechanics. However, the micro-processing technology has high process requirements and high cost, so that mass production with low cost is difficult to realize, and the application of the micro-processing technology is greatly limited.
The capillary has the inner diameter generally ranging from millimeter to micron, the substance can be rapidly diffused in the capillary, the utilization rate of a sample can be improved, and the capillary has the advantages of low consumption, low cost, high detection performance and the like, and is widely applied to the fields of chemical analysis, immunodiagnosis and the like. And the capillary has wide sources and simple processing, and is easy to realize large-batch industrial production. However, when the capillary is used as a carrier for immunodiagnosis analysis at present, only one biological probe is fixed on a single capillary, and multi-index combined detection cannot be realized. The capillary and the microfluidic chip are combined, so that the defect that the capillary and the microfluidic chip are independently applied to immunodiagnosis can be effectively overcome, and the development and application of related technologies are promoted.
SUMMERY OF THE UTILITY MODEL
A first object of the utility model is to provide a punching capillary, it uses the capillary as the carrier, processes a plurality of probes on the capillary body and introduces the hole, introduces the hole with biological probe solution through the probe and introduces the capillary body in to on fixing the inner wall of capillary body with biological probe solution, fix multiple biological probe simultaneously on its inner wall, be used for single index to detect or the joint detection of multiple index.
A second object of the present invention is to provide a microfluidic chip, which employs the above-mentioned punched capillary.
A third object of the present invention is to provide a method for preparing a perforated capillary tube, which can prepare the perforated capillary tube rapidly and stably.
The embodiment of the utility model is realized like this:
a punching capillary comprises a capillary body, wherein a plurality of probe introduction holes are formed in the side wall of the capillary body at intervals along the axial direction of the capillary body, a plurality of biological probe layers introduced from the probe introduction holes one by one are laid on the inner wall of the capillary body, and gaps are formed between every two adjacent biological probe layers.
Further, the introduction hole is provided with a sealing layer for sealing the introduction hole.
Furthermore, the biological probe layer is in a closed ring shape and is arranged along the circumferential direction of the inner wall of the capillary tube body.
Furthermore, the capillary tube body is made of glass, quartz, silicon, metal, organic polymer materials or biological polymer materials.
Further, the inner diameter of the capillary tube body is 0.001 mm-10 mm.
Further, the biological probe of the biological probe layer is nucleic acid, polypeptide, protein, antigen, antibody, polysaccharide, ligand or receptor.
Furthermore, the aperture of the probe introducing hole is 50-80% of the inner diameter of the capillary tube body.
Further, the biological probe layer is arranged on one side of the probe introducing hole.
Further, the probe introduction hole faces the biological probe layer.
A micro-fluidic chip comprises a shell and a plurality of the perforated capillaries, wherein the perforated capillaries are packaged in the shell, and the perforated capillaries are mutually connected in series or in parallel.
A preparation method of a perforated capillary tube comprises the following preparation steps:
s1, forming a probe introducing hole in the side wall of a capillary tube body;
s2, introducing a section of biological probe solution into the capillary one by one through the probe introduction holes;
s3, after the introduction is finished, carrying out warm bath on the capillary body for 0.5-1.5 h;
s4, sucking out biological probe solutions at all sections in the capillary one by one through the probe introducing holes;
and S5, adding a buffer solution to clean the inner wall of the capillary tube body.
And further, a step S6 of plugging the probe introducing hole by using a sealing layer.
Further, step S0. is performed to pre-treat the inner wall of the capillary body, so that the inner wall of the capillary body is coupled with an active group capable of being linked with the biological probe.
The utility model has the advantages that:
the utility model can fix biological probes with different types, quantities and concentrations according to the needs, and through processing a plurality of probe introduction holes on the capillary tube body, the biological probe solution is introduced into the capillary tube body through the probe introduction holes, thereby fixing the biological probe solution on the inner wall of the capillary tube body and simultaneously fixing a plurality of biological probes on the inner wall; the method can be used for joint detection of various indexes; the carrier used is a capillary tube with low price and extremely low cost.
Compared with the traditional microfluidic chip, the microfluidic chip manufactured by the capillary tube containing the probe array does not need to process a microchannel and a microstructure by using a micro-processing method, does not need to bond the chip, and greatly reduces the processing cost and difficulty.
Adopt the utility model discloses a method preparation punching capillary, the fixed degree of freedom of biological probe is big, the method is simple, the time investment of preparation is few, the material requirement is low, low cost and easily operation, and can effectually avoid the cross contamination between each biological probe.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention, and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a first schematic view showing the distribution of a biological probe layer and probe-introducing holes provided in example 1 of the present invention;
fig. 2 is a partial cross-sectional view of a perforated capillary tube provided in embodiment 1 of the present invention;
FIG. 3 is a second schematic view showing the distribution of the bioprobe layer and the probe inlet holes provided in example 1 of the present invention;
icon: 1-capillary body, 11-probe introduction hole, 2-biological probe layer, and 3-sealing layer.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. The components of embodiments of the present invention, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the present invention, presented in the accompanying drawings, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative efforts belong to the protection scope of the present invention.
