Mass spectrometer sample bottle for detecting saliva

Abstract

The utility model relates to the technical field of sample processing containers, in particular to a mass spectrometer sample bottle for detecting saliva. Comprising a bottle body, the top end of the bottle body is provided with a bottle opening, and an inner cavity bottom is arranged in the bottom end of the bottle body; the inner cavity bottom comprises a conical part, and the inner wall of the conical part shrinks from the lower section of the inner cavity of the bottle body to the direction of the central axis of the bottom of the bottle body to form a collecting and precipitating area; the micro boss is arranged in the central area of the bottom of the conical part and protrudes upwards, the micro boss is provided with a top surface, and the top surface is higher than the bottommost position of the collecting and precipitating area of the conical part; the utility model provides a saliva sample bottle for a mass spectrometer, which can solve the problem that when a general sample bottle is used for treating viscous and particulate matter-containing biological samples such as saliva, the saliva cannot be separated from the sample bottle. And due to the unreasonable structural design of the bottom of the inner cavity, the sample suction is incomplete, the liquid residual quantity is large, and bottom settled particles are easily sucked together, so that the analysis is interfered and the instrument is possibly blocked.

Description

Technical Field

[0001] This utility model relates to the field of sample processing container technology, and in particular to a mass spectrometer sample bottle for detecting saliva. Background Technology

[0002] In modern biochemical analysis, especially in metabolomics, proteomics, drug metabolism research, and clinical diagnostic applications based on high-performance liquid chromatography-mass spectrometry (HPLC-MS), automated, high-throughput sample preparation and analysis are crucial.

[0003] Saliva, as a non-invasive and easily collected biological sample, is increasingly favored by researchers.

[0004] However, saliva samples have different physical properties than pure solvents or simple solutions. For example, they usually have high viscosity and often contain a certain amount of endogenous solid particles, such as sloughed oral epithelial cells, undigested food residue particles, bacterial aggregates, or tiny crystals (stones, etc.) formed by certain metabolic products.

[0005] Currently, sample vials widely used in automated mass spectrometry systems are mostly small-volume containers with standard external dimensions. Their internal bottom designs vary, commonly including flat bottoms, round bottoms, or gently sloping conical bottoms. When using these traditional, general-purpose sample vials to process special biological samples such as saliva, the following technical problems often arise due to their structural defects:

[0006] 1. Incomplete sample aspiration and waste: Due to the viscosity of saliva, it is not easy for it to flow and collect completely and smoothly to the bottom center in traditional sample vials. Especially when the bottom structure is not conducive to effective liquid collection (e.g., a flat bottom design results in a large liquid spreading area, or a gently sloping conical bottom has poor guiding effect on high-viscosity liquids), a considerable portion of the sample liquid will remain on the vial wall or bottom edge, making it difficult for the autosampler to aspirate completely, resulting in sample waste.

[0007] This problem is particularly prominent in situations where the sample size is extremely limited, difficult to obtain (such as pediatric samples or certain animal experimental samples), or very precious (such as clinical rare specimens or samples collected at specific time points). It not only reduces the actual utilization rate of the samples, but may even affect the accuracy of subsequent analyses or prevent the completion of all predetermined testing items due to insufficient sample size.

[0008] 2. Impaired accuracy and stability of analytical results: Endogenous particulate matter in saliva gradually settles and accumulates at the bottom of the sample vial due to gravity while it is placed in the autosampler's sample tray awaiting analysis. When the autosampler needle descends to aspirate the sample, if the aspiration point is improperly set (e.g., too low), or if the bottom structure of the sample vial fails to effectively separate the particulate matter from the supernatant, these settled particles are easily aspirated along with the liquid sample. Once these aspirated particles enter the sophisticated mass spectrometer's injection system (such as the injection valve, quantitative loop, connecting capillary, ion source needle, etc.) or the chromatographic column, a series of negative effects will occur:

[0009] Signal interference: Particulate matter itself may directly scatter or absorb the analytical signal, or interfering substances adsorbed on its surface may be eluted out, resulting in false peaks, increased baseline noise, suppression or enhancement of the target analyte signal, etc., which seriously affect the accuracy, precision and reliability of the analytical results.

