CN117871178B - Quantitative absorption micro sampling device, storage platform and storage system - Google Patents
Quantitative absorption micro sampling device, storage platform and storage system Download PDFInfo
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Classifications
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
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Abstract
The invention provides a quantitative absorption microsampling device, a storage platform and a storage system, which belong to the technical field of dry blood spot sampling. The quantitative absorption microsampling device provides a microenvironment which is not influenced by the outside for forming and storing the dried blood spot sample, can store the backup dried blood spot sample in the same dry environment, and can continuously utilize the backup sample for detection when the detection sample has a problem, so that the normal development of the detection is ensured; the identical environment can ensure the consistency of the components of the detection sample and the backup sample, the detection results are not different due to the difference of the dry blood spot samples, and the accuracy of the detection results is ensured.
Description
Technical Field
The invention relates to the technical field of dry blood spot sampling, in particular to a quantitative absorption microsampling device, a storage platform and a storage system.
Background
The Dry Blood Spot (DBS) technique is a sample collection technique and sample morphology, also known as dry Blood spots or dry Blood sheets. The technology is to drop the fingertip blood or the foot blood of a subject on a sample collecting card, and dry the blood spots formed at room temperature. The technology is widely applied to clinical examination, and when in clinical examination, a dry blood sheet with specific specification is cut as a sample according to the requirement of an examination method and is extracted and detected, and various back-end detection devices can be carried, wherein the detection comprises cholesterol, C-reactive protein, glycosylated hemoglobin, cytokines, genetic materials and the like, and the technology is applied to the fields of neonatal disease screening, HIV/HCV screening, stimulant detection, accurate medical treatment and the like.
When the dry blood spots are collected in the prior art, a blood micro hemostix is often used for collecting blood, then the blood collected by the hemostix is transferred to a sample collection card for drying treatment, and the dry blood spots are required to be effectively stored after the drying treatment. In order to ensure the accuracy of the detection result, the formation and storage environment of the dried blood spots are guaranteed, the dried blood spots are required to be isolated from the environment, the conventional technology is difficult to meet the requirements, and the acquisition card is often exposed to the air and is easy to pollute.
CN212341118U discloses a quantitative collection device for dried blood spots, which comprises a sample collection tube, a sample collection filter paper and a quantitative collection tube, wherein the quantitative collection tube is fixed in the closable sample collection tube after collecting blood, the filter paper is dried in the sample collection tube after absorbing blood in the quantitative collection tube, and the influence of the environment on the dried blood spots can be greatly reduced because the filter paper is protected by the sample collection tube during absorption, drying, preservation and transportation.
The dried blood spot collecting tool comprising the device is directly dried after single-tube collection, and the obtained dried blood spots are one part, and once the dried blood spots are damaged in the later period or are unavailable due to other accidents, the dried blood spots cannot be detected to obtain a detection result, so that unavoidable losses are caused.
Disclosure of Invention
In order to prevent the occurrence of the condition that detection cannot be performed due to unexpected situations such as damage of dry blood spots, the invention provides a quantitative absorption microsampling device, a storage platform and a storage system, which can store a plurality of dry blood spot samples in the same environment, ensure that the normal operation of the later detection is not influenced by the damage of a single dry blood spot, and simultaneously ensure that the components and the properties of all the dry blood spot samples are consistent due to the storage in the same environment, and the detection results are not different due to the difference of the dry blood spot samples.
The invention provides a quantitative absorption microsampling device, which comprises a cover body and a box body, wherein the cover body is matched with the box body and connected to form a closed space to isolate an external environment, a plurality of quantitative blood collection tubes which extend towards the box body and are used for quantitatively collecting microsamples are fixed at the bottom of the cover body, sample carriers which are equal to the quantitative blood collection tubes in number and are opposite to each other one by one and can absorb the blood samples are fixed in the box body, the bottom ends of the quantitative blood collection tubes are contacted with the sample carriers, and the sample carriers absorb the quantitative blood samples in the quantitative blood collection tubes and are dried in the same environment in the box body to form a plurality of dried blood spot samples comprising detection samples and backup samples;
the box body comprises a bottom box and a perspective part for observing the formation of a dried blood spot sample, wherein the perspective part comprises an upper clamping ring, a lower clamping ring and a perspective ring window positioned between the upper clamping ring and the lower clamping ring, the upper clamping ring is detachably connected with the cover body, and the lower clamping ring is detachably connected with the bottom box;
The sample carrier is placed on a support of a perspective ring window which is positioned in the bottom box and is close to the perspective part, and the perspective part is connected with the bottom box and then respectively fixes the support and the sample carrier so as to limit the positions of the support and the sample carrier.
Further, the cover body comprises an upper cover and an outer clamping ring detachably connected with the upper clamping ring of the perspective part, and the quantitative blood collection tube is fixed at the bottom of the upper cover.
All fix the bottom at the upper cover with a plurality of ration heparin tubes, handheld upper cover removes ration heparin tube when using, guarantees the stability and the security of heparin tube, and handheld upper cover can realize the sampling of a plurality of ration heparin tubes for blood sample collection's progress. The detachable connection mode of the upper cover and the perspective part is convenient for removing the perspective part when the blood sample needs to be collected, and the sampling is not affected.
Further, a plurality of fixed clamping grooves are formed in the bottom of the upper cover, the quantitative blood collection tube comprises a tube body and a connecting portion, and the connecting portion is inserted into the fixed clamping grooves to be clamped with the upper cover.
In the above-mentioned setting, fixed draw-in groove can firmly fix the connecting portion of ration heparin tube, make the ration heparin tube reliably fix in the upper cover bottom, ensure that the ration heparin tube can not drop or rock in transportation, storage or use, in addition, also be convenient for dismantle the ration heparin tube from the upper cover, only need aim at fixed draw-in groove with connecting portion and insert, can accomplish fixedly, also only need extract the ration heparin tube during the dismantlement can, so that install or change the ration heparin tube of different capacities as required, the commonality and the flexibility of device have been improved.
