Sample concentration method and detection method

Abstract

The invention relates to a sample concentration method and a detection method.The sample concentration method comprises the steps that the temperature of a sample in a sample containing groove is adjusted, so that when the actual liquid level of the sample drops to the target liquid level, the actual liquid level is controlled to be kept at the target liquid level; wherein the target liquid level is the liquid level, corresponding to the target volume of the sample, in the sample containing groove, and the target volume is determined according to the initial volume of the sample and the preset concentration multiple. According to the sample concentration method, the liquid level of the sample is accurately controlled to be concentrated to the target liquid level and kept at the target liquid level, and the concentration precision is improved.

Description

Technical Field

[0001] The present application relates to the field of concentration technology, and in particular to a sample concentration method and a detection method. Background Art

[0002] Sample concentration is used to increase the concentration of solutes, for example, by removing part of the solvent in the sample. Solvent evaporation is a common concentration method, which can be achieved using concentrators such as fully automatic water bath nitrogen blowing concentrators and rotary evaporators. However, in the prior art, these concentrators are only suitable for concentrating large doses of samples, and the concentration accuracy of these concentrators is not high, especially for small doses of samples.

[0003] In view of the problem that the above-mentioned concentrator is only suitable for large-dose samples, there are chip-type concentrators in the prior art to concentrate small-dose samples, see CN1696639A and CN107189929A. However, these chip-type concentrators have complex structures and can only concentrate specific samples.

[0004] In order to solve the problem of low concentration accuracy of the above-mentioned concentrator, there are means in the prior art to improve the concentration accuracy by detecting the sample liquid level. For example, a liquid level gauge is provided on the concentrating device. During the concentration process, the liquid level gauge detects the sample liquid level in real time and transmits the detected information to the control system. The control system determines whether the sample liquid level is at the target liquid level based on the information. When the sample liquid level is at the target liquid level, the control system controls the heating element to stop heating. However, on the one hand, this makes the control process of the concentrating device complicated. On the other hand, when the heating element stops heating, the temperature of the sample is still high, and the sample will continue to evaporate, causing the sample liquid level to be lower than the target liquid level, which seriously affects the concentration accuracy, especially for small-dose samples. Summary of the invention

[0005] The present application provides a sample concentration method and a detection method to solve the problem of low concentration accuracy.

[0006] In a first aspect, the sample concentration method of the present application comprises:

[0007] adjusting the temperature of the sample in the sample holding tank so that when the actual liquid level of the sample drops to the target liquid level, the temperature of the sample at the actual liquid level is equal to the dew point temperature at the location of the sample holding tank, or

[0008] The vapor partial pressure at the location of the sample holding tank is equal to the saturated vapor pressure, or

[0009] The relative humidity at the location of the sample holding slot is equal to the saturated humidity,

[0010] so that the actual liquid level remains at the target liquid level,

[0011] The target liquid level is the liquid level in the sample holding tank corresponding to the target volume of the sample, and the target volume is determined according to the initial volume of the sample and the preset concentration multiple. When the sample is concentrated using the sample concentration method of the present application, when the actual liquid level of the sample drops to the target liquid level, the actual liquid level of the sample is controlled to remain at the target liquid level, that is, when the actual liquid level of the sample drops to the target liquid level, evaporation and condensation are kept in balance, so that the liquid level of the sample is maintained at the target liquid level, thereby improving the accuracy of sample concentration.

[0012] In a second aspect, the detection method of the present application includes the sample concentration method described in the first aspect, and further includes:

[0013] After the sample is concentrated, the light detection component detects the emitted light or absorbed light of the sample in the sample holding tank.

[0014] After the sample is concentrated using the sample concentration method of the present application, the detection method can detect the concentration of the sample to ensure that the concentration of the sample is the target concentration. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to make the content of this application easier to understand, the following further describes the implementation of this application in detail with reference to the accompanying drawings.

[0016] Figure 1 A schematic diagram of the working principle of the present application is shown.

[0017] Figure 2 A schematic diagram showing a sample holding component according to a first embodiment of the present application is shown.

[0018] Figure 3 A schematic diagram showing a sample holding component according to a second embodiment of the present application is shown.

[0019] Figure 4 A schematic diagram showing a sample holding component according to a third embodiment of the present application is shown.

[0020] Figure 5 A schematic diagram showing a sample holding component according to a fourth embodiment of the present application is shown.

[0021] Figure 6 A schematic diagram showing a sample holding component according to a fifth embodiment of the present application is shown.

[0022] Figure 7 A schematic diagram of a sample concentration device according to a first embodiment of the present application is shown.

[0023] Figure 8A schematic diagram of a sample concentration device according to a first embodiment of the present application is shown.

[0024] Fig. 9 A schematic diagram of a sample concentrating device according to a fifth embodiment of the present application is shown.

[0025] Fig.10 A temperature simulation diagram of the sample concentration device according to the first embodiment of the present application is shown.

[0026] Fig.11 A temperature simulation diagram of a sample concentrating device according to a fifth embodiment of the present application is shown.

[0027] Fig.12 A schematic diagram of a sample concentrating device according to an embodiment of the present application is shown, wherein the covering component is a lid.

[0028] Fig.13 A schematic diagram of a sample concentration device according to an embodiment of the present application is shown, wherein the covering component is a chamber body.

[0029] Fig.14 A schematic diagram of a sample concentration device according to an embodiment of the present application is shown, wherein the covering component is a lid, and a humidity control module is disposed on the lid.

[0030] Fig.15 A schematic diagram of a sample concentrating device according to an embodiment of the present application is shown, wherein the sample concentrating device includes a light detection component.

[0031] Fig.16 A schematic diagram of a sample concentrating device according to an embodiment of the present application is shown, wherein the sample concentrating device includes a light detection component.

[0032] Fig.17 A flow chart of the sample concentration method of the present application is shown.

[0033] Fig.18 A schematic diagram showing a method for manufacturing a sample concentration device according to an embodiment of the present application is shown.

[0034] Fig.19 A schematic diagram showing a method for manufacturing a sample concentration device according to yet another embodiment of the present application is shown.

[0035] Reference numerals:

[0036] 100. Sample holding component;

[0037] 110, sample holding tank; 111, opening; 113, side surface; 115, bottom surface;

[0038] 130, side wall; 131, sample concentration area; 1311, first position; 1313, second position; 133, first variable temperature area; 135, middle area; 137, second variable temperature area;

[0039] 150. Bottom wall;

[0040] 200. Temperature control module;

[0041] 210. Heating components;

[0042] 230. Refrigeration components;

[0043] 300, covering parts;

[0044] 310, lid;

[0045] 330, warehouse body;

[0046] 400. Humidity control module;

[0047] 410. Humidification unit;

[0048] 430, drying unit;

[0049] 500, light detection component;

[0050] 510. Light source;

[0051] 520, detector;

[0052] 540. Light-blocking layer. DETAILED DESCRIPTION

[0053] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and through specific implementation methods. It is understood that the specific implementation methods described herein are only used to explain the present invention, rather than to limit the present invention. It is also necessary to explain that, for ease of description, only the parts related to the present invention are shown in the accompanying drawings, rather than all of them.

