阅读说明：本技术 变量光栅微信号分离装置及其制造方法 (Variable grating micro-signal separation device and manufacturing method thereof ) 是由 吕才树 于 2020-04-23 设计创作，主要内容包括：本发明公开了一种变量光栅微信号分离装置及其制造方法,所述分离装置包括毛细管、激发光源和信号接收器,所述毛细管位于所述激发光源与信号接收器之间,所述毛细管的外表面设有光栅套,所述光栅套为吸光材料；所述光栅套有两个,分别为第一光栅套和第二光栅套,所述第一光栅套和第二光栅套之间有间隙,所述间隙的宽度大于或等于毛细管中单个待检测物质颗粒的尺寸,且小于两个待检测物质颗粒的尺寸；所述第一光栅套和第二光栅套远离所述间隙的一端均在所述毛细管上延伸至所述光接收镜头所覆区域之外；所述分离装置的制造方法是借助间隙生成器在第一光栅套和第二光栅套之间形成间隙。本发明可有效减少待测样本中信号的叠加,提高了检测的准确性。(The invention discloses a variable grating micro-signal separation device and a manufacturing method thereof, wherein the separation device comprises a capillary tube, an excitation light source and a signal receiver, the capillary tube is positioned between the excitation light source and the signal receiver, the outer surface of the capillary tube is provided with a grating sleeve, and the grating sleeve is made of light absorption materials; the two grating sleeves are respectively a first grating sleeve and a second grating sleeve, a gap is arranged between the first grating sleeve and the second grating sleeve, and the width of the gap is larger than or equal to the size of a single substance particle to be detected in the capillary tube and smaller than the sizes of the two substance particles to be detected; one ends of the first grating sleeve and the second grating sleeve, which are far away from the gap, extend out of the region covered by the light receiving lens on the capillary; the separating device is manufactured by forming a gap between the first grating housing and the second grating housing by means of a gap generator. The invention can effectively reduce the superposition of signals in the sample to be detected and improve the detection accuracy.)

1. A variable grating micro-signal separation device comprises a capillary tube, an excitation light source and a signal receiver, wherein the capillary tube is positioned between the excitation light source and the signal receiver, and a light receiving lens of the signal receiver corresponds to an emitting head of the excitation light source; the two grating sleeves are respectively a first grating sleeve and a second grating sleeve, a gap is arranged between the first grating sleeve and the second grating sleeve, and the width of the gap is larger than or equal to the size of a single substance particle to be detected in the capillary tube and smaller than the sum of the sizes of the two substance particles to be detected; one end of the first grating sleeve, which is far away from the second grating sleeve, extends out of the area covered by the light receiving lens on the capillary tube, and one end of the second grating sleeve, which is far away from the first grating sleeve, extends out of the area attached to the light receiving lens on the capillary tube.

2. The variable grating micro signal splitting device according to claim 1, wherein the sum of the lengths of the first and second grating sleeves is greater than the diameter of the light receiving lens.

3. The variable grating micro signal separation device of claim 1, wherein the first grating and the second grating are hollow sleeve structures and are fixed on the outer surface of the capillary tube by gluing.

4. The variable grating micro signal splitting device of claim 1, wherein the first grating and the second grating are coated directly on the outer surface of the capillary.

5. The variable grating micro signal splitting device of claim 1, wherein the light absorbing material is a black light absorbing material.

6. The variable grating micro-signal separation device according to any one of claims 1 to 5, wherein the gap between the first grating sleeve and the second grating sleeve is aligned with the midpoint of the light receiving lens.

7. The variable grating micro signal splitting device of claim 6, wherein the first grating sleeve and the second grating sleeve each have a length greater than 1/2 times the diameter of the light receiving lens.

8. The variable grating micro signal separation device according to any one of claims 1 to 5, further comprising a capillary holder, wherein the capillary holder is located at both ends of the capillary tube, and the capillary tube is fixed on the capillary holder.

9. A method for manufacturing a variable grating micro signal separation device according to any one of claims 1 to 8, wherein a gap generator is selected, the gap generator is installed on the capillary tube, and the plane of the gap generator is ensured to be vertical to the capillary tube; then, respectively covering the first grating sleeve and the second grating sleeve on the surfaces of the capillary tubes on two sides of the gap generator; finally, the gap generator is removed.

10. The method of manufacturing of claim 9, wherein the gap generator is a film.

Technical Field

The invention relates to the field of bioengineering sample detection, in particular to a variable grating micro-signal separation device and a manufacturing method thereof.

Background

When a biological sample is detected, the signal receiver simultaneously receives signals generated by a plurality of sample particles or gene fragments flowing through the capillary at one time, and the signal intensities are superposed, so that the accurate judgment of the signals is influenced. At present, the problem has been solved by a chip method, in which a small flow channel for placing sample particles or gene fragments one by one is formed on a chip in order to achieve the purpose of individually detecting the sample particles and the gene fragments, but the method has a large process difficulty and is inconvenient to implement. Therefore, there is a need to develop other devices and methods that achieve separation of individual sample particle signals.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a variable grating micro-signal separation device and a manufacturing method thereof.