Further, the support includes the extension board of placing on the platform of the internal surface of end box and is located the extension board upper surface and the interval sets up and with the corresponding support ring of ration heparin tube, the sample carrier is placed the support ring, the internal surface of perspective portion is provided with outstanding clamp plate, the clamp plate compresses tightly the edge and the support ring of sample carrier respectively and restricts the removal of sample carrier and support.
After the perspective part is connected with the bottom box, the pressing plate of the perspective part can directly compress the sample carrier and the bracket, so that the positions of the sample carrier and the bracket are fixed, other fixing modes are not needed, the assembly of the sampling device is convenient, and the dried blood spot sample is taken out from the sampling device during detection.
Further, the upper surface of the support plate is provided with a partition plate for partitioning the spaced support rings, and the height of the partition plate is larger than that of the support rings.
Because the formation of each dry blood spot sample needs mutually independent, guarantees the accuracy of absorption blood sample volume, and the setting of division board can avoid adjacent sample carrier to influence each other at the in-process of absorption blood sample, has prevented the crossing between the dry blood spot sample, in addition, the setting of division board is also convenient for the installation and the takeout of support.
Further, the sample carrier is a modified sample carrier with improved stability prepared by the following method:
dissolving at least one protective agent in methanol water to obtain a treatment liquid;
Step two, soaking an original sample carrier in the treatment liquid for 0.5-2 min;
and thirdly, taking out the infiltrated sample carrier, and drying the sample carrier in a drying oven, wherein the drying temperature is 30-40 ℃ and the drying time is 3-6 hours, so that the sample carrier is completely dried.
Further, the sample carrier is a sample carrier containing stable isotope internal standard for improving the accuracy and reliability of a dry blood spot sample detection result, which is obtained by adopting the following method:
firstly, mixing methanol and water in a certain proportion to obtain a diluent; diluting and dissolving an internal standard to obtain stock solution; mixing the stock solution and the diluent according to a certain proportion to obtain an internal standard treatment solution meeting the concentration requirement;
And step two, adding an internal standard treatment liquid to the original sample carrier and drying.
In a second aspect, the present invention provides a storage platform for storing a quantitative absorption micro-sampling device, including a platform body, wherein at least one placement groove is provided on an upper surface of the platform body, and the placement groove accommodates the quantitative absorption micro-sampling device and stabilizes the quantitative absorption micro-sampling device.
In a third aspect, the present invention provides a storage system comprising a quantitative absorption microsampling device storage platform, the quantitative absorption microsampling device being placed in a placement groove of the storage platform.
According to the quantitative absorption micro-sampling device, the storage platform and the storage system, a micro environment which is not influenced by the outside is provided for the formation and storage of the dry blood spot samples, a plurality of dry blood spot samples are synchronously formed in the same environment after the quantitative collection of the blood samples, the requirements of detection and backup are met, even if the detection samples cannot be detected due to damage of unexpected situations, the backup samples can still be used for detection, and the detection samples and the backup samples are formed and stored in the same environment, so that the accuracy of detection results can be ensured without resampling, and the time and cost of resampling are greatly saved, and the risk of inaccurate results possibly existing in resampling is reduced; in addition, the invention adopts the modified sample carrier to improve the stability of the components to be detected in the sample, so that the detection result is more close to the real situation, and in addition, the detection speed of the dried blood spot sample can be accelerated by pre-loading the stable isotope internal standard in the sample carrier, the influence of some interference factors is eliminated, and the detection accuracy is higher.
The storage platform and the storage system provide storage positions for the quantitative absorption micro-sampling device, and are convenient for absorption and drying of blood samples in the quantitative absorption micro-sampling device and temporary storage, transfer and transportation of the quantitative absorption micro-sampling device.
Drawings
Fig. 1 is a schematic diagram of the overall structure of a quantitative absorption micro-sampling device according to an embodiment of the present invention.
FIG. 2 is an exploded view of a quantitative absorption micro-sampling device according to an embodiment of the present invention.
FIG. 3 is a cross-sectional view of a quantitative absorption micro-sampling device according to an embodiment of the present invention.
FIG. 4 is a top view of a quantitative absorption micro-sampling device according to a second embodiment of the present invention.
Fig. 5 is a sectional view in the direction D-D of fig. 4.
Fig. 6 is a partial enlarged view of fig. 5.
Fig. 7 is a schematic structural diagram of a storage platform according to a fourth embodiment of the present invention.
Reference numerals illustrate: 1. a cover body; 11. an upper cover; 12. a fixing slot; 13. an outer snap ring; 2. a case body; 21. a bottom box; 22. a perspective part; 221. an upper clamping ring; 222. perspective ring window; 223. a lower clamping ring; 3. quantifying a blood collection tube; 31. a first tube body; 32. a second tube body; 33. a connection part; 331. a fixed arm; 332. a communication port; 4. a sample carrier; 5. a bracket; 51. a support plate; 511. a flow hole; 52. a partition plate; 53. a support ring; 531. a placement groove; 532. placing a plate; 533. a through hole; 6. a drying bin; 7. a storage platform; 71. a platform body; 72. an accommodating groove.
Detailed Description
The following detailed description of the invention is provided in connection with specific embodiments and with the accompanying figures 1-7 to provide those skilled in the art with a more complete understanding of the objects, features and effects of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. To the extent that the definition of a term in this document conflicts with the meaning commonly understood by those skilled in the art to which this invention pertains, the definition set forth herein controls.
The invention improves the existing dry blood spot sampling technology by providing the quantitative absorption micro sampling device, the storage platform and the storage system, thereby preventing the situation that the detection cannot be carried out due to the damage of single dry blood spots.