[0054] Some directional words are defined in the present application. Unless otherwise stated, the directional words used, such as "up", "down", "left", "right", "inside" and "outside", are used for ease of understanding and therefore do not constitute a limitation on the scope of protection of the present application.

[0055] In the present application, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0056] In the description of this application, unless otherwise clearly specified and limited, the terms "connected", "connected", and "fixed" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0057] definition

[0058] Dew point temperature: The temperature at which the air is cooled to saturation while the water vapor content in the air remains unchanged and the air pressure remains constant, that is, the temperature at which the water vapor in the air turns into dew drops. When the air is saturated with water vapor, the air temperature is the same as the dew point temperature; when the water vapor is not saturated, the air temperature is higher than the dew point temperature; when the air is supersaturated with water vapor, the air temperature is lower than the dew point temperature. The difference between the air temperature and the dew point temperature can indicate the degree to which the water vapor in the air is away from saturation. The dew point temperature can be calculated using conventional calculation formulas in the prior art, which will not be described in detail here. The dew point temperature can be measured using a dew point meter.

[0059] How it works

[0060] According to the definition of dew point temperature, when the temperature of the sample is higher than the dew point temperature, the evaporation rate of the sample is greater than the condensation rate, so the liquid level of the sample will gradually decrease; when the temperature of the sample is equal to the dew point temperature, the evaporation rate and condensation rate of the sample reach equilibrium, so the liquid level of the sample remains basically unchanged.

[0061] like Figure 1As shown, when the sample needs to be concentrated from the initial liquid level to the target liquid level below the initial liquid level, the temperature of the sample above the target liquid level can be made higher than the dew point temperature, the temperature at the target liquid level is equal to the dew point temperature, and the temperature below the target liquid level is lower than the dew point temperature, so that the sample can drop from the initial liquid level to the target liquid level, and when the sample drops to the target liquid level, since the temperature of the upper surface of the sample is equal to the dew point temperature, the evaporation rate and condensation rate of the sample reach a balance, and the actual liquid level of the sample is maintained at the target liquid level.

[0062] Specifically, the target volume of the sample after concentration can be calculated based on the initial volume of the sample before concentration and the multiple of concentration required. The liquid level corresponding to the target volume in the sample holding tank can be calculated based on the target volume and the geometric dimensions of the sample holding tank, and the liquid level is the target liquid level. By adjusting the temperature of the side wall of the sample holding tank so that the temperature above the target liquid level is greater than the dew point temperature, the temperature of the target liquid level is equal to the dew point temperature, and the temperature below the target liquid level is lower than the dew point temperature, the actual liquid level of the sample can be maintained at the target liquid level.

[0063] Sample Concentrator

[0064] The sample concentrating device of the present application is suitable for concentrating small doses of samples, but does not exclude the concentrating of medium or large doses of samples.

[0065] As an example, the sample can be a biological sample dissolved in a solvent (such as water). In addition, the sample can also be a biological sample in liquid form, such as saliva, blood, tissue fluid, bacterial culture fluid, protein or nucleic acid extract, etc.

[0066] It should be noted that the term "small dose" refers to a sample volume between 1 microliter and 3200 microliters, such as a sample volume of 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, 150, 200, 300, 400, 500, 1000, 1200, 1500, 2000, 2500, 3000, 3200 microliters. The term "medium and large doses" refers to a sample volume greater than 3200 microliters, such as a sample volume of 4000, 5000, 6000, 7000, 8000, 9000, 10000, 100000 microliters, etc.

[0067] Since the total volume of a small-dose sample is small, evaporation has a greater impact on the volume. When the conventional heating method in the prior art is used to concentrate it, it is not easy to control the sample volume, so the concentration accuracy is not easy to control. In addition, even for medium and large-dose samples, there is still a problem that the concentration accuracy is not easy to control.

[0068] The sample concentration device of the present application forms a temperature gradient including a dew point temperature inside the sample, thereby precisely controlling the concentration process of the sample to improve the concentration accuracy.

[0069] like Figure 2 As shown, the sample concentrating device includes a sample holding component 100. In the present application, the sample holding component 100 is placed flat on a horizontal support surface such as a desktop as an example to illustrate the detailed structure of the sample holding component 100. It can be understood that when the placement direction of the sample holding component 100 changes, such as when it is tilted or inverted, the positional relationship between the various structures described below will change accordingly.

[0070] like Figure 2 As shown, the sample holding component 100 includes a sample holding tank 110, and the sample holding tank 110 is used to hold the sample to be concentrated. Specifically, the top of the sample holding tank 110 has an opening 111, and the side surface 113 and the bottom surface 115 of the sample holding tank 110 are both closed. The sample can be added to the sample holding tank 110 through the opening 111, and is limited by the side surface 113 and the bottom surface 115, so as to be held in the sample holding tank 110.

[0071] As an example, a pipette (not shown) may be used to add a sample to the sample receiving well 110 , and a pipette may be used to remove a sample from the sample receiving well 110 .

[0072] like Figure 2 As shown, in the longitudinal section of the sample holding tank 110, the side surface 113 may include one or more straight lines, one or more curved lines, or a combination of one or more straight lines and one or more curved lines; similarly, the bottom surface 115 may include one or more straight lines, one or more curved lines, or a combination of straight lines and curved lines. Curves include arc curves, conic curves, spline curves, polynomial curves, etc.

[0073] Specifically, the side surface 113 may include a straight line segment, and the straight line segment may be vertically arranged or inclinedly arranged.

[0074] As an example, the shape of the sample receiving groove 110 can be a prism, a pyramid, or other geometric shapes. Specifically, the sample receiving groove 110 can be a triangular prism, a quadrangular prism, an inverted cone, an inverted truncated cone, or the like.

[0075] exist Figure 2In the embodiment, the sample receiving groove 110 is in the shape of an inverted truncated cone, and the groove width of the sample receiving groove 110 decreases uniformly from top to bottom along the depth direction of the sample receiving groove 110, so as to facilitate the calculation of the volume of the sample receiving groove 110, and further facilitate the calculation of the height of the upper surface of the sample when a sample of known volume is contained in the sample receiving groove 110. In addition, the inverted truncated cylindrical sample receiving groove 110 makes the surface area of ​​the upper surface of the sample larger than other positions, which is conducive to the evaporation of the sample from the upper surface into the air.

[0076] It can be understood that the number of the sample holding slots 110 can be one or more.

[0077] When there are multiple sample receiving slots 110, the multiple sample receiving slots 110 can be arranged regularly or irregularly. When the multiple sample receiving slots 110 are arranged regularly, the multiple sample receiving slots 110 can be arranged in a linear array or a circular array.

[0078] In addition, when the number of the sample receiving grooves 110 is plural, the plurality of sample receiving grooves 110 may have the same or different shapes.

[0079] In a specific embodiment, Figure 3 As shown, the sample holding component 100 may include three sample holding slots 110 arranged side by side, and the three sample holding slots 110 have the same shape.