[0010] Cross-contamination: Particulate matter may slowly release substances it contains or adsorbs during subsequent sample injection analysis, causing cross-contamination of subsequent samples.

[0011] 3. It also easily leads to a high risk of blockage in the instrument's precision components, increasing maintenance costs and downtime:

[0012] Because inhaled solid particles, especially large, irregularly shaped, or sticky particles, pose a high risk of clogging the narrow flow paths of delicate components in mass spectrometer or chromatographic systems. For example, the tip of the autosampler needle, the connecting capillary (especially those with inner diameters in the tens to hundreds of micrometers range), the tip of the electrospray ionization (ESI) needle, and the inlet sieve plate or column packing of the high-performance liquid chromatography (HPLC) column are all highly susceptible to clogging. Once clogging occurs, it not only interrupts the current analytical sequence but also requires significant time and manpower for troubleshooting, component cleaning (such as ultrasonic cleaning, solvent rinsing, and backflushing), or replacement. This significantly increases instrument maintenance costs (including labor and spare parts costs), prolongs unplanned downtime, reduces laboratory analytical efficiency, and the repeated clogging and cleaning processes can accelerate the aging and damage of these expensive and delicate components, shortening their lifespan. Utility Model Content

[0013] The main objective of this invention is to overcome the shortcomings of existing general-purpose sample vials when processing viscous biological samples such as saliva containing particulate matter. These shortcomings stem from the unreasonable design of the bottom structure of the inner cavity, leading to incomplete sample aspiration, large amounts of residual liquid, and the easy inhalation of bottom-sedimentary particles that interfere with analysis and may clog the instrument. This invention provides a saliva sample vial for mass spectrometry that solves the aforementioned problems.

[0014] To achieve the above objectives, the core technical solution adopted by this utility model is as follows:

[0015] A mass spectrometer sample vial for detecting saliva includes:

[0016] The bottle body has a bottle mouth at the top and an inner cavity at the bottom.

[0017] The inner floor includes:

[0018] The conical section, with its inner wall tapering from the lower part of the bottle's interior towards the central axis at the bottom, forms a sedimentation area; and

[0019] A micro-protrusion is provided at the bottom center region of the cone and protrudes upward. The micro-protrusion has a top surface that is higher than the bottom of the sedimentation area of ​​the cone.

[0020] Furthermore, the angle α formed by the generatrix of the side wall of the conical part and the central axis of the bottle ranges from 15 degrees to 45 degrees.

[0021] Furthermore, the included angle α ranges from 20 degrees to 30 degrees.

[0022] Furthermore, the vertical distance from the inflection point of the inner wall at the beginning of the cone to the lowest point of the cone tip is the height H, and its diameter at the bottom opening is D, and H / D≥2.

[0023] Furthermore, the top surface of the micro-boss is a downwardly concave curved surface.

[0024] Furthermore, the vertical distance from the lowest convergence point of the cone to the top surface of the micro-boss is the height h of the micro-boss, and h ranges from 2 mm to 8 mm.

[0025] Furthermore, the height h ranges from 3 mm to 5 mm.

[0026] Furthermore, the tapered portion and the boss are connected by a rounded transition.

[0027] Furthermore, the diameter of the top surface of the micro-protrusion is d, and the inner diameter of the bottle's inner cavity at the corresponding height is d1, where d1 / 2 > d > d1 / 5.

[0028] Furthermore, if the top surface of the micro boss is a curved structure that is concave inward and downward, then the depth of the concavity is half of the height h of the micro boss. Beneficial effects

[0029] Compared with conventional sample vials of the prior art, the saliva sample vial for mass spectrometers of this invention, through its unique inner bottom structure design, especially the synergistic effect of the conical part and the micro-protrusion, brings the following significant advantages:

[0030] Significantly improves the aspiration efficiency and recovery rate of viscous samples: The conical section's inward-contracting structure, especially when it has a suitable steepness, can more effectively guide and collect highly viscous saliva samples towards the central region at the bottom of the inner cavity using gravity, minimizing the amount of sample liquid remaining on the inner wall of the bottle (particularly the bottom region). This directly improves the actual utilization and recovery rate of the sample, which is particularly important for analyses with small or valuable sample volumes, contributing to more accurate and reliable quantitative analysis results.