Example 1
As a specific embodiment of the present invention, this embodiment provides a quantitative absorption micro-sampling device, referring to fig. 1 and 2, which includes a cover 1, a box 2, a plurality of quantitative blood collection tubes 3, and a sample carrier 4. The cover body 1 is matched with the box body 2, and when the cover body 1 is connected with the box body 2, a closed space is formed, so that the cover body is relatively separated from the external environment, an independent internal micro-environment is formed inside the quantitative absorption micro-sampling device, and the formation and storage environment of the dry blood spots are not polluted. The quantitative blood collection tubes 3 are fixed on the cover body 1 and extend towards the direction of the box body 2, the sample carriers 4 are located in the box body 2, the number of the sample carriers 4 is equal to that of the quantitative blood collection tubes 3, the quantitative blood collection tubes 3 are in one-to-one correspondence with the sample carriers 4, the bottom openings of the quantitative blood collection tubes 3 are in contact with the sample carriers 4, and the plurality of sample carriers 4 are not in contact. The sample carrier 4 is used for completely absorbing a specific volume of the blood sample sucked by the quantitative blood collection tube 3, so that the blood sample is transferred from the quantitative blood collection tube 3 to the sample carrier 4.
The quantitative blood collection tubes 3 are fixed on the cover body 1, so that the cover body 1 can be held by hands to transfer a plurality of quantitative blood collection tubes 3 at one time, and the sampling and transferring efficiency of the quantitative blood collection tubes 3 is improved. During sampling, the cover body 1 can be held by hand, different quantitative blood collection tubes 3 can be used for sucking blood samples in sequence, and finally, the sampling of all the quantitative blood collection tubes 3 is completed.
When the dry blood spot sample is collected, firstly, the cover body 1 is held by a hand and a plurality of quantitative blood collection tubes 3 are used for respectively sucking human blood samples, then the cover body 1 carrying the quantitative blood collection tubes 3 is covered on the box body 2, the bottom ends of the quantitative blood collection tubes 3 are contacted with the sample carrier 4, and the blood samples in the quantitative blood collection tubes 3 are completely absorbed by the sample carrier 4 and dried in the box body 2 to form the dry blood spot sample. Since the box body 2 is internally provided with a plurality of sample carriers 4 corresponding to the quantitative blood collection tube 3, a plurality of dried blood spot samples can be obtained. Part of the dried blood spot sample is used as a detection sample, and the rest of the dried blood spot sample is used as a backup sample. Since the dried blood spot samples are formed and stored in the same internal environment, consistency of a plurality of dried blood spots can be ensured.
When the detection sample is damaged due to unexpected situations and cannot be detected, the backup sample is started, and resampling is not needed. On the one hand, if resampling is performed, the newly collected blood sample and the originally collected blood sample will have differences due to the longer time interval, the detection results are inconsistent, and the real condition of the collected person at the original collection time cannot be accurately reflected; on the other hand, re-acquisition will increase the acquisition cost by a large amount, burdening the acquired person.
Specifically, the quantitative absorption microsampling device is in an elliptical cylinder shape as a whole. The horizontal sections of the cover body 1 and the box body 2 are elliptical sections. By adopting the oval design, the micro-sampling device is convenient for operators to hold, and the volume and the weight of the micro-sampling device can be reduced. The number of quantitative blood collection tubes 3 and sample carriers 4 was 2.
Referring to fig. 2 and 3, the cover 1 includes an upper cover 11, and a fixing slot 12 for installing the quantitative blood collection tubes 3 is formed in the bottom surface of the upper cover 11, and the number of the fixing slots 12 is equal to the number of the quantitative blood collection tubes 3. An outer clamping ring 13 clamped with the box body 2 is fixed at the outer edge of the bottom surface of the upper cover 11.
The quantitative blood collection tube 3 comprises a tube body and a connecting part 33, and the connecting part 33 is fixed at the top end of the tube body. The fixing clamping groove 12 forms a fixing structure of the connecting part 33, and the connecting part 33 is inserted into the fixing clamping groove 12 of the upper cover 11 and is clamped with the upper cover 11, so that the quantitative blood collection tube 3 is convenient to install, detach and replace.
In this embodiment, the connecting portion 33 is plate-shaped, and the shape of the fixing clip groove 12 matches the shape of the connecting portion 33 to ensure connection of the connecting portion 33 and the upper cover 11. A plurality of punctiform bulges are formed on the two side plate surfaces of the connecting part 33, so that the connecting part 33 is more firmly connected with the upper cover 11 after being inserted into the fixing clamping groove 12, and the quantitative blood collection tube 3 is prevented from falling off in the moving process.
The lower edge of the connecting portion 33 is integrally formed with fixing arms 331 extending downward and spaced apart from each other. The tube body of the quantitative blood collection tube 3 is positioned between the two fixed arms 331 and is fixedly connected with the fixed arms 331. A communication port 332 is formed by leaving a distance between the top end of the tube body and the connecting portion 33 so that the top end of the tube body is in an open state communicating with the outside.
In this embodiment, the tube body includes a first tube body 31 and a second tube body 32, wherein the first tube body 31 is a single quantitative capillary tube, the second tube body 32 is two quantitative capillary tubes, and two ends of the quantitative capillary tubes are open. A specified volume of blood sample can be accurately absorbed by the quantitative capillary. The capacity of a single quantitative capillary may be 15-60uL, preferably 50uL. The external specifications of the connection part 33 connected with the first tube body 31 and the second tube body 32 can be the same, so that quantitative blood collection tubes 3 with different capillary numbers can be replaced conveniently, and the practicability and applicability are improved.