[0080] like Figure 2 As shown, the sample holding component 100 (or the sample holding groove 110 ) includes a bottom wall 150 constituting the bottom surface 115 and a side wall 130 constituting the side surface 113 .

[0081] like Figure 2 As shown, the side wall 130 includes a sample concentration area 131. When the sample is contained in the sample containing groove 110, the sample concentration area 131 is concentrated along the depth direction (i.e., Figure 2 In the up and down directions), the samples may contact the sample concentration area 131, and then the samples will gradually evaporate, causing the actual liquid level of the samples to gradually decrease.

[0082] In one possible implementation, Figure 2 As shown, the entire side wall 130 is made of a heat-conducting material, so the temperature of the entire side wall 130 can be adjusted to facilitate sample evaporation. Figure 2 In the example, the entire side wall 130 can be regarded as the sample concentration area 131. Figure 2 In the sample holding component 100 , the initial liquid level and the target liquid level of the sample are both located in the sample concentrating area 131 .

[0083] In another possible implementation, Figure 4 As shown, the upper portion of the side wall 130 is made of a heat insulating material, and the lower portion of the side wall 130 is made of a heat conductive material, so that the temperature of the lower portion of the side wall 130 can be adjusted to facilitate the evaporation of the sample. Figure 4 In the embodiment, the lower part of the side wall 130 can be regarded as the sample concentration area 131. Figure 4 In the sample holding component 100 , the initial liquid level and the target liquid level of the sample are usually located at the lower part of the side wall 130 , that is, in the sample concentration area 131 .

[0084] In another possible implementation, Figure 5 As shown, the upper portion of the side wall 130 is made of a heat-conducting material, and the lower portion of the side wall 130 is made of a heat-insulating material, so that the temperature of the upper portion of the side wall 130 can be adjusted to facilitate the evaporation of the sample. Figure 5 In the example, the upper portion of the side wall 130 can be regarded as the sample concentration area 131. Figure 5 In the sample holding component 100 , the initial liquid level and the target liquid level of the sample are usually located at the upper part of the side wall 130 , that is, in the sample concentration area 131 .

[0085] In another possible implementation, Figure 6 As shown, the upper and lower parts of the side wall 130 are made of heat-conducting materials, and the middle part of the side wall 130 is made of heat-insulating materials. Therefore, the temperature of the upper and lower parts of the side wall 130 can be adjusted, but the temperature of the middle part of the side wall 130 is difficult to accurately adjust. At this time, the entire side wall 130 can be regarded as the sample concentration area 131. However, it should be noted that the initial liquid level of the sample is usually located at the upper part of the side wall 130, and the target liquid level of the sample is usually located at the middle part of the side wall 130. For example, during concentration, the temperature of the upper part of the side wall 130 can be made greater than the dew point temperature, and the temperature of the lower part of the side wall 130 can be made less than the dew point temperature. Then, the upper surface of the sample located at the upper part of the side wall 130 will gradually move downward until it moves to a certain position in the middle part of the side wall 130, at which the temperature of the upper surface of the sample is equal to the dew point temperature.

[0086] It should be noted that the term "thermal conductive material" refers to a material with a thermal conductivity greater than 50 W / (m K), such as thermal conductive materials such as silicon, ceramics, various metals, silicon carbide, aluminum nitride, etc. In contrast to thermal conductive materials, thermal insulating materials can be porous silicon, silicon nitride, polyimide, etc.

[0087] It should be noted that the bottom wall 150 can be made of a heat-conducting material or a heat-insulating material. In addition, the bottom wall 150 and the side wall 130 can be made of the same material or different materials.

[0088] When there are multiple sample receiving slots 110 , the side walls 130 of different sample receiving slots 110 may use the same or different thermally conductive materials; similarly, the bottom walls 150 of different sample receiving slots 110 may use the same or different thermally conductive materials.

[0089] In addition, when there are multiple sample receiving slots 110, the side walls 130 of different sample receiving slots 110 may have the same or different structures. Figure 2 The side walls 130 of other sample receiving grooves 110 are formed as follows: Figure 5 The structure shown.

[0090] like Figure 7 As shown, in order to adjust the temperature of the sample concentration area 131, the sample concentration device further includes a temperature control module 200, which is configured to control the temperature of the sample concentration area 131 so that a temperature interval is formed in the sample concentration area 131, and the temperature in the temperature interval continuously decreases from top to bottom along the depth direction of the sample holding slot 110, and the temperature interval includes the dew point temperature of the position where the sample holding slot 110 is located. In this way, the temperature near the top of the temperature interval is greater than the dew point temperature, and the temperature of the samples corresponding to these positions is also greater than the dew point temperature, so the samples at these positions can evaporate into the air until the liquid level of the sample drops to the target liquid level, and the temperature of the sample at the target liquid level is equal to the dew point temperature, and the evaporation and condensation of the sample are kept balanced, so the liquid level of the sample is kept at the target liquid level.

[0091] The term "the location of the sample receiving tank 110" may be the space inside the sample receiving tank 110. In addition, when the environment above the sample receiving tank 110 is relatively stable (e.g., the air pressure and air flow rate are substantially constant), the term "the location of the sample receiving tank 110" may also be the space that is connected to the inside of the sample receiving tank 110 and is located above the sample receiving tank 110. In addition, when the surrounding (e.g., the side, the bottom, etc.) of the sample receiving tank 110 is relatively stable, the term "the location of the sample receiving tank 110" may also be the space that is connected to the inside and the top of the sample receiving tank 110 and is located around the sample receiving tank 110.

[0092] As an example, the term “where the sample receiving groove 110 is located” may be an evaporation chamber to be described later.

[0093] It should be noted that the dew point temperature may be lower than the ambient temperature of the location where the sample holding tank 110 is located, so that the overall temperature of the sample is relatively low, thereby avoiding excessive evaporation of the sample and reducing the concentration accuracy.

[0094] In one example, the ambient temperature at the location of the sample holding slot 110 may be 26° C., and the relative humidity may be 70%, at which time the dew point temperature is approximately 20° C.

[0095] In another example, the ambient temperature at the location of the sample holding slot 110 may be 24° C., and the relative humidity may be 75%, at which time the dew point temperature is approximately 19° C.

[0096] like Figure 7 As shown, the temperature control module 200 includes a heating component 210 and a cooling component 230. The heating component 210 is used to heat the first position 1311 of the sample concentration area 131 so that the temperature of the first position 1311 is greater than the dew point temperature. The cooling component 230 is used to heat the second position 1313 of the sample concentration area 131 that is lower than the first position 1311 along the depth direction of the sample holding groove 110 so that the temperature of the second position 1313 is less than the dew point temperature. In this way, a temperature interval with continuously changing temperature is formed in the sample concentration area 131, and the temperature in the temperature interval continuously decreases from the first position 1311 to the second position 1313. Therefore, there must be a position between the first position 1311 and the second position 1313 where the temperature is equal to the dew point temperature. The position where the temperature is equal to the dew point temperature is the target liquid level. When the structure and material of the side wall 130 are determined, the thermal conductivity of each position of the side wall 130 is known, and the side wall 130 can be simulated or calculated to determine the temperature distribution of the side wall 130 when the temperature of the first position 1311 and the second position 1313 changes, thereby determining the target liquid level.