[0031] Effective separation and avoidance of bottom-sedimentary particles, improving analytical accuracy: The collection and sedimentation area formed by the conical section effectively collects and confines particles settled by gravity in the sample to the recessed area surrounding the micro-protrusions. The upward-protruding structure of the micro-protrusions ensures that their top surface (i.e., the theoretical lowest aspiration point of the autosampler) is always higher than the bottom of the particle sedimentation area. Therefore, when the autosampler aspirates the sample, it primarily contacts the relatively pure supernatant located above or near the top surface of the micro-protrusions, effectively avoiding or significantly reducing the probability of aspirating bottom-sedimentary particles. This directly reduces the interference of particulate matter on the mass spectrometry signal (such as ion suppression effects, false peaks, baseline noise, etc.), significantly improving the accuracy, precision, and overall data quality of the analytical results.

[0032] Effectively protects the precision components of mass spectrometry instruments, extends maintenance cycles, and reduces operating costs: By significantly reducing the intake of solid particles, the sample vial structure of this invention effectively reduces the risk of blockage or contamination of precision components in the mass spectrometer's sample introduction system (such as injection needles, connecting capillaries, injection valves, ion source nozzles, etc.) and the flow path of the liquid chromatography column. This not only directly improves the stability and reliability of instrument operation and reduces unplanned downtime and related troubleshooting work caused by blockage or contamination, but also helps extend the service life of these expensive precision components, thereby reducing the frequency of instrument maintenance and overall operating costs.

[0033] Optimized micro-sample handling and effective reduction of dead volume: The conical structure itself facilitates liquid collection in a smaller bottom area, thereby reducing the liquid spreading area. This is beneficial for reducing the dead volume of the sample vial (i.e., the amount of residual liquid that cannot be effectively aspirated by the injection needle). Combined with the micro-protrusions for further liquid concentration and precise elevation of the aspiration point, this sample vial structure is particularly suitable for scenarios requiring analysis of extremely small amounts (e.g., tens of microliters or even less) of saliva samples, maximizing the use of limited sample resources. Attached Figure Description

[0034] To enable those skilled in the art to more clearly and comprehensively understand the technical solution of this utility model, the preferred embodiments of this utility model will be described in detail below with reference to the accompanying drawings. It should be noted that the accompanying drawings are for illustrative purposes only and are not intended to limit the scope of protection of this utility model. In the accompanying drawings:

[0035] Figure 1 yes Figure 1 This is a longitudinal sectional view of the overall structure of a saliva sample bottle according to an embodiment of the present invention.

[0036] Figure 2 yes Figure 1 A magnified structural diagram of section A (i.e., the bottom of the inner cavity).

[0037] Figure 3 This is a schematic diagram showing the state of the saliva sample bottle of this utility model when used in conjunction with an exemplary standard bottle cap.

[0038] In the above figures, the same reference numerals denote parts that have the same or similar functions. The names of the parts represented by each reference numeral are as follows:

[0039] 1-Bottle body; 11-Bottle mouth; 2-Inner cavity bottom; 21-Conical part; 22-Miniature boss; 221-Top surface; 3-Bottle cap; α-Angle between the generatrix of the side wall of the conical part and the central axis of the bottle body; H-Effective converging height of the conical part; D-Diameter of the bottom opening of the conical part; h-Height of the miniature boss; d-Diameter of the top surface of the miniature boss; d1-Inner diameter of the inner cavity of the bottle at the height of the corresponding boss top surface. Detailed Implementation

[0040] The present invention will now be described in detail with reference to the accompanying drawings:

[0041] To make the objectives, technical solutions, and advantages of this utility model clearer, several preferred embodiments of this utility model will be described in detail below with reference to the accompanying drawings. It should be understood that the embodiments described herein are merely for explaining this utility model and do not constitute any limitation on its scope of protection. Any modifications, equivalent substitutions, or improvements made based on the spirit and principles of this utility model should be included within the scope of protection of this utility model. Example

[0042] Reference Figure 1 , Figure 2 and Figure 3 This embodiment discloses a saliva sample vial for use in a mass spectrometer. The core structure of this sample vial comprises a vial body 1, with a vial opening 11 at the top for connection with a vial cap 3 (e.g., ...). Figure 3As shown, this is a schematic structure; the bottle cap typically contains a puncture-resistant septum to seal the sample. Crucially, the bottom of the bottle body 1 has a specially designed inner cavity 2.