When distal blood sampling such as fingertip blood and heel blood is performed, different types of quantitative blood collection tubes 3 can be selected for adaptation according to the required blood volume, so that sufficient absorption volume is ensured, for example, when a single capillary tube is insufficient for absorbing the required blood volume, the quantitative blood collection tubes 3 with the second tube bodies 32 with two capillaries can be replaced for blood sample collection. In this embodiment, one of the two quantitative blood collection tubes 3 is selected from the first tube 31, and the other tube is selected from the second tube 32.
The case 2 includes a bottom case 21 and a transparent see-through portion 22. The perspective part 22 is respectively clamped with the cover body 1 and the bottom box 21, and when in use, the perspective part 22 is respectively clamped with the cover body 1 and the bottom box 21 to form an integral structure. The perspective part 22 is ring-shaped with upper and lower openings, and comprises an upper clamping ring 221 clamped with the outer clamping ring 13 of the cover body 1, a lower clamping ring 223 clamped with the bottom box 21, and a perspective ring window 222 positioned between the upper clamping ring 221 and the lower clamping ring 223, wherein the upper clamping ring 221, the perspective ring window 222 and the lower clamping ring 223 are integrally formed. Specifically, after connection, the upper clamping ring 221 is located inside the outer clamping ring 13, and the lower clamping ring 223 is located inside the bottom case 21. The outer surface of the see-through ring window 222 is flush with the outer surfaces of the outer collar 13 and the bottom box 21.
The bottom box 21 has mounted therein a holder 5 for the sample carrier 4. The space in the bottom box 21 below the support 5 forms a drying compartment 6.
The desiccant in the drying chamber 6 is used to maintain a dry environment within the cartridge, to expedite the drying of the blood sample in the sample carrier 4, to reduce the time for dry blood spots to form, and to maintain a stable internal microenvironment.
Referring to fig. 1 and 3, the sample carrier 4 can be clearly observed through the see-through annular window 222 of the see-through portion 22, so that the condition of absorption and transfer of the blood sample and the condition of formation of the dried blood spots by the sample carrier 4 can be easily visually observed. Preferably, the tube body of the quantitative blood collection tube 3 is also made of transparent material, so that the remaining condition of blood transfer in the tube body can be observed through the perspective ring window 222, and whether the remaining condition is completely absorbed by the sample carrier 4 or not. The provision of the see-through annular window 222 may allow an operator to more easily grasp the formation process of the dried blood spot sample.
Specifically, the bracket 5 includes an oval support plate 51, support rings 53 disposed on the upper surface of the support plate 51 at intervals, and a spacer plate 52 for spacing the support rings 53, wherein the height of the spacer plate 52 is greater than that of the support rings 53. The bottom surface of the support plate 51 is provided with a flow hole 511 for communicating the support ring 53 with the drying chamber 6. Through the flow holes 511, air circulation is achieved, and drying of the blood sample is accelerated.
A placement table is provided at an upper portion of an inner surface of the bottom case 21 for placing the stay 51 and supporting the stay 51. The upper part of the inner surface of the support ring 53 is formed with an inwardly protruding support table for the placement of the sample carrier 4. The shape of the sample carrier 4 matches the shape of the support ring 53. In this embodiment, the sample carrier 4 is circular. The distance between the upper surface of the support table and the top end of the support ring 53 is equal to the thickness of the sample carrier 4, and when the sample carrier 4 is placed on the support table, the upper surface of the sample carrier 4 is flush with the top end of the support ring 53, so that the sample carrier 4 is completely positioned in the support ring 53, and the sample carrier 4 is prevented from being displaced while the sample carrier 4 is protected. The separation plate 52 separates the sample carriers 4 from each other and prevents the sample carriers 4 from affecting each other.
Preferably, the sample carrier 4 has a thickness of 1mm and the sample carrier 4 has a circular shape. In other embodiments, the thickness of the sample carrier 4 may be, but is not limited to, 0.8mm, 1.2mm, 1.5mm.
Further, a pressing plate protruding inwards is arranged on the inner surface of the perspective part 22, and after the perspective part 22 is clamped with the bottom box 21, the pressing plate presses the edge of the sample carrier 4 to fix and limit the sample carrier 4, so that the sample carrier 4 is prevented from moving randomly. The pressure plate simultaneously compresses the support ring 53, so that the support 5 is stabilized against movement in the case 2.
After the cover body 1 and the box body 2 are combined, the bottom end of the quantitative blood collection tube 3 is contacted with the upper surface of the sample carrier 4, the quantitative blood collection tubes 3 are in one-to-one correspondence with the sample carrier 4, and the bottom end of the quantitative blood collection tube 3 is positioned in the middle of the sample carrier 4, so that the sample carrier 4 can uniformly distribute the absorbed blood in the quantitative blood collection tubes 3 to form dry blood spots.
Preferably, the sample carrier 4 is medical filter paper, and in other embodiments, the sample carrier 4 may be a blood sucking plate made of other synthetic materials that are satisfactory.
The adoption of a plurality of quantitative blood collection tubes 3 for blood collection can also ensure enough blood collection amount, and is helpful for meeting the requirement of later detection on sample size. A plurality of dry blood spot samples formed by one-time blood sampling can be used for backing up the single detection project, can also provide support for other detection projects, and is beneficial to developing more detection projects.
When the quantitative absorption micro sampling device is assembled, firstly, the bracket 5 carrying the sample carrier 4 is placed on the bottom box 21 filled with the drying agent, then the perspective part 22 is clamped to the bottom box 21, the fixing of the sample carrier 4 and the limiting of the bracket 5 are formed, and finally, the cover body 1 carrying the quantitative blood collection tube 3 for collecting the blood sample is clamped to the perspective part 22. After the assembly is completed, the sample carrier 4 absorbs the blood sample in the quantitative blood collection tube 3, and a dry blood spot sample is obtained after drying.