In order to achieve the purpose, the technical scheme adopted by the invention is that the variable grating micro-signal separation device comprises a capillary tube, an excitation light source and a signal receiver, wherein the capillary tube is positioned between the excitation light source and the signal receiver, a light receiving lens of the signal receiver corresponds to an emitting head of the excitation light source, a grating sleeve is arranged on the outer surface of the capillary tube, the grating sleeve covers the capillary tube, and the grating sleeve is made of light absorption materials; the two grating sleeves are respectively a first grating sleeve and a second grating sleeve, a gap is arranged between the first grating sleeve and the second grating sleeve, and the width of the gap is larger than or equal to the size of a single substance particle to be detected in the capillary tube and smaller than the sum of the sizes of the two substance particles to be detected; one end of the first grating sleeve, which is far away from the second grating sleeve, extends out of the area covered by the light receiving lens on the capillary tube, and one end of the second grating sleeve, which is far away from the first grating sleeve, extends out of the area attached to the light receiving lens on the capillary tube.

In an embodiment of the invention, a sum of lengths of the first grating sleeve and the second grating sleeve is greater than a diameter of the light receiving lens.

In an embodiment of the invention, the first grating and the second grating are hollow sleeve structures and are fixed on the outer surface of the capillary tube by gluing.

In an embodiment of the invention, the first grating and the second grating are coatings and are directly coated on the outer surface of the capillary.

In an embodiment of the invention, the light absorbing material is a black light absorbing material.

In an embodiment of the invention, a gap between the first grating sleeve and the second grating sleeve is directly opposite to a midpoint of the light receiving lens.

In an embodiment of the invention, the lengths of the first grating sleeve and the second grating sleeve are both greater than 1/2 of the diameter of the light receiving lens.

In an embodiment of the present invention, the separation device further includes a capillary support, the capillary support is located at two ends of the capillary, and the capillary is fixed on the capillary support.

Firstly, selecting a gap generator, mounting the gap generator on the capillary tube, and ensuring that the plane where the gap generator is positioned is vertical to the capillary tube; then, respectively covering the first grating sleeve and the second grating sleeve on the surfaces of the capillary tubes on two sides of the gap generator; finally, the gap generator is removed.

In an embodiment of the invention, the gap generator is a thin film.

The technical scheme has the following beneficial effects:

the two grating sleeves are arranged on the capillary tube at the position of the light receiving lens of the signal receiver, and the size of the gap between the first grating sleeve and the second grating sleeve is selected according to needs, so that the sample particles or gene segments flowing through the capillary tube are detected independently, a plurality of micro signals generated simultaneously when a plurality of sample particles or gene segments flow through the light receiving lens to cover the visual field at one time are avoided, the superposition of the signals generated simultaneously is avoided, and the accuracy of sample detection is improved. The micro-signal separation device is convenient to manufacture, controllable in process and suitable for detecting sample particles or gene fragments with various sizes by adjusting the gap between the first grating sleeve and the second grating sleeve.

Drawings

FIG. 1 is a schematic diagram of a sample detection structure according to an embodiment of the present invention;

FIG. 2 is an enlarged view at A in FIG. 1;

FIG. 3 is a schematic cross-sectional view of the structure of FIG. 1;

fig. 4 is an enlarged view at B in fig. 3.

Description of reference numerals: the device comprises a capillary tube 100, an excitation light source 1, a signal receiver 2, a gap 101, a substance to be detected 111, an emission head 10, a light receiving lens 20, a grating sleeve 3, a first grating sleeve 31 and a second grating sleeve 32.

Detailed Description

The invention will now be further described with reference to the following examples and figures 1 to 4.

A variable grating micro-signal separation device is shown in figure 1 and comprises a capillary tube 100, an excitation light source 1 and a signal receiver 2, wherein the capillary tube 100 is located between the excitation light source 1 and the signal receiver 2, the excitation light source 1 is arranged on one side of the capillary tube 100, an emission head 10 of the excitation light source 1 is used for emitting excitation light, the emitted excitation light penetrates through the transparent capillary tube 100 and hits a substance to be detected 111 flowing through the capillary tube 100, the substance to be detected 111 is a sample particle or a gene fragment and is composed of a plurality of particles or gene fragments, and a fluorescence signal emitted by the fluorescence signal penetrates through the transparent capillary tube 100 again and enters the signal receiver 2 located on the other side of the capillary tube 100. The signal receiver 2 has a light receiving lens 20 extending to the surface of the capillary 100, and the fluorescent signal is received to the signal receiver 2 through the light receiving lens 20. The light receiving lens 20 and the transmitting head 10 are located on the same axis to ensure comprehensive and accurate signal reception.