[0043] The structure of the inner cavity bottom 2 is the key difference between this invention and existing technologies. Specifically, it includes a conical portion 21 and a micro-protrusion 22. The inner wall of the conical portion 21 begins at the lower section of the inner cavity of the bottle body 1 (i.e., the area where the straight wall of the bottle body transitions downwards) and smoothly and continuously tapers towards the central axis of the bottom of the bottle body 1, thereby forming a funnel-shaped sedimentation area at the bottom of the bottle. The main function of this sedimentation area is to guide the liquid sample towards the center using gravity and to provide a space for the sedimentation and accumulation of any solid particles that may be present in the sample.

[0044] Next, the micro-protrusion 22 is located at the bottom center region of the conical portion 21, which is the theoretical point of convergence of the cone tip, and protrudes upward from this point (i.e., towards the bottle neck 11). This micro-protrusion 22 has a top surface 221, the height of which is precisely designed to always be higher than the bottom of the sedimentation area formed by the conical portion 21. This structural layout ensures that when the autosampler aspirates a sample, the lowest point of contact of its tip, or the effective sampling area, is located above the area where particulate matter may accumulate.

[0045] In order for the conical portion 21 to effectively collect viscous liquids and guide the sedimentation of particulate matter, its geometry is specifically defined. Specifically, the angle α formed by the generatrix of the sidewall of the conical portion 21 (i.e., the projection of the straight line constituting the conical surface onto a cross-section passing through the central axis) and the central axis of the bottle body 1 (this angle α is also often referred to as the half-cone angle, such as...) Figure 1 The angle range (as shown) is set from 15 to 45 degrees. This angle range is designed to ensure that the cone has enough steepness to promote liquid flow and particle concentration at the bottom, while avoiding problems such as an excessively narrow bottom or an excessively long bottle due to an angle that is too small, which may lead to manufacturing difficulties, as well as problems such as a reduced collection effect under gravity due to an angle that is too large.

[0046] In a preferred structural design, the included angle α is further optimized to a range of 20 to 30 degrees. For example, specific angle values ​​such as 22 degrees, 25 degrees, or 28 degrees can be selected. Practice has shown that cone angles within this range provide more ideal liquid collection efficiency and particulate matter separation for common saliva samples, while also ensuring structural stability and the feasibility of the manufacturing process.

[0047] In addition to the limitation of the cone angle α, the steepness of the cone portion 21 can be further characterized by the ratio of its effective converging height H to the theoretical bottom opening diameter D. Here, the height H refers to the vertical distance from the inflection point of the inner wall formed from the cone portion 21 (i.e., the precise starting point where the inner wall of the bottle turns from an approximately vertical straight wall section to a conical contraction) to its theoretical lowest point of the cone tip (i.e., the lowest point formed by the intersection of the extended conical inner walls without considering the presence of the central micro-protrusion 22). The bottom opening diameter D refers to the opening diameter at the lowest point of the cone portion. This invention requires that the ratio of these two satisfy H / D≥2. This condition ensures that the cone portion 21 has sufficient relative depth, thereby significantly enhancing its converging capacity.

[0048] Regarding the structural details of the micro-protrusion 22, its overall shape can be diverse, as long as it can protrude upwards and provide a sampling platform higher than the particle settling zone. In this embodiment, the top surface of the micro-protrusion 22 needs to be designed to be concave downwards, for example, a hemispherical or semi-elliptical surface; these shapes each have their advantages: hemispherical and semi-elliptical top surfaces may utilize surface tension to further collect residual liquid when processing extremely small amounts of liquid; and both shapes have the lowest point at the center, ensuring that the injection needle can be inserted to the lowest point of the top concavity during insertion, completely aspirating the sample liquid. To ensure that liquid and particles can flow smoothly from the inner wall of the conical portion 21 to and settle in the grooves around the micro-protrusion 22, the sidewall of the micro-protrusion 22 and the conical surface of the conical portion 21 are preferably designed with a smooth transition connection structure, such as a rounded corner transition, to avoid forming dead corners, steps, or sharp edges that may trap liquid or particles, and also to avoid damaging the injection needle and other instruments.