When the later detection is needed, the sample carrier 4 with the dried blood spot sample is exposed after the bottom box 21 and the perspective part 22 are separated, the dried blood spot sample to be detected is transferred according to the need, and the residual dried blood spot sample can be continuously stored in the quantitative absorption sampling device for backup detection or detection of other items. In other embodiments, the rack 5 can be directly lifted to transfer all the dry blood spot samples together, so that the transfer efficiency of the dry blood spot samples is improved.
Because the humidity of storage and transportation and the folds of the dried blood spot sample carrier 4 can all influence the final detection result, in the embodiment, the sample carrier 4 is fixed on the basis of adopting a closed space and internally arranging a drying agent, the sample carrier 4 is not influenced by external environment, the sample carrier 4 is maintained in an initial form, and the folds of the sample carrier 4 in the storage and transportation processes are avoided, so that the stability of the dried blood spot sample is ensured.
The quantitative absorption microsampling device disclosed by the invention has the advantages that firstly, after the cover body 1 and the box body 2 are combined, a closed space isolated from the outside is formed, the dried blood spots are prevented from being exposed in the air in the forming, storing and transporting processes, and the influence of external factors is reduced, so that a plurality of dried blood spot samples are ensured to be formed in the same microenvironment; when the detection is performed in the later period, if the detection cannot be performed due to the fact that damage occurs in one part of the detection, other backup samples can be used for detection, so that the situation that the detection cannot be performed is avoided; meanwhile, as all the dry blood spot samples are formed and stored in the same environment, the consistency of the components and the properties of the dry blood spot samples can be ensured, and the detection results are not different due to the difference of the dry blood spot samples.
Therefore, the quantitative absorption microsampling device not only acquires a plurality of dry blood spot samples at one time, but also forms and stores all the dry blood spot samples synchronously in the same dry environment, and all the dry blood spot samples are affected by the microenvironment, so that the detection results of all the dry blood spot samples are consistent except instrument errors and operation errors in final detection.
In addition, on the premise that the detection sample is used for obtaining the detection result and meeting the ethical requirement, the backup sample can be used for detecting various projects so as to support medical research works, such as medical data mining and medical model training, and further promote the progress of medical clinical practice.
Example two
As a specific embodiment of the present invention, this embodiment provides a quantitative absorption micro-sampling device, referring to fig. 4 and 5, which is different from the first embodiment in that the quantitative blood sampling tube 3 has the same type of second tube 32. The amount of blood collected is increased by increasing the number of quantitative capillaries to increase the detectable sample content in the dried blood spot sample.
Referring to fig. 5 and 6, a horizontal placement plate 532 is fixed to an upper inner wall of the support ring 53, and the placement plate 532 partitions the support ring 53 up and down. The placement plate 532 and the portion of the support ring 53 above the placement plate 532 form a placement groove 531 for placing the sample carrier 4. The distance of the upper surface of the placing plate 532 from the top end of the support ring 53 is equal to the thickness of the sample carrier 4. When the sample carrier 4 is placed in the placement groove 531, the upper surface of the sample carrier 4 is flush with the top end of the support ring 53, thereby ensuring that the sample carrier 4 is completely located in the placement groove 531. The placement plate 532 is provided to provide a more effective and stable support for the sample carrier 4 than the support table in the first embodiment.
The placing plate 532 is provided with a plurality of through holes 533 penetrating through the upper plate surface and the lower plate surface, so that air circulation between the upper plate surface and the lower plate surface of the placing plate 532 is ensured, dry air from the drying bin 6 can reach the sample carrier 4 through the circulation holes 511 of the support plate 51 and the through holes 533 of the placing plate 532, and moisture in the sample carrier 4 is taken away and absorbed by a drying agent, thereby accelerating the formation of a dry blood spot sample, and simultaneously enabling the inside of the quantitative absorption microsampling device to gradually reach a dry state.
In other embodiments, the quantitative absorption micro-sampling device may be a cube or a cylinder as a whole, and the quantitative blood collection tube 3 and the sample carrier 4 may be 3 or 4 in number.
The quantitative absorption micro sampling device is correspondingly adjusted according to the requirement, the number of the fixing clamping grooves 12 of the upper cover 11 and the quantitative blood collection tubes 3 is increased, and the number of the supporting rings 53 is correspondingly increased on the support 5 to place the sample carrier 4. The plurality of sample carriers 4 are also isolated from each other. In the first and second embodiments, two dried blood spot samples may be formed finally, and in other embodiments, three or four dried blood spot samples may be obtained by increasing the number of quantitative blood collection tubes 3 and sample carriers 4. When two dry blood spot samples are obtained in the same microenvironment, one of the two dry blood spot samples is used as a detection sample, and the other one is used as a backup sample; when multiple dried blood spot samples are obtained in the same microenvironment, the test sample and the backup sample may be selected as desired.
In other embodiments, the connecting portion 33 of the quantitative blood collection tube 3 may have other shapes, such as a circle, a square, and the shape of the fixing clip groove 12 matches the shape of the connecting portion 33 so as to enable the connecting portion 33 to be inserted into the fixing clip groove 12 and stably clip with the upper cover 11.
In one embodiment, the connecting portion 33 of the quantitative blood collection tube 3 is circular and provided with external threads, the fixing clamping groove 12 is replaced by an internal threaded hole, and the connecting portion 33 is in threaded connection with the upper cover 11. The connection strength and the connection stability can be further improved by adopting a threaded connection mode.
In other embodiments, the type of the tube body of the quantitative blood collection tube 3 may be a type including three quantitative capillaries and other quantitative capillaries, in addition to the first tube body 31 including only a single quantitative capillary and the second tube body 32 including two quantitative capillaries in the first and second embodiments. The tube body adopts multitube design can satisfy the demand to blood sampling sample volume. In addition, the blood collection amount can be changed by changing the diameter of the quantitative capillary, namely, quantitative capillaries with different specifications are adopted.