[0097] In a possible implementation, the heating end of the heating component 210 can heat the first position 1311 by heat conduction. For example, the heating end of the heating component 210 is directly connected to the first position 1311 (see Figure 7 ), thereby heating the first position 1311. For another example, the heating end of the heating component 210 can be indirectly connected to the first position 1311 (see Figure 8 ), for example, a heat-conducting component made of a heat-conducting material is arranged between the heating end of the heating component 210 and the first position 1311, so as to heat the first position 1311.

[0098] In another possible implementation, the heating end of the heating component 210 can also heat the first position 1311 by heat radiation. For example, the heating end of the heating component 210 is close to but not in contact with the first position 1311, and the heating component 210 radiates heat outward, thereby heating the first position 1311.

[0099] As an example, the heating component 210 may be a heating electrode or a semiconductor cooling sheet.

[0100] In a possible implementation, the cooling end of the cooling component 230 can cool the second position 1313 by heat conduction. For example, the cooling end of the cooling component 230 is directly connected to the second position 1313 (see Figure 7 ), thereby cooling the second position 1313. For another example, the cooling end of the cooling component 230 is indirectly connected to the second position 1313 (see Figure 8 ), for example, a heat-conducting component made of a heat-conducting material is arranged between the cooling end of the cooling component 230 and the second position 1313, so as to cool the second position 1313.

[0101] In another possible implementation, the cooling end of the cooling component 230 can also cool the second position 1313 by heat radiation. For example, the cooling end of the cooling component 230 is close to but not in contact with the second position 1313, and the cooling component 230 absorbs heat from the outside, thereby cooling the second position 1313.

[0102] As an example, the refrigeration component 230 may be liquid nitrogen.

[0103] It should be noted that the term "first position 1311" refers to a certain position (or region) of the sample concentrating region 131, but not the entire sample concentrating region 131. In other words, not the entire sample concentrating region 131 is directly or indirectly heated by the heating component 210, but only the first position 1311 is directly or indirectly heated, and other positions in the sample concentrating region 131 are indirectly heated by heat conduction with the first position 1311. The temperature of the first position 1311 may be T_hot.

[0104] It is understandable that due to the heat loss in the process of heat conduction, the temperature of other positions in the sample concentration area 131 except the first position 1311 will be lower than that of the first position 1311, and generally, the farther away from the first position 1311, the lower the temperature. In addition, when the material of the sample concentration area 131 is a uniform material, it can be considered that in the depth direction of the sample holding tank 110, the temperature in the temperature range gradually and evenly decreases from top to bottom.

[0105] It should be noted that the term "second position 1313" refers to a certain position (or region) of the sample concentrating region 131, but not the entire sample concentrating region 131. In other words, not the entire sample concentrating region 131 is directly or indirectly cooled by the cooling component 230, but only the second position 1313 is directly or indirectly cooled, and other positions in the sample concentrating region 131 are indirectly cooled by heat conduction with the second position 1313. The temperature of the second position 1313 may be T_cold.

[0106] It is understandable that due to the heat loss in the process of heat conduction, the temperature of other positions in the sample concentration area 131 except the second position 1313 will be higher than the second position 1313, and generally, the farther away from the second position 1313, the higher the temperature. In addition, when the material of the sample concentration area 131 is a uniform material, it can be considered that in the depth direction of the sample holding groove 110, the temperature in the temperature range gradually and evenly decreases from top to bottom.

[0107] exist Figure 2 In the example, since the entire side wall 130 can be regarded as the sample concentration area 131, it is only necessary to ensure that the first position 1311 is higher than the second position 1313. For example, the first position 1311 is the top of the side wall 130, and the second position 1313 is the bottom of the side wall 130. For another example, the first position 1311 is the middle of the side wall 130, and the second position 1313 is the bottom of the side wall 130. For another example, the first position 1311 is the top of the side wall 130, and the second position 1313 is the middle of the side wall 130.

[0108] exist Figure 4 In the embodiment, since the lower part of the side wall 130 can be regarded as the sample concentration area 131, it is only necessary to ensure that the first position 1311 and the second position 1313 are both located in the sample concentration area 131 and the first position 1311 is higher than the second position 1313. For example, the first position 1311 is located at the upper end of the lower part of the side wall 130, and the second position 1313 is located at the lower end of the lower part of the side wall 130.

[0109] exist Figure 5 In the embodiment, since the upper portion of the side wall 130 can be regarded as the sample concentration region 131, it is only necessary to ensure that the first position 1311 and the second position 1313 are both located in the sample concentration region 131 and the first position 1311 is higher than the second position 1313. For example, the first position 1311 is located at the upper end of the upper portion of the side wall 130, and the second position 1313 is located at the lower end of the upper portion of the side wall 130.

[0110] exist Figure 6 In the embodiment, since the middle portion of the side wall 130 is made of heat-insulating material, the first position 1311 is set at the upper portion of the side wall 130, and the second position 1313 is set at the lower portion of the side wall 130. In this way, the temperature at a certain position in the middle portion of the side wall 130 can be equal to the dew point temperature.

[0111] like Figure 7As shown, the side wall 130 includes a first variable temperature region 133 made of a heat-conducting material, and the sample concentration region 131 is located in the first variable temperature region 133. When the heating component 210 heats the first position 1311 of the sample concentration region 131, and the cooling component 230 cools the second position 1313 of the sample concentration region 131, a temperature range with a temperature decreasing from top to bottom is formed in the first variable temperature region 133. When the heating component 210 makes the temperature of the first position 1311 higher than the dew point temperature, and the cooling component 230 makes the temperature of the second position 1313 lower than the dew point temperature, the temperature range may include the dew point temperature. Figure 4 and Figure 5 For the situation, please refer to Figure 7 Applicably, the side wall 130 may also include a first variable temperature region 133 .

[0112] like Fig. 9 As shown, the side wall 130 includes a first variable temperature region 133, an intermediate region 135, and a second variable temperature region 137 which are stacked in sequence from top to bottom along the depth direction of the sample holding groove 110. The thermal conductivity of the intermediate region 135 is lower than the thermal conductivity of the first variable temperature region 133 and the thermal conductivity of the second variable temperature region 137. In particular, the thermal conductivity of the intermediate region 135 is at least one order of magnitude lower than the thermal conductivity of the first variable temperature region 133 and the thermal conductivity of the second variable temperature region 137, thereby being able to form a significant temperature change between the upper surface and the lower surface of the intermediate region 135.

[0113] In a specific embodiment, the material of the first variable temperature region 133 may be silicon, the material of the middle region 135 may be silicon oxide, and the material of the second variable temperature region 137 may be silicon. Since the thermal conductivity of silicon oxide is two orders of magnitude lower than that of silicon, the temperature changes sharply above and below the middle region 135, the temperature of the upper surface of the middle region 135 is slightly higher than the dew point temperature, the temperature of the lower surface of the middle region 135 is slightly lower than the dew point temperature, and the temperature at a certain position of the middle region 135 is equal to the dew point temperature.