[0049] The height h of the micro-protrusion 22 is a key dimensional parameter that directly affects the particulate matter separation effect and the dead volume of the sample vial. This height h is defined as the vertical distance from the lowest point of the conical portion 21 to the top surface 221 of the micro-protrusion 22. In this invention, the height h is set to a range of 2 mm to 8 mm. This range is determined based on a comprehensive consideration of the thickness of the sediment layer that may form after settling particulate matter (such as oral epithelial cells, food particles, etc.) in common saliva samples has settled.

[0050] In a more optimized design, the height h is further precisely defined as 2 mm to 5 mm. For example, a height of 3 mm, 4 mm, or 5 mm can be selected. This height range has good universality for particulate matter sedimentation layers in most saliva samples, effectively avoiding the inhalation of particles while minimizing the adverse effects on dead volume, and also avoiding excessive height resulting in insufficient saliva sample on the top surface.

[0051] The top surface 221 is designed as a curved surface structure that depresses inward and downward, for example, forming a tiny pit, which is hemispherical, semi-elliptical or shallow dish-shaped. This depressed structure may utilize the surface tension effect of the liquid to further collect the last few microliters or even less amount of liquid remaining on the top surface of the boss into the lowest point at the center of the depression, which can improve trace analysis or ultra-trace sample processing with extremely high sample recovery rates.

[0052] To ensure that the top surface 221 of the micro-boss 22 can provide a stable sample aspiration platform and does not overly occupy the bottom center space to affect the collection function of the conical part 21, its size also needs to be reasonably set. The diameter of the top surface 221 of the micro-boss 22 (for a non-circular top surface, it refers to its equivalent characteristic width) is defined as d. At the same time, the inner diameter of the inner cavity of the bottle body 1 at the height corresponding to the top surface 221 of the boss is defined as d1. The present utility model requires that the value of d is greater than one-fifth of d1 and less than one-half of d1, that is, it satisfies the relationship of d1 / 5 < d < d1 / 2. This size ratio ensures that the top surface of the boss has sufficient area to stably carry and position the sampling needle tip, while avoiding reducing the effective groove volume for collecting liquid and accommodating particulate matter or significantly increasing the dead volume of the sample bottle due to the overly large boss.

[0053] Furthermore, if the top surface 221 of the micro-boss 22 is designed as a curved surface structure that depresses inward and downward, specific considerations are also given to the depth of this depression. In this case, the depth of the depression (i.e., the vertical distance from the edge of the depression to the lowest point of the depression) is preferably designed to be one-half of the height h of the micro-boss 22 itself (i.e., h / 2). Such a proportional relationship aims to ensure that the depression has sufficient depth to effectively collect the residual liquid, but not so deep as to cause the structure to be too complex, difficult to clean, or cause additional trouble to the precise positioning of the sampling needle.

[0054] The overall structure of the bottle body 1, including its external contour dimensions and the specifications of the bottle mouth 11, is designed to conform to the general standards of existing mainstream mass spectrometer auto-sampling systems. The bottle mouth 11 can be adapted to various standard types of bottle caps 3, such as 8-thread caps, short-neck thread caps or press caps, etc., and these bottle caps usually have a central septum that can be punctured by an auto-sampling needle.

[0055] Brief description of the working principle and usage method:

[0056] When the user adds the collected saliva sample into the sample bottle of the present utility model through tools such as a pipette, due to the centripetal guiding effect of the conical part 21 in the inner cavity bottom 2, even highly viscous saliva will flow more effectively and collect in the annular transition groove area around the central micro-boss 22 under the action of gravity.

[0057] If the saliva contains easily settling particles, these particles will gradually settle due to gravity while the sample vial is placed in the sample tray of the autosampler and awaiting analysis. They will eventually aggregate and be contained in the aforementioned sedimentation area formed by the cone-shaped portion 21 and located around the micro-protrusion 22.