Example III
As a specific embodiment of the present invention, this embodiment provides a quantitative absorption micro-sampling device. The sample carrier 4 in the quantitative absorption micro-sampling device adopts a modified sample carrier to improve the stability. The sample carrier 4 is modified by adding protective agents such as antioxidants, preservatives and/or enzyme inhibitors to the sample carrier 4. The sample carrier 4 in this example selects a filter paper.
Specifically, the types, ingredients and amounts of the protectants are shown in table 1. In this embodiment, only the type, name and concentration of part of the protecting agent is shown, and in other embodiments, other protecting agents may be used to modify the sample carrier 4, which is not shown here.
TABLE 1 protectant type, name, and concentration
Preparing a treatment liquid with a certain concentration by using a protective agent, soaking the sample carrier 4 in the treatment liquid for a certain time, taking out and drying to obtain the modified sample carrier 4.
Specifically, the modified sample carrier 4 is prepared by the following method:
1. selecting one or more protective agents in table 1, dissolving in 50% methanol water to obtain a treatment solution, wherein the concentration of each selected protective agent is shown in table 1;
2. Immersing the sample carrier 4 in the treatment liquid for 0.5-2 min, wherein the immersion time can be 0.5min, 1min, 1.5min or 2min;
3. And taking out the infiltrated sample carrier 4, and drying in a drying oven, wherein the drying temperature is 30-40 ℃, can be 30 ℃, 35 ℃ or 40 ℃, the drying time is 3-6 h, can be 3h, 4h, 5h or 6h, and the drying time is correspondingly shortened when the drying temperature is increased, so that the sample carrier 4 is completely dried, and the modified sample carrier 4 is obtained.
In order to verify the stability of the modified sample carrier, the following comparative experiments were designed.
First, a modified sample carrier was prepared by selecting 20ppm of merthiolate, 10mM of disodium edetate, 5mM of ascorbic acid, 30mM of sodium metabisulfite as a protective agent treatment solution, and at least 10 parts of the obtained modified sample carrier was obtained.
10 Anticoagulated blood samples are prepared and numbered 1-10, as well as 20 original sample carriers and 10 modified sample carriers. Transferring 20uL to a modified sample carrier and two original sample carriers under the same condition of the same anticoagulated blood sample, drying in the shade at room temperature overnight or not less than 5 hours, and transferring to a corresponding centrifuge tube for standby after all the collecting parts form dry blood spots.
Wherein, three samples obtained for the same anticoagulated blood sample, one of which is transferred to-80 ℃ environment, and the other is transferred to 40 ℃ environment, and after 14 days of preservation, the samples are used for stability improvement capability test. The above dried blood spot samples were extracted, tested and recorded under the same conditions, and the test results are shown in tables 2 and 3. Since stability is higher as the temperature is lower, it is considered that stability is lower as the temperature is higher, since the detection result of the sample stored at-80℃is used as a reference, and 40℃is used as the upper temperature limit at which the blood sample is naturally dried.
TABLE 2 modified Carrier sample and original Carrier sample comparison of sample detection results (tyrosine)
TABLE 3 modified Carrier sample and original Carrier sample comparison of sample detection results (acetylcarnitine)
As can be seen from tables 2 and 3, even when the sample is stored in an environment of 40 ℃ for 14 days, the concentration of the dried blood spot sample of the modified sample carrier is still relatively close to that of the dried blood spot sample stored in an environment of-80 ℃, the relative deviation is between 0.3% and 6.5% and 1.0% and 7.0%, while the concentration of the dried blood spot sample of the original sample carrier stored in an environment of 40 ℃ is greatly different from that of the dried blood spot sample stored in an environment of-80 ℃, and the relative deviation is between 12.6% and 24.4% and 26.7% and 44.5.
It can thus be obtained that the stability of the dried blood spot formed in the modified sample carrier is significantly higher than the stability of the dried blood spot formed in the original sample carrier.
In this embodiment, by modifying the sample carrier 4, the stability of the dried blood spot formed on the sample carrier 4 is improved, which is helpful for the formation and storage of the dried blood spot sample and the accuracy of the detection result.
Further, in order to facilitate quantitative detection of the dried blood spot sample, a stable isotope label (internal standard) is added to the sample carrier of the present embodiment. And in the later detection, the extracted stable isotope labeling substance is extracted together with the index to be detected and quantitatively analyzed by a mass spectrometry internal standard method.
The mass spectrometry isotope internal standard method (Isotope Dilution Mass Spectrometry, IDMS) is a technology commonly used for quantitative analysis and is widely applied in the fields of biochemistry, environmental science, drug research and development and the like. It uses an isotopic label as an internal standard, and the concentration of the target compound is determined by measurement of a mass spectrometer.
In mass spectrometry, an isotope standard of known concentration, which has the same chemical properties as the target compound but a different mass, is added to the sample to be measured, and an isotope of one or more neutral atoms heavier than the target compound is typically selected for labelling.
After the isotope standard is added, the target compound and the isotope standard in the sample are mixed in a certain proportion to form an internal standard compound with known concentration. The peak areas or peak heights of the target compound and the isotope standard were measured by analysis with a mass spectrometer. The concentration of the target compound in the sample can be calculated according to the proportional relationship between the two.
The mass spectrum isotope internal standard method has the advantages of eliminating a plurality of interference factors and improving the accuracy and reliability of analysis results. Because isotope standards have the same chemical properties as the target compounds, they are subjected to the same effects during sample processing, extraction and separation. Therefore, any factors affecting the target compound and the isotope standard can be effectively corrected, thereby improving the accuracy of the quantitative result.