[0114] In addition, the material of the first variable temperature region 133 may also be ceramics, various metals, silicon carbide, aluminum nitride, etc. Similarly, the material of the second variable temperature region 137 may also be ceramics, various metals, silicon carbide, aluminum nitride, etc. The material of the first variable temperature region 133 may be the same as or different from the material of the second variable temperature region 137.

[0115] In addition, the material of the middle region 135 may also be porous silicon, silicon nitride, polyimide, etc.

[0116] exist Fig. 9In the embodiment, the thickness of the first variable temperature region 133 may be 50 micrometers to 2000 micrometers. The thickness of the middle region 135 may be 500 nanometers to 3000 nanometers, and the thickness of the second variable temperature region may be 5 micrometers to 200 micrometers. Therefore, compared with the first variable temperature region 133 and the second variable temperature region 137, the middle region 135 has a very small thickness, so that the temperature at the location of the middle region 135 can be considered as the dew point temperature.

[0117] When the heating component 210 makes the temperature of the first variable temperature region 133 greater than the dew point temperature, and the cooling component 230 makes the temperature of the second variable temperature region 137 less than the dew point temperature, the temperature at a certain position in the middle region 135 may be equal to the dew point temperature.

[0118] In order to adjust the position corresponding to the dew point temperature in the sample concentration area 131 up and down so as to concentrate the sample to different multiples, the heating component 210 and the cooling component 230 may be of at least the following two types.

[0119] In the first type, the amount of heat released by the heating component 210 per unit time can be adjusted. Thus, the temperature of the first position 1311 can be adjusted by controlling the heating component 210, thereby adjusting the upper limit of the temperature range. For example, when the upper limit of the temperature range needs to be increased, the heating component 210 can release more heat per unit time. For example, when the upper limit of the temperature range needs to be decreased, the heating component 210 can release less heat per unit time.

[0120] Similarly, the amount of heat released by the refrigeration component 230 within a unit time can also be adjusted. Thus, by controlling the refrigeration component 230, the temperature of the second position 1313 can be adjusted, thereby adjusting the lower limit of the temperature range. For example, when the lower limit of the temperature range needs to be increased, the refrigeration component 230 can absorb less heat per unit time. For example, when the lower limit of the temperature range needs to be lowered, the refrigeration component 230 can absorb more heat per unit time.

[0121] By adjusting the heating component 210 and / or the cooling component 230 , the temperature range in the sample concentration area 131 can be changed, thereby adjusting the position in the sample concentration area 131 corresponding to the dew point temperature.

[0122] In the second type, the amount of heat released by the heating component 210 per unit time cannot be adjusted. In this case, a heating component 210 that can generate appropriate heat per unit time can be selected to adjust the upper limit of the temperature range. For example, when the upper limit of the temperature range needs to be increased, a heating component 210 that releases more heat per unit time can be selected. For example, when the upper limit of the temperature range needs to be lowered, a heating component 210 that releases less heat per unit time can be selected.

[0123] Similarly, the amount of heat released by the refrigeration component 230 per unit time cannot be adjusted. In this case, a refrigeration component 230 that can absorb appropriate amount of heat per unit time can be selected to adjust the lower limit of the temperature range. For example, when the lower limit of the temperature range needs to be increased, a refrigeration component 230 that absorbs less heat per unit time can be selected. For example, when the lower limit of the temperature range needs to be lowered, a refrigeration component 230 that absorbs more heat per unit time can be selected.

[0124] By replacing the heating component 210 and / or the cooling component 230 , the temperature range in the sample concentration area 131 can be changed, thereby adjusting the position in the sample concentration area 131 corresponding to the dew point temperature.

[0125] It should be noted that the heating component 210 of the first type can be used in combination with the cooling component 230 of the second type. The cooling component 230 of the first type can be used in combination with the heating component 210 of the second type.

[0126] In summary, by adjusting the upper and lower limits of the temperature range, the temperature range can include the dew point temperature of the sample holding tank 110. The position in the sample concentration area 131 where the temperature corresponds to the dew point temperature is the target liquid level (or target position), that is, the final liquid level after the sample evaporates. When the liquid level of the sample is at the target liquid level, the liquid level of the sample remains at the target liquid level, completing the concentration process.

[0127] In one implementation, the shape of the sample holding tank is a prism or a pyramid. In this case, the formula for calculating the target liquid level is as follows:

[0128] h=H*(Td-T_cold) / (T_hot-T_cold), where:

[0129] h is the target liquid level;

[0130] H is the total height of the sample holding tank;

[0131] Td is the dew point temperature, where T is the temperature at the location of the sample holding slot, and RH is the relative humidity at the location of the sample holding slot;

[0132] T_cold is the temperature of the cooling component or the temperature at the lower end of the sample holding tank, and T_cold is less than Td;

[0133] T_hot is the temperature of the heating component or the temperature of the upper end of the sample holding tank, and T_hot is greater than Td.

[0134] like Fig.10 As shown, for Figure 7In a specific embodiment of the sample concentrator shown, the total height H of the sample holding tank 110 is 700 microns, the temperature T_hot of the first position 1311 is 85° C., the temperature T_cold of the second position 1313 is 15° C., the ambient temperature of the sample holding tank 110 is 26° C., the relative humidity is 70%, and the dew point temperature is about 20° C. Under this working condition, the target liquid level h can be calculated to be 50 microns according to the formula described above.

[0135] like Fig.11 As shown, for Fig. 9 In a specific embodiment of the sample concentrator shown, the total height H of the sample holding tank 110 is 700 microns, the temperature T_hot of the first position 1311 is 80° C., the temperature T_cold of the second position 1313 is 10° C., the ambient temperature of the sample holding tank 110 is 24° C., the relative humidity is 75%, and the dew point temperature is about 19° C. Under this working condition, the target liquid level h can be calculated to be 90 microns according to the formula described above.

[0136] Optionally, in order to detect whether the liquid level of the concentrated sample is at the target liquid level, the sample concentration device may further include a liquid level sensor (not shown), which is used to detect the liquid level of the sample in the sample holding tank 110. Those skilled in the art will appreciate that the liquid level sensor is not necessary in the sample concentration device of the present application, because in the setting of the present application, the temperature is not controlled by the liquid level measured by the liquid level sensor. On the contrary, the present application ensures that the sample liquid level is at the target liquid level by forming a temperature gradient in the sample. However, in some embodiments, the liquid level sensor may be enabled to measure the liquid level of the sample after concentration is completed, so as to verify whether the liquid level of the concentrated sample is at the target liquid level. In some other embodiments, the liquid level sensor may be enabled continuously or at fixed time intervals throughout the concentration process. It is conceivable that by comparing the measured data of the temperature setting and / or the liquid level drop speed with the empirical data or theoretical data, an early warning can be provided when necessary (for example, in the case of a significant deviation from the empirical data), thereby providing an effective monitoring of the concentration process.

[0137] It should be noted that the liquid level sensor can be an optical, capacitive or acoustic sensor.