It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, it need not be further defined and explained in subsequent figures.
In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", and the like indicate the position or positional relationship based on the position or positional relationship shown in the drawings, or the position or positional relationship which is usually placed when the product of the present invention is used, and are only for convenience of description and simplification of the description, but do not indicate or imply that the device or element referred to must have a specific position, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.
The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The embodiment of the present invention provides a capillary tube containing a probe array and a method for manufacturing the same.
As shown in FIG. 2, a perforated capillary tube comprises a capillary tube body 1, wherein a plurality of probe introduction holes 11 are formed in the side wall of the capillary tube body 1 at intervals along the axial direction thereof, a plurality of biological probe layers 2 introduced from the probe introduction holes 11 one by one are laid on the inner wall of the capillary tube body 1, a gap is formed between adjacent biological probe layers 2, the introduction holes 11 are provided with a sealing layer 3 for sealing the introduction holes 11, the biological probe layers 2 are in a closed ring shape and are arranged along the circumferential direction of the inner wall of the capillary tube body 1, it should be noted that the plurality of introduction holes 11 are arranged along the extending direction of the capillary tube body 1, but not necessarily in a straight line, the sealing layer 3 may be a sealing tape or the like, the bio-probe layer 2 may be positioned at one side of the probe introduction hole 11, as shown in FIG. 1, the probe introduction hole 11 may be formed to face the bioprobe layer 2 as shown in FIG. 3.
The inner diameter of the capillary body 1 is 0.001mm to 10mm, the length of the capillary body 1 is not limited, the length of the capillary body 1 is selected according to actual needs, the length of the capillary body 1 is usually 0.01mm to 10000mm, the capillary body 1 is made of glass, quartz, silicon, metal, organic polymer material (such as plastic) or biopolymer material, the diameter of the probe introducing hole 11 is 50% to 80% of the inner diameter of the capillary body 1. in the present embodiment, the diameter of the probe introducing hole is selected according to actual use, the distance between the probe introducing holes 11 is determined according to the actual length of the bioprobe layer 2, the capillary body 1 is a straight capillary, and in other embodiments, the capillary body 1 may be a bent capillary according to actual needs.
The biological probes of the biological probe layer 2 are nucleic acids, polypeptides, proteins, antigens, antibodies, polysaccharides, ligands or receptors, as required by the application scenario.
A preparation method of a perforated capillary tube comprises the following preparation steps:
s1, forming a probe introducing hole 11 in the side wall of a capillary tube body 1;
s2, introducing a section of biological probe solution into the capillary one by one through the probe introduction holes 11;
s3, after the introduction is finished, the capillary body 1 is subjected to warm bath for 0.5-1.5 h;
s4, sucking out biological probe solutions at all sections in the capillary one by one through the probe introduction holes 11;
s5, adding a buffer solution to clean the inner wall of the capillary tube body 1;
s6, the probe introduction hole 11 is blocked by the blocking layer 3.
The temperature of the capillary body 1 is 4-45 deg.C, and is determined according to the specific method and the specific type of biological probe, for example, the temperature is 25-45 deg.C when the magnetic beads are coated with chemiluminescence, and the temperature of the Elisa plate is 4-37 deg.C; the buffer solution may be phosphate buffer, carbonate buffer, Tris, Hepes or Mes.
In some embodiments, step S0. is further included before step S1 to pretreat the inner wall of the capillary body 1, so that the inner wall of the capillary body 1 is coupled with a reactive group capable of being linked with the biological probe, where the reactive group is a hydroxyl group, a thiol group, a carboxyl group, an aldehyde group, an amino group, or the like; because some biological probes have or are modified to couple with active groups such as hydroxyl, sulfydryl, carboxyl, aldehyde group, amino and the like, when a biological probe solution contacts with the inner wall of the capillary body 1, the biological probe solution and the active groups on the inner wall of the capillary body 1 can generate chemical action and be linked together, so that the biological probe is fixed on the inner wall of the capillary body 1.
Example 1
The capillary body 1 used in the embodiment is a glass capillary, and the inner diameter of the capillary body 1 is 1mm, and the length is 10 cm;
cleaning the capillary tube body, including acid washing and alkali washing, to obtain a clean capillary tube body;
three probe introduction holes 11 are drilled in the capillary body, the diameter of the probe introduction holes 11 being between 0.5 and 0.8mm, the holes being spaced 2cm apart.
Preparing primary antibodies corresponding to three tumor markers (CEA, NSE and CA125) and preparing a solution for later use;
adding an anti-solution of tumor markers into the capillary body from each probe introduction hole 11, one probe introduction hole 11 corresponding to one antibody, placing in a 37 ℃ warm bath for 1h, washing with a buffer solution, and drying.
In this embodiment, all the biological probe solution is introduced into the capillary body 1 at one time and then fixed, but in some other embodiments, the biological probe solution may be introduced once and fixed.