Specifically, in this embodiment, the original sample carrier is processed to obtain a sample carrier containing an internal standard by the following method:
1. Preparing an internal standard treatment fluid: mixing 80ml of methanol and 20ml of water to form a diluent which contains 20mg of BHT (2, 6-di-tert-butyl-p-cresol); weighing and diluting to dissolve an internal standard to obtain a stock solution with a certain concentration, such as 1mg/ml; mixing the stock solution and the diluent according to a certain proportion to obtain an internal standard treatment solution, wherein the concentration of the final internal standard is 50+/-10 ng/mL;
2. 20uL of internal standard treatment solution was added to the original sample carrier and dried overnight in the shade to give a sample carrier containing the internal standard.
In detection, 200 μl of methanol was added to the dried blood spot sample containing the internal standard, ultrasound was performed at room temperature for 30min hours, the extract was transferred to a new 96-well deep hole sample plate, nitrogen was blown and concentrated to dryness, 50 μl of PTAD solution was added for derivatization 1 h, 20 μl of absolute ethanol was added, standing for 10min, the reaction liquid nitrogen was blown and concentrated to dryness, and 100 μl of 50% (V/V) methanol solution was re-dissolved and transferred to a 96-well cone bottom sample plate for LC-MS/MS analysis. Calibration is required before the instrument is detected.
The same blood samples were measured by the internal standard method and the conventional peripheral blood method, respectively, for 20 cases, and the comparison results are shown in Table 4.
Table 4 internal standard method and conventional peripheral blood method for comparing the results of measuring dried blood spot samples
Wherein, VD2 and VD3 are respectively an internal standard 25 hydroxy vitamin D2 and 25 hydroxy vitamin D3, the method 1 is an internal standard method, the method 2 is a conventional peripheral blood method, and the unit is ng/mL.
As can be seen from Table 4, the relative deviation of the measurement results of the two methods is not more than 20%, and is between 0 and 15.9% and between 0.4 and 15.9%.
Further, in order to verify the stability of the internal standard of the sample carrier, the following method was used for the test.
1. Preparing 20 parts of sample carriers treated by using an internal standard treatment liquid, and respectively placing 10 parts of the sample carriers in a refrigerator at-80 ℃ and an environment at 40 ℃ for 14 days;
2. Preparing 10 anticoagulated blood samples, numbering 1-10, and respectively transferring the 10 anticoagulated blood samples into sample carriers at two or more temperatures under the same conditions of the same anticoagulated blood sample;
3. the concentration was measured using an internal standard method and the relative deviation of the measured values under both environmental conditions was evaluated, after drying overnight or not less than 5 hours in the shade at room temperature.
The test results are shown in Table 5.
Table 5 comparison of stability results for internal Standard sample-containing Carrier
Wherein, VD2 and VD3 are respectively internal standard 25 hydroxy vitamin D2 and 25 hydroxy vitamin D3, and the unit is ng/mL. The relative deviation between the concentration obtained by the internal standard method in the internal standard sample carrier stored for 14 days in the environment of 40 ℃ below zero and the concentration obtained by the internal standard sample carrier stored for 14 days in the environment of-80 ℃ below zero is not more than 20 percent and is between 0.8 and 13.6 percent and 0 and 14.6 percent.
It can be seen from this that the internal standard in the sample carrier 4 has a relatively high stability and can be used for quantitative detection of the index to be detected by the internal standard method.
Example IV
As a specific embodiment of the present invention, referring to fig. 7, the storage platform 7 includes a platform body 71, and an accommodating groove 72 is formed on the upper surface of the platform body 71, where the accommodating groove 72 is used for accommodating the quantitative absorption micro sampling device in the first embodiment. The receiving slots 72 are preferably plural to facilitate storage of plural quantitative absorption microsampling devices at a time.
Specifically, referring to fig. 7, the platform body 71 in the present embodiment is square, which is convenient for processing and fixing. The accommodating groove 72 is a shape matching the shape of the quantitative absorption micro sampling device, and when the quantitative absorption micro sampling device is vertically placed in the accommodating groove 72, the quantitative absorption micro sampling device can be stabilized in the accommodating groove 72. The height of the quantitative absorption micro-sampling device is greater than the depth of the accommodating groove 72 so as to facilitate the taking out of the quantitative absorption micro-sampling device from the accommodating groove 72.
Preferably, the receiving groove 72 is a waist-shaped groove so as to be better compatible with the quantitative absorption micro-sampling device. The receiving grooves 72 are arranged in a plurality of rows, and the angle between the symmetry axis of the receiving grooves 72 and the side of the platform body 71 is 30-60 °, preferably 45 °.
Further, in order to enable the accommodating groove 72 to be perfectly matched with the elliptical cylindrical quantitative absorption micro-sampling device in the first embodiment, the shape of the accommodating groove 72 may be set to a corresponding elliptical shape to increase the stability of the quantitative absorption sampling device.
In other embodiments, the platform body 71 may have other shapes, such as a circle, and the angle between the symmetry axis of the receiving groove 72 and the side of the platform body is not limited. The shape of the receiving groove 72 is determined according to the shape of the quantitative absorption micro-sampling device. The shape of the accommodation groove 72 may or may not be identical to the shape of the quantitative absorption micro-sampling device, as long as the quantitative absorption micro-sampling device can be stabilized on the platform body 71.
The storage platform can provide a storage position for the quantitative absorption micro-sampling device, and is convenient for absorption and drying of blood samples in the quantitative absorption micro-sampling device and temporary storage, transfer and transportation of the quantitative absorption micro-sampling device.
After absorbing a trace amount of blood sample by the quantitative blood sampling tube 3, the cover body 1 is covered on the box body 2, and then the quantitative absorption trace amount sampling device is stored in the accommodating groove 72, so that the sample carrier 4 fully absorbs the blood sample in the capillary tube, and the drying of the blood sample is completed in the quantitative absorption trace amount sampling device, so that a dry blood spot sample is formed.