In this embodiment, the outer surface of the capillary tube 100 is provided with a grating sleeve 3, as shown in fig. 1-2, the grating sleeve covers the capillary tube 100, the grating sleeve 3 is a black light-absorbing sleeve, and is fixed on the outer surface of the capillary tube 100 by gluing; in other embodiments, the grating housing 3 may also be a light absorbing coating applied directly to the surface of the capillary tube 100. The two grating sleeves 3 are respectively a first grating sleeve 31 and a second grating sleeve 32, and a gap 101 is formed between the first grating sleeve 31 and the second grating sleeve 32, as shown in fig. 2. The axial direction of the capillary 100 is defined as the width direction of the gap 101. In order to enable individual detection of all particles of each substance to be detected 111, the width of said gap 101 is greater than or equal to the size of a single substance particle to be detected in the capillary 100 and less than the sum of the sizes of two substance particles to be detected. In practical application, the width of the gap allows a certain tolerance, that is, the width of the gap is theoretically larger than the size of the substance particles to be detected in a certain proportion and smaller than the sum of the sizes of the two substance particles to be detected in a certain range, so that the detection effect and the process manufacturing can be considered at the same time. Meanwhile, one end of the first grating sleeve 31, which is far away from the second grating sleeve 32, extends out of the area covered by the light receiving lens 20 on the capillary 100, and one end of the second grating sleeve 32, which is far away from the first grating sleeve 31, extends out of the area attached to the light receiving lens 20 on the capillary 100, so that only the substance to be detected 111 located in the gap 101 between the first grating sleeve 31 and the second grating sleeve 32 can obtain excitation light and generate a micro signal, while the substance to be detected 111 located in the grating sleeve does not reach the top, so that no micro signal is generated.

Further, the sum of the lengths of the first and second grating housings 31 and 32 is larger than the diameter of the light receiving lens 20. Therefore, when the first grating sleeve 31 and the second grating sleeve 32 are sleeved on the capillary 100, all light-sensitive areas of the light-receiving lens 20 except the light-receiving lens 20 corresponding to the gap 101 left on the capillary 100 can be shielded, as shown in fig. 2, so that the unwanted micro-signals are prevented from entering the light-receiving lens 20.

Further, the gap between the first grating housing 31 and the second grating housing 32 is aligned with the midpoint of the light receiving lens 20, that is, the gap 101 left on the capillary 100 for transmitting fluorescence generated by sample particles or gene fragments is located at the midpoint of the light receiving lens 20 of the signal receiver 2, thereby ensuring the accuracy of signal acquisition. At this time, the lengths of the first grating sleeve 31 and the second grating sleeve 32 on both sides of the gap are both greater than 1/2 of the diameter of the light receiving lens 20, that is, by extending the ends of the first grating sleeve 31 and the second grating sleeve 32 away from the midpoint of the light receiving lens 20 on the capillary tube to the outside of the area covered by the light receiving lens 20, the light receiving lens 20 is effectively covered, so as to prevent the fluorescent signal generated by the other substance to be detected 111 flowing under the area covered by the light receiving lens 20 from entering the light receiving lens 20, that is, effectively shield other signals, and only allow the single fluorescent signal generated by the same particle or gene segment located at the gap to enter the light receiving lens 20.

Meanwhile, the cylindrical surfaces of the first grating sleeve 31 and the second grating sleeve 32 can effectively reflect stray light, as shown in fig. 4, so that the interference of stray signals is reduced, the signal-to-noise ratio is improved, a stable signal source can be obtained, the accuracy, the repeatability and the sensitivity can be correspondingly improved, and the processing of the signals becomes simple and easy. Therefore, the structure of the grating sleeve 3 with a specific structure greatly optimizes the detection process of the substance to be detected, and obtains a more real detection result.

Further, the capillary holder (not shown) is located at both ends of the capillary 100 for fixing the capillary 100, maintaining the "straightness" of the capillary 100.

Compared with the sequencing chip with the complex process, the variable grating sleeve 3 is arranged on the surface of the capillary tube 100, so that the method has the advantages of ensuring the detection accuracy, greatly simplifying the process, reducing the manufacturing cost, being more extensive and flexible in applicability, and being capable of conveniently meeting the detection requirements of particles or gene fragments to be detected with various sizes.

A manufacturing method of a variable grating micro-signal separation device comprises the following steps: firstly, selecting a gap generator, and sleeving the gap generator on the capillary tube 100 on a microscopic scale to ensure that the plane where the gap generator is located is perpendicular to the capillary tube 100; then, the first grating sleeve 31 and the second grating sleeve 32 are respectively sleeved on the capillary 100 at two sides of the gap generator, so that the first grating sleeve 31 and the second grating sleeve 32 are both tightly attached to the gap generator; and finally, removing the gap generator to obtain the adjustable grating separation device. In this embodiment, the selected gap generator is a film, and films with different thicknesses can be selected according to the size of the sample particles or gene fragments to be detected.

The above-described embodiments are intended to illustrate rather than to limit the invention, and any changes and alterations made without inventive step within the spirit and scope of the claims are intended to fall within the scope of the invention.