[0138] Optionally, in order to facilitate the determination of the dew point temperature at the location of the sample holding slot 110 and make the dew point temperature relatively stable, the sample concentration device may also include a covering component 300, and the covering component 300 is used to form a closed evaporation chamber above the sample holding slot 110 to prevent the evaporation chamber from being connected to the complex external environment, thereby ensuring that the dew point temperature in the evaporation chamber is relatively stable.

[0139] like Fig.12 As shown, in a possible embodiment, the covering component 300 includes a cover 310, and the cover 310 is suitable for covering the top of the sample holding component 100, so as to cover the top of the sample holding slot 110, thereby forming a closed evaporation chamber above the sample holding slot 110. The cover 310 and the top of the sample holding slot 110 can be detachably arranged to add a sample to the sample holding slot 110 and remove the sample from the sample holding slot 110.

[0140] like Fig.13 As shown, in another possible embodiment, the covering component 300 includes a chamber body 330, the chamber body 330 includes a sealable accommodation space, and the sample accommodation component 100 can be located in the accommodation space, so that the chamber body 330 covers the top of the sample accommodation slot 110, thereby forming a sealed evaporation chamber above the sample accommodation slot 110. The chamber body 330 can include a box body and a box cover, and the box cover can be detachably mounted on the box cover. When the box cover is closed, the accommodation space is sealed; when the box cover is opened, the accommodation space is open. The sample accommodation component 100 can be fixed on the box body, or can be detachably mounted on the box body.

[0141] like Fig.14 As shown, based on the covering component 300, the sample concentration device may further include a humidity control module 400, which is connected to the evaporation chamber. The humidity control module 400 is used to control the humidity in the evaporation chamber, thereby controlling the dew point temperature.

[0142] As an example, the humidity control module 400 can be disposed on the cover member 300, for example, the humidity control module 400 is mounted on the lid 310 or the bin body 330. However, the humidity control module 400 can also be installed independently, for example, only the output end or the input end of the humidity control module 400 is connected to the evaporation chamber.

[0143] like Fig.14 As shown, the humidity control module 400 may include a humidifying unit 410 and / or a drying unit 430. The humidifying unit 410 is used to increase the humidity in the evaporation chamber, and the drying unit 430 is used to reduce the humidity in the evaporation chamber. The dew point temperature in the evaporation chamber can be adjusted by the humidifying unit 410 and / or the drying unit 430.

[0144] For example, before concentration begins, the dew point temperature in the evaporation chamber is adjusted to the target dew point temperature by the humidifying unit 410 and / or the drying unit 430. For another example, during the concentration process and after concentration is completed, the dew point temperature in the evaporation chamber is kept constant by the humidifying unit 410 and / or the drying unit 430.

[0145] As an example, the humidifying unit 410 may introduce water vapor into the evaporation chamber.

[0146] As an example, the drying unit 430 may introduce dry gas, such as inert gas such as nitrogen, helium, neon, etc., into the evaporation chamber. By introducing dry gas into the evaporation chamber, water vapor in the evaporation chamber may be discharged to the outside.

[0147] like Fig.15 As shown, optionally, the sample concentration device may further include a light detection component 500 , which is configured to detect emitted light (such as fluorescence or phosphorescence) or absorbed light (such as ultraviolet light or visible light) of the sample located in the sample holding tank 110 .

[0148] like Fig.15 As shown, in one possible embodiment, the light detection assembly includes a light source 510, a detector 520 and a data analysis system (not shown). The light source 510 is configured to emit light that is irradiated into the sample. The light source can be a point light source, preferably a quantum light source. The detector 520 is configured to receive a light signal emitted from the sample or absorbed by the sample and to generate a detection signal in response to the received light signal. The detector 520 and the data analysis system can be connected in a wired or wireless manner, and the data analysis system is configured to receive the detection signal and generate a detection result in response to the received detection signal.

[0149] like Fig.15 As shown, the light source 510 can be disposed in the bottom wall 150 , and the light emitting end of the light source 510 faces the sample receiving groove 110 , so that the light emitted by the light source 510 can directly illuminate the sample located inside the sample receiving groove 110 .

[0150] like Fig.15 As shown, the detector 520 may be disposed below the bottom wall 150. In order to allow the light emitted by the sample to irradiate the detector 520, the position of the bottom wall 150 corresponding to the bottom of the sample receiving groove 110 is transparent.

[0151] In one possible implementation, Fig.15 As shown, in the up and down directions, the light source 510 can be located between the bottom of the groove and the detector 520, and there is no interference between the light source 510 and the detector 520 (that is, the light source 510 and the detector 520 are staggered), so that the light emitted by the light source 510 can illuminate the sample, and the light signal emitted by the sample can illuminate the detector 520.

[0152] In one possible implementation, Fig.16As shown, the light detection assembly further includes a light blocking layer 540, which is disposed on the side of the light source 510 away from the sample receiving slot 110, so that the light emitted by the light source 510 will not propagate toward the side away from the sample receiving slot 110. The light blocking layer can be stacked on the transparent bottom wall 150. In addition, another light blocking layer 150 can be stacked below the transparent bottom wall 150. The detector 520 is disposed on the lower light blocking layer 540, so that the detector 520 can only detect the light signal emitted by the sample in one of the sample receiving slots 110. The cooling component 230 can be connected below the lower light blocking layer 540.

[0153] exist Fig.16 In the illustrated embodiment, the material of the light blocking layer 540 is opaque and is a thermally conductive material.

[0154] The following is a possible application scenario of the sample concentration device provided in this application:

[0155] At present, detection methods such as immune cell method, flow cytometry, PCR quantitative detection or immunomagnetic bead enrichment combined with chemical light or fluorescence method are already common, but the number of cells that can be detected by the immune cell method is small and the efficiency is low; the sensitivity of flow cytometry detection is low; the PCR detection method is time-consuming and complicated to operate, and for samples with low contamination levels, it is difficult for existing detection methods to accurately detect them, so bacterial enrichment treatment is required before detection; in addition, some cells to be tested are unculturable and cannot be detected using traditional plate detection methods. The sample concentration device of the present application provides a cell quantitative detection device with a high degree of integration, which can simultaneously detect low-concentration and high-concentration samples, and is fast and efficient.

[0156] In this scenario, the following steps are included:

[0157] 1. Perform fluorescent staining on the sample to be tested so that the target sample can excite fluorescence;

[0158] 2. Inject a quantitative amount of the sample to be tested into the sample concentration device to concentrate the sample to be tested;

[0159] 3. After the concentration is completed, turn on the light source 510 to excite the target sample to emit fluorescence;

[0160] 4. The detector 520 receives the light signal of the fluorescence;

[0161] 5. Upload the optical signal to a data analysis system for counting and display.

[0162] After low-concentration samples are concentrated, the detection efficiency can be greatly improved.