[0058] Since the micro-protrusions 22 have a specific height h (e.g., 3-5 mm), their top surface 221 will be significantly higher than the upper interface of the sediment layer formed by these sedimented particles.

[0059] When the autosampler performs a sample aspiration operation, controlling the injection needle to descend to the corresponding aspiration depth ensures that the actual lowest aspiration position of the autosampler needle tip is precisely controlled within the recessed area above the top surface 221 of the micro-protrusion 22.

[0060] Therefore, the autosampler needle aspirates the relatively pure saliva supernatant above the particle sedimentation layer, effectively avoiding or greatly reducing the risk of aspirating bottom sediment particles. This not only ensures the accuracy and reliability of the analytical data but also protects the precision components of the mass spectrometer and its coupled systems (such as liquid chromatography) from particulate contamination and clogging. Simultaneously, due to the effective collecting action of the cone 21, even trace amounts of sample can be concentrated in the central region for aspirator application, improving sample utilization.

[0061] In summary, this invention, through an innovative design of the bottom structure of the sample vial's inner cavity—specifically, a combination of a conical section, a central micro-protrusion, and a concave top surface structure—and by optimizing and limiting the geometry, dimensional parameters, and interrelationships of each key component, successfully solves a series of problems faced by existing technologies in processing viscous samples such as saliva containing particulate matter, including low sample recovery rates, easy inhalation of particulate matter interfering with analysis, and damage to instruments. It provides a simple and practical technical solution for achieving high-throughput, high-precision, and high-stability automated saliva sample analysis.

[0062] Finally, it should be emphasized that the embodiments described above are merely illustrative of the technical concept and preferred implementation of this utility model, and are not intended to exhaustively describe or limit the scope of protection of this utility model. Any person skilled in the art, after understanding the spirit and core technical solution of this utility model, may make various modifications, equivalent substitutions, or improvements based on the content disclosed in this utility model, without departing from its basic principles. These obvious modifications or substitutions should all be considered to be included within the scope of protection claimed by this utility model.

Claims

1. A mass spectrometer sample vial for detecting saliva, characterized in that, include: Bottle body (1), the top of the bottle body (1) is provided with a bottle mouth (11), and the bottom of the bottle body (1) is provided with an inner cavity bottom (2); The inner cavity bottom (2) includes: The conical part (21) has an inner wall that tapers from the lower part of the inner cavity of the bottle body (1) toward the central axis of the bottom of the bottle body (1) to form a sedimentation area. as well as A micro-protrusion (22) is provided at the bottom center region of the cone (21) and protrudes upward. The micro-protrusion (22) has a top surface (221) which is higher than the bottom of the sedimentation area of ​​the cone (21).

2. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, The angle α formed by the generatrix of the side wall of the conical part (21) and the central axis of the bottle body (1) ranges from 15 degrees to 45 degrees.

3. The mass spectrometer sample vial for detecting saliva according to claim 2, characterized in that, The included angle α ranges from 20 degrees to 30 degrees.

4. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, The vertical distance from the inflection point of the inner wall of the conical part (21) to the lowest point of the cone tip is the height H, and the diameter of its bottom opening is D, and H / D≥2.

5. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, The top surface of the micro boss (22) is a downwardly concave curved surface.

6. The mass spectrometer sample vial for detecting saliva according to claim 1 or 5, characterized in that, The vertical distance from the lowest convergence point of the tapered portion (21) to the top surface (221) of the micro-boss (22) is the height h of the micro-boss (22), and the range of h is 2 mm to 8 mm.

7. The mass spectrometer sample vial for detecting saliva according to claim 6, characterized in that, The height h ranges from 3 mm to 5 mm.

8. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, The tapered portion and the boss are connected by a rounded corner transition.

9. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, The diameter of the top surface (221) of the micro boss (22) is d, and the inner diameter of the inner cavity of the bottle body (1) at the corresponding height of the top surface is d1, wherein d1 / 2 > d > d1 / 5.

10. The mass spectrometer sample vial for detecting saliva according to claim 1, characterized in that, If the top surface (221) of the micro boss (22) is a curved surface structure that is concave inward and downward, then the depth of the concavity is half of the height h of the micro boss (22).

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