Example 2
This example includes all the contents of example 1, except that the inner wall of the capillary body 1 is pretreated before introducing the bio-probe and the sealant, and the specific operations are as follows: the inner wall of the capillary body 1 is pretreated to couple active groups which can be linked with the biological probe on the inner wall of the capillary body 1, and the pretreatment steps are as follows:
soaking the capillary tube body in 10% NaOH solution, reacting at 100 ℃ for 10min, washing with deionized water, and drying;
soaking the dried capillary tube body in the piranha solution, reacting at 80 ℃ for 1h, washing with deionized water, and drying;
soaking the dried capillary tube body in a mixed solution with a volume ratio of 95:3:2 (ethanol: water: APTES), reacting at room temperature in a dark place for 2 hours, respectively cleaning with ethanol and deionized water, drying, and placing in a 120 ℃ oven for 1 hour;
and soaking the capillary tube body dried in the previous step in glutaraldehyde mixed solution for reaction at room temperature in a dark place for one night, cleaning with acetone and deionized water, and drying.
Of course, the above-mentioned method is not intended to limit the present invention, and any method known to those skilled in the art can be used to couple the reactive group to the inner wall of the capillary body 1, and the specific method is selected according to the reactive group required in the actual use.
Example 3
The embodiment provides a microfluidic chip, which comprises a shell and a plurality of perforated capillaries manufactured as in embodiment 1 or embodiment 2, wherein the perforated capillaries are packaged in the shell, and the perforated capillaries are connected in series or in parallel.
Example 4
Taking 100 mu l of standard solution or human serum containing the three tumor markers mentioned in the embodiment 1 and the embodiment 2;
introducing a standard solution or serum into a microchannel (namely a perforated capillary) of the microfluidic chip mentioned in example 3, incubating for 1h at 37 ℃, taking out, washing and drying;
a fluorescence-labeled secondary antibody mixed solution was prepared, introduced into and filled in the microchannel, incubated at 37 ℃ for 1 hour, taken out, washed and dried.
Fluorescence detection was performed using a Typhoon & Storm series multifunctional laser scanning imaging system.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A perforated capillary tube, comprising: the biological probe comprises a capillary tube body (1), wherein a plurality of probe introduction holes (11) are formed in the side wall of the capillary tube body (1) at intervals along the axial direction of the capillary tube body, a plurality of biological probe layers (2) introduced from the probe introduction holes (11) one by one are laid on the inner wall of the capillary tube body (1), and gaps are formed between every two adjacent biological probe layers (2).
2. The perforated capillary of claim 1, wherein: the introduction hole (11) is provided with a sealing layer (3) for sealing the introduction hole (11).
3. The perforated capillary of claim 1, wherein: the biological probe layer (2) is in a closed ring shape and is arranged along the circumferential direction of the inner wall of the capillary tube body (1).
4. The perforated capillary of claim 1, wherein: the capillary tube body (1) is made of glass, quartz, silicon, metal, organic polymer materials or biological polymer materials.
5. The perforated capillary of claim 1, wherein: the inner diameter of the capillary tube body (1) is 0.001 mm-10 mm.
6. The perforated capillary of claim 1, wherein: the biological probes of the biological probe layer (2) are nucleic acids, polypeptides, proteins, antigens, antibodies, polysaccharides, ligands or receptors.
7. The perforated capillary of claim 1, wherein: the aperture of the probe introducing hole (11) is 50-80% of the inner diameter of the capillary tube body (1).
8. The perforated capillary of claim 1, wherein: the biological probe layer (2) is arranged on one side of the probe introducing hole (11).
9. The perforated capillary of claim 1, wherein: the probe introduction hole (11) is opposite to the biological probe layer (2).
10. A microfluidic chip, characterized in that: the punching capillary tube comprises a shell and a plurality of punching capillary tubes according to any one of claims 1 to 9, wherein the punching capillary tubes are packaged in the shell, and the punching capillary tubes are mutually connected in series or in parallel.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201921324359.9U CN211246614U (en) | 2019-08-15 | 2019-08-15 | Micro-fluidic chip and formula of punching capillary |
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| CN201921324359.9U CN211246614U (en) | 2019-08-15 | 2019-08-15 | Micro-fluidic chip and formula of punching capillary |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110614127A (en) * | 2019-08-15 | 2019-12-27 | 成都工业学院 | Punching capillary tube and application and preparation method thereof |
| CN112570052A (en) * | 2020-12-07 | 2021-03-30 | 厦门大学 | Micro-fluidic device containing probe array and micro-fluidic chip with side channels |
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2019
- 2019-08-15 CN CN201921324359.9U patent/CN211246614U/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110614127A (en) * | 2019-08-15 | 2019-12-27 | 成都工业学院 | Punching capillary tube and application and preparation method thereof |
| CN112570052A (en) * | 2020-12-07 | 2021-03-30 | 厦门大学 | Micro-fluidic device containing probe array and micro-fluidic chip with side channels |
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