[0163] Sample concentration method

[0164] The sample concentration method of the present application is implemented using the sample concentration device described above, such as Fig.17 As shown, sample enrichment methods include:

[0165] S10: Adjusting the temperature of the sample in the sample holding tank 110 so that when the actual liquid level of the sample drops to the target liquid level, the actual liquid level is controlled to remain at the target liquid level; wherein the target liquid level is the liquid level in the sample holding tank 110 corresponding to the target volume of the sample, and the target volume is determined based on the initial volume of the sample and a preset concentration multiple.

[0166] As a first implementation method of controlling the actual liquid level to remain at the target liquid level, controlling the actual liquid level to remain at the target liquid level includes: making the temperature of the sample at the actual liquid level equal to the dew point temperature at the location of the sample holding tank 110 .

[0167] As a second implementation manner of controlling the actual liquid level to remain at the target liquid level, controlling the actual liquid level to remain at the target liquid level includes: making the vapor partial pressure at the location of the sample holding slot 110 equal to the saturated vapor pressure.

[0168] As a third implementation manner of controlling the actual liquid level to remain at the target liquid level, controlling the actual liquid level to remain at the target liquid level includes: making the relative humidity at the location of the sample holding slot 110 equal to the saturated humidity.

[0169] Specifically, S10 may also include:

[0170] S11: Make the temperature of the sample between the initial liquid level and the target liquid level greater than the dew point temperature, the temperature of the sample at the target liquid level equal to the dew point temperature, and the temperature of the sample below the target liquid level less than the dew point temperature; wherein the initial liquid level is the liquid level in the sample holding tank 110 corresponding to the initial volume of the sample.

[0171] Specifically, S11 may also include:

[0172] S12: The temperature of the sample concentration region 131 of the side wall 130 is adjusted by the temperature control module 200 disposed on the side wall 130 of the sample holding tank 110; wherein the initial liquid level and the target liquid level are both located in the sample concentration region.

[0173] Further, when the side wall 130 includes the first variable temperature area 133, S12 may further include:

[0174] S12a: The first position 1311 of the sample concentration area 130 is heated by the heating component 210 of the temperature control module 200 so that the temperature of the first position 1311 is greater than the dew point temperature; and the second position 1313 in the sample concentration area 131 which is lower than the first position 1311 is cooled by the cooling component 230 of the temperature control module 200 so that the temperature of the second position 1313 is lower than the dew point temperature.

[0175] Alternatively, when the side wall 130 includes the first variable temperature area 133, the middle area 135, and the second variable temperature area 137, S12 may further include:

[0176] S12b: The heating component 210 heats the upper end of the first temperature variable region 133, and the cooling component 230 cools the lower end of the first temperature variable region 133, so that the temperature at the target liquid level is equal to the dew point temperature.

[0177] Furthermore, when the sample concentration device further includes a liquid level sensor, the sample concentration method further includes:

[0178] S31: Detecting the actual liquid level of the sample;

[0179] S32: Determine whether the actual liquid level is at the target liquid level.

[0180] Furthermore, when the sample concentration device further includes a covering component 300, the sample concentration method further includes:

[0181] S40: During the concentration of the sample, the covering member 300 forms a closed evaporation chamber above the sample receiving tank.

[0182] Furthermore, when the sample concentration device further includes a covering component 300 and a humidity control device, the sample concentration method may further include:

[0183] S50: During the concentration of the sample, the humidity control module 400 controls the humidity in the evaporation chamber to keep the dew point temperature constant.

[0184] Detection Methods

[0185] The detection method includes the aforementioned sample concentration method, and the detection method also includes:

[0186] S60: After the sample concentration is completed, the optical detection component 500 performs optical detection on the sample in the sample holding tank.

[0187] Specifically, in a possible implementation, S60 may include:

[0188] S61: the light source 510 emits light that irradiates the sample, generating a light signal in the sample;

[0189] S62: The detector 520 receives the light signal emitted from the sample or absorbed by the sample, and generates a detection signal in response to the light signal;

[0190] S63: The data analysis system receives the detection signal and generates a detection result in response to the detection signal.

[0191] Manufacturing method

[0192] As described above, the sample concentrator of the present application is particularly suitable for concentrating small doses of samples. In order to be suitable for concentrating small doses of samples, the sample holding tank has a smaller size, such as micrometer level. To this end, the sample holding component 100 can be manufactured using MEMS technology.

[0193] like Fig.18 As shown, when the sample holding component 100 only includes the first variable temperature area 133 and does not include the middle area 135 and the second variable temperature area 137, the manufacturing method of the sample concentrating device includes:

[0194] a. obtaining a silicon wafer having a thickness of 200 μm to 1500 μm, wherein the upper and lower surfaces of the silicon wafer are polished;

[0195] b. Through the low pressure chemical vapor deposition (LPCVD) process, a silicon oxide layer of tetraethyl orthosilicate (TEOS) / borosilicate glass (BPSG) / phosphosilicate glass (PSG) is grown on the upper and lower surfaces of the silicon wafer, respectively. The thickness of the silicon oxide layer is 300 microns to 1000 microns, with high optical transmittance and controllable stress;

[0196] c. Ti&Pt / Ti&Mo is deposited on the silicon oxide layer on the upper surface of the silicon wafer by magnetron sputtering / evaporation coating process to form a heating electrode (i.e., heating component 210), wherein the thickness of the deposited Ti is 10 nanometers to 40 nanometers, and the thickness of the deposited Pt or Mo is 150 nanometers to 350 nanometers;

[0197] d. Depositing a silicon oxide layer on the upper surface of the heating electrode and the upper surface of the upper silicon oxide layer by plasma enhanced chemical vapor deposition (PECVD) or sub-atmospheric pressure chemical vapor deposition (SACVD) to improve the passivation performance. In this step, the thickness of the silicon oxide layer is 2 microns to 4 microns.

[0198] e. Etching pads on the heating electrodes to form wet etching or deep silicon mask windows; and

[0199] f. Use a wet solution, such as potassium hydroxide (KOH) or tetramethylammonium hydroxide (TMAH) for wet etching; or use dry etching to make a sample concentration device.

[0200] It should be noted that, between step b and step c, the manufacturing method may further include:

[0201] A layer of LPCVD silicon nitride with a thickness of 100 to 300 nanometers can be added to the surface of the silicon oxide layer on the upper surface of the silicon wafer as a mask for wet etching.