By providing the storage platform 7 matched with the quantitative absorption microsampling device, a plurality of quantitative absorption microsampling devices can be stored at the same time, and the storage and the transfer of the batch quantitative absorption microsampling devices are convenient.
Example five
As a specific embodiment of the present invention, the present invention provides a storage system, which includes a storage platform 7 and a quantitative absorption micro sampling device. The storage platform 7 is used for vertically storing the quantitative absorption micro-sampling device, specifically, the storage platform is the storage platform 7 in the second embodiment, and the quantitative absorption micro-sampling device is the quantitative absorption micro-sampling device in the first to third embodiments. By combining the storage platform 7 and the quantitative absorption microsampling device into a storage system, the dried blood spot is sampled more reliably, the stable absorption and drying of the blood sample are facilitated, and the transfer and transportation are more convenient.
The above description is only of the preferred embodiment of the present invention, and is not intended to limit the present invention in any other way, but is intended to cover any modifications or equivalent variations according to the technical spirit of the present invention, which fall within the scope of the present invention as defined by the appended claims.
Claims (7)
1. The quantitative absorption microsampling device comprises a cover body (1) and a box body (2), wherein the cover body (1) is matched with the box body (2) and connected to form a closed space to isolate an external environment, and the quantitative absorption microsampling device is characterized in that a plurality of quantitative blood collection tubes (3) which extend towards the box body (2) and are used for quantitatively collecting microsamples are fixed at the bottom of the cover body (1), sample carriers (4) which are equal in number and opposite to the quantitative blood collection tubes (3) and can absorb the blood samples one by one are fixed in the box body (2), the bottom ends of the quantitative blood collection tubes (3) are in contact with the sample carriers (4), and the sample carriers (4) absorb the quantitative blood samples in the quantitative blood collection tubes (3) and are dried in the same environment in the box body (2) to form a plurality of dried blood spots including detection samples and backup samples;
the box body (2) comprises a bottom box (21) and a perspective part (22) for observing the formation of a dried blood spot sample, the perspective part (22) comprises an upper clamping ring (221), a lower clamping ring (223) and a perspective ring window (222) positioned between the upper clamping ring (221) and the lower clamping ring (223), the upper clamping ring (221) is detachably connected with the cover body (1), and the lower clamping ring (223) is detachably connected with the bottom box (21);
the sample carrier (4) is placed on a bracket (5) which is positioned in the bottom box (21) and is close to a perspective ring window (222) of the perspective part (22), and the perspective part (22) is connected with the bottom box (21) to respectively fix the bracket (5) and the sample carrier (4) so as to limit the positions of the bracket (5) and the sample carrier (4);
The cover body (1) comprises an upper cover (11) and an outer clamping ring (13) which is detachably connected with an upper clamping ring (221) of the perspective part (22), and the quantitative blood collection tube (3) is fixed at the bottom of the upper cover (11);
a plurality of fixing clamping grooves (12) are formed in the bottom of the upper cover (11), the quantitative blood collection tube (3) comprises a tube body and a connecting portion (33), and the connecting portion (33) is inserted into the fixing clamping grooves (12) to be clamped with the upper cover (11);
The support (5) comprises a support plate (51) arranged on a placing table on the inner surface of the bottom box (21) and support rings (53) which are arranged on the upper surface of the support plate (51) at intervals and correspond to the quantitative blood collection tube (3), the sample carrier (4) is placed on the support rings (53), a protruding pressing plate is arranged on the inner surface of the perspective part (22), and the pressing plate respectively presses the edges of the sample carrier (4) and the support rings (53) to limit the movement of the sample carrier (4) and the support (5).
2. The quantitative absorption microsampling device according to claim 1, characterized in that the sample carrier (4) is a modified sample carrier with improved stability prepared by the following method:
dissolving at least one protective agent in methanol water to obtain a treatment liquid;
Step two, soaking an original sample carrier in the treatment liquid for 0.5-2 min;
and thirdly, taking out the infiltrated sample carrier, and drying the sample carrier in a drying oven, wherein the drying temperature is 30-40 ℃ and the drying time is 3-6 hours, so that the sample carrier is completely dried.
3. The quantitative absorption microsampling device according to claim 1, characterized in that the sample carrier (4) is a sample carrier containing stable isotope internal standard for improving the accuracy and reliability of the detection result of a dried blood spot sample, which is obtained by the following method:
firstly, mixing methanol and water in a certain proportion to obtain a diluent; diluting and dissolving an internal standard to obtain stock solution; mixing the stock solution and the diluent according to a certain proportion to obtain an internal standard treatment solution meeting the concentration requirement;
And step two, adding an internal standard treatment liquid to the original sample carrier and drying.
4. Quantitative absorption microsampling device according to claim 1, characterized in that the upper surface of the support plate (51) is provided with a spacer plate (52) separating the spaced support rings (53), the height of the spacer plate (52) being greater than the height of the support rings (53).
5. Quantitative absorption microsampling device according to any of the claims 1-4, characterized in that the cartridge (2) comprises a drying compartment (6) under the rack (5) filled with a drying agent, the drying compartment (6) being in communication with the space in which the sample carrier (4) is located.
6. A storage platform for storing the quantitative absorption micro-sampling device according to any one of claims 1 to 5, comprising a platform body (71), wherein at least one accommodation groove (72) is provided on the upper surface of the platform body (71), and the accommodation groove (72) accommodates the quantitative absorption micro-sampling device and stabilizes the quantitative absorption micro-sampling device.
7. A storage system comprising a quantitative absorption microsampling device according to any of claims 1-5 and a storage platform (7) according to claim 6, the quantitative absorption microsampling device being placed in a receiving groove (72) of the storage platform (7).
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