[0202] like Fig.19 As shown, when the sample holding component 100 includes both the first variable temperature region 133, the middle region 135 and the second variable temperature region 137, the manufacturing method of the sample concentrating device includes:

[0203] a. obtaining a silicon wafer having a thickness of 200 μm to 1500 μm, wherein the upper and lower surfaces of the silicon wafer are polished;

[0204] b. Depositing a silicon oxide layer of tetraethyl orthosilicate (TEOS), borosilicate glass (BPSG), or phosphosilicate glass (PSG) by a low pressure chemical vapor deposition (LPCVD) process, with a thickness of 500 nm to 2500 nm, high optical transmittance, and controllable stress (as a thermal insulation material, i.e., the middle region 135);

[0205] c. Bonding two silicon wafers;

[0206] d. Thinning and polishing, surface roughness Ra is better than 2 nanometers;

[0207] e. Depositing a silicon oxide layer of tetraethyl orthosilicate (TEOS), borosilicate glass (BPSG), or phosphosilicate glass (PSG) by a low pressure chemical vapor deposition (LPCVD) process to a thickness of 500 nm to 2000 nm;

[0208] A layer of LPCVD silicon nitride can be added to the surface as a mask for etching, with a thickness of 100 nanometers to 300 nanometers;

[0209] f. Ti&Pt / Ti&Mo deposition by magnetron sputtering / evaporation coating and other processes, with the thickness of deposited Ti being 10 nm to 40 nm and the thickness of deposited Pt or Mo being 150 nm to 350 nm;

[0210] g. Depositing silicon oxide by plasma enhanced chemical vapor deposition (PECVD) or sub-atmospheric pressure chemical vapor deposition (SACVD) to improve passivation performance, with a thickness of 2000 nanometers to 4000 nanometers;

[0211] h. Etch the pad to make a wet etch or deep silicon mask window;

[0212] i. Use a wet solution, such as potassium hydroxide (KOH) or tetramethylammonium hydroxide (TMAH) for wet etching; or use dry etching to make a sample concentration device.

[0213] It should be noted that, between step b and step c, the manufacturing method may further include:

[0214] A layer of LPCVD silicon nitride may be added to the surface of the first silicon oxide layer on the upper surface of the silicon wafer as a mask for wet etching, with a thickness of 100 nanometers to 300 nanometers.

[0215] The thickness of the surface silicon is 5 to 50 microns, and the thickness of the silicon oxide is 500 to 3000 nanometers, which can achieve a better dew point temperature distribution effect.

[0216] The size of the wet etch window is 280 microns to 2500 microns.

[0217] It will be easily understood by those skilled in the art that the above is only a preferred embodiment of the implementation mode of the present application and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A sample concentration method, characterized in that: include: adjusting the temperature of the sample in the sample holding tank so that when the actual liquid level of the sample drops to the target liquid level, the actual liquid level is controlled to remain at the target liquid level; The target liquid level is the liquid level in the sample holding tank corresponding to the target volume of the sample, and the target volume is determined according to the initial volume of the sample and a preset concentration multiple.

2. The sample concentration method according to claim 1, characterized in that: The controlling the actual liquid level to be maintained at the target liquid level comprises: The temperature at the actual liquid level of the sample is made equal to the dew point temperature at the location of the sample holding tank.

3. The sample concentration method according to claim 1, characterized in that: The controlling the actual liquid level to be maintained at the target liquid level comprises: The vapor partial pressure at the location of the sample holding groove is made equal to the saturated vapor pressure.

4. The sample concentration method according to claim 1, characterized in that: The controlling the actual liquid level to be maintained at the target liquid level comprises: The relative humidity at the location of the sample holding slot is made equal to the saturated humidity.

5. The sample concentration method according to any one of claims 1 to 4, characterized in that: Regulating the temperature of a sample in a sample holding tank includes: The temperature of the sample located between the initial liquid level and the target liquid level is greater than the dew point temperature, the temperature of the sample located at the target liquid level is equal to the dew point temperature, and the temperature of the sample located below the target liquid level is less than the dew point temperature; wherein the initial liquid level is the liquid level in the sample holding tank corresponding to the initial volume of the sample.

6. The sample concentration method according to claim 5, characterized in that: Regulating the temperature of a sample in a sample holding tank includes: The temperature of the sample concentration area of ​​the side wall is adjusted by a temperature control module disposed on the side wall of the sample holding tank; wherein the initial liquid level and the target liquid level are both located in the sample concentration area.

7. The sample concentration method according to claim 6, characterized in that: By means of a temperature control module disposed on the side wall of the sample holding tank, the temperature of the sample concentration area of ​​the side wall is adjusted, including: heating a first position of the sample concentration region by a heating component of the temperature control module so that the temperature of the first position is greater than the dew point temperature; and A second position in the sample concentration region which is lower than the first position is cooled by a cooling component of the temperature control module, so that the temperature of the second position is lower than the dew point temperature.

8. The sample concentration method according to claim 7, characterized in that: When the side wall includes a first variable temperature region made of a heat conductive material, and the sample concentration region is located within the first variable temperature region, the sample concentration method further includes: The heating component heats the upper end of the first temperature-variable region, and the cooling component cools the lower end of the first temperature-variable region, so that the temperature at the target liquid level is equal to the dew point temperature.

9. The sample concentration method according to claim 8, characterized in that: The thermal conductivity of the first variable temperature region is greater than 50 W / (m K).

10. The sample concentration method according to claim 8, characterized in that: The material of the first variable temperature region is selected from one of ceramics, silicon, metal, silicon carbide and aluminum nitride.

11. The sample concentration method according to claim 7, characterized in that: When the side wall includes a first variable temperature region, an intermediate region, and a second variable temperature region stacked in sequence, and the thermal conductivity of the intermediate region is lower than the thermal conductivity of the first variable temperature region and the thermal conductivity of the second variable temperature region, the sample concentration method further includes: The heating component heats the first variable temperature region, and the cooling component cools the second variable temperature region, so that the temperature of the intermediate region is equal to the dew point temperature.

12. The sample concentration method according to claim 11, characterized in that: The material of the first variable temperature region is selected from one of ceramics, silicon, metal, silicon carbide, and aluminum nitride; and / or The material of the middle region is selected from one of silicon oxide, porous silicon, silicon nitride and polyimide; and / or The material of the second variable temperature zone is selected from one of ceramics, silicon, metal, silicon carbide and aluminum nitride.

13. The sample concentration method according to claim 11, characterized in that: The thickness of the middle region is 500 nanometers to 3000 nanometers.

14. The sample concentration method according to claim 13, characterized in that: The thickness of the first variable temperature region is 50 micrometers to 2000 micrometers; and / or The thickness of the second variable temperature region is 5 micrometers to 200 micrometers.

15. The sample concentration method according to any one of claims 1 to 4, characterized in that: The sample holding tank is manufactured by a MEMS manufacturing process.

16. The sample concentration method according to any one of claims 1 to 4, characterized in that: The method further comprises: detecting an actual liquid level of the sample; It is determined whether the actual liquid level is at the target liquid level.

17. The sample concentration method according to any one of claims 1 to 4, characterized in that: The method further comprises: During the concentration of the sample, the covering component forms a closed evaporation chamber above the sample holding groove.

18. The sample concentration method according to claim 17, characterized in that: The method further comprises: During the concentration of the sample, the humidity control module controls the humidity of the evaporation chamber.

19. A detection method, characterized in that: The sample concentration method according to any one of claims 1 to 18, wherein the detection method further comprises: After the sample is concentrated, the light detection component detects the emitted light or absorbed light of the sample in the sample holding tank.

20. The detection method according to claim 19, characterized in that: After the sample concentration is completed, the optical detection component performs optical detection on the sample in the sample holding tank, including: A light source generates light that is irradiated into the sample; The detector receives a light signal emitted from the sample or absorbed by the sample, and generates a detection signal in response to the received light signal; The data analysis system receives the detection signal from the detector and generates a detection result in response to the detection signal.

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