Blood index analysis device

Abstract

The invention provides a blood index analysis device, and relates to the technical field of biochemical analysis equipment, a first end of a collection channel is hermetically connected with a hollow microneedle, and the collection channel is communicated with the outside through the hollow microneedle; the microfluidic channels are communicated with the acquisition channels and the corresponding detection channels; the first end of the detection channel is connected with the negative pressure element, and the second end of the detection channel corresponds to the sampling area of the detection chip; a first valve core is arranged on the acquisition channel and is positioned between the hollow microneedle and the microfluidic channel; the detection channel is provided with an air channel communicated with the outside, and the air channel is provided with a second valve element. According to the blood index analysis device, integrated collection and detection of blood samples can be achieved, the overall structure is miniaturized, operation is easy, and the blood index analysis device can be applied to daily rapid blood detection and portable field measurement.

Description

Technical Field

[0001] The present application relates to the technical field of biochemical analysis equipment, and in particular to a blood index analysis device. Background Art

[0002] In fields such as clinical medicine and health management, blood biochemical analysis can help medical professionals and researchers more accurately assess a patient's physiological health status. Currently, blood biochemical analysis relies primarily on large instruments. These instruments are bulky, complex, and require specialized operator expertise, making them unsuitable for routine rapid testing or portable, on-site measurements. Summary of the Invention

[0003] In view of this, the present application provides a blood index analysis device, which aims to solve the problems that current blood biochemical analysis equipment is difficult to apply to daily rapid testing and portable on-site measurement.

[0004] In a first aspect, the present application provides a blood index analysis device, comprising: a hollow microneedle, a collection channel, a microfluidic channel, a detection channel, a negative pressure element, and a detection chip;

[0005] The first end of the collection channel is sealedly connected to the hollow microneedle, and the collection channel is connected to the outside through the hollow microneedle; the microfluidic channel connects the collection channel and the corresponding detection channel; the first end of the detection channel is connected to the negative pressure element, and the second end of the detection channel corresponds to the sampling area of the detection chip;

[0006] The collection channel is provided with a first valve core, which is located between the hollow microneedle and the microfluidic channel; the detection channel is provided with an air channel connected to the outside world, and the air channel is provided with a second valve core.

[0007] Optionally, the detection channel includes a storage area and a detection area that are connected, and the storage area is located above the detection area;

[0008] The microfluidic channel is connected to the storage area, a blood filter membrane is provided between the storage area and the detection area, and the air channel is connected to the detection area. Thus, the blood filter membrane facilitates filtering interfering substances, reducing the problem of low detection accuracy caused by the lack of blood filtration function in conventional detection devices.

[0009] Optionally, one collection channel is connected to multiple microfluidic channels;

[0010] Each microfluidic channel is connected to a detection channel;

[0011] Each detection channel corresponds to a detection chip.

[0012] Optionally, the collection channel is a through hole that sequentially passes through the microfluidic channel plate, the blood filter layer plate and the detection base plate, and the microfluidic channel plate, the blood filter layer plate and the detection base plate are vertically stacked and fixedly connected;

[0013] The detection channel is a through hole that sequentially passes through the microfluidic channel plate and the blood filter layer plate, and the detection base plate is provided with a mounting position for the detection chip corresponding to the second end of the detection channel.

[0014] Optionally, the microfluidic channel plate is connected to the negative pressure element via a membrane plate;

[0015] The film-covering plate is provided with a first through hole communicating with the detection channel and the negative pressure cavity of the negative pressure element.

[0016] Optionally, the negative pressure element includes a stacked first pressure plate, a negative pressure film, and a second pressure plate, and the negative pressure film is a self-recovering flexible material;

[0017] The first pressing plate and the second pressing plate cooperate to fix and clamp the negative pressure membrane;

[0018] The middle part of the negative pressure membrane bulges toward the first pressure plate to form a bulge, and a negative pressure cavity is formed inside the bulge. The first pressure plate opens a first gap corresponding to the bulge, and the second pressure plate opens a second gap corresponding to the negative pressure cavity.

[0019] Optionally, the microfluidic channel plate is provided with a U-shaped groove on a surface close to the membrane-covered plate, and two ends of the U-shaped groove are respectively connected to the collection channel and the corresponding detection channel;

[0020] The film-covering plate is sealed and pressed on one side of the opening of the U-shaped groove, and the film-covering plate cooperates with the U-shaped groove to form the microfluidic channel.

[0021] Optionally, the detection chip is a three-electrode sensor chip, and the working electrodes of the detection chip are pre-coated with an enzyme solution;

[0022] The second end of the detection channel corresponds to the working electrode, reference electrode and counter electrode of the detection chip. The shape of the working electrode corresponds to the port shape of the second end of the detection channel. The reference electrode and counter electrode are arranged around the working electrode, and the reference electrode corresponds to the shape of the working electrode.

[0023] Optionally, the enzyme solution is a glucose oxidase solution or a lactate oxidase solution,

[0024] The glucose oxidase solution and the lactate oxidase solution both use hydroxymethylferrocene as a medium and use bovine serum albumin and glutaraldehyde as cross-linking agents.

[0025] Optionally, a first annular groove is provided around the first port of the collection channel on the blood filter layer plate, and a second annular groove 712 is provided around the second port of the collection channel on the blood filter layer plate, wherein the first port and the second port are respectively located on two opposite surfaces of the blood filter layer plate;

[0026] A third annular groove is provided around the third port of the detection channel on the blood filter layer plate, and a fourth annular groove is provided around the fourth port of the collection channel on the blood filter layer plate, wherein the third port and the fourth port are respectively located on two opposite surfaces of the blood filter layer plate;

[0027] The first ring groove, the second ring groove, the third ring groove and the fourth ring groove are all provided with a sealing rubber ring, and the thickness of the sealing rubber ring is higher than the depth of the ring groove;

[0028] The third port is covered with a blood filter membrane, the outer periphery of which is pressed against the inner side wall of the third annular groove by a sealing rubber ring corresponding to the third annular groove. The third port is an opening of the blood filter layer plate on a side surface close to the microfluidic channel plate.

[0029] The sealing rubber ring of the fourth annular groove surrounds the working electrode, reference electrode and counter electrode on the corresponding detection chip.

[0030] The present application provides a blood index analysis device, comprising a hollow microneedle, a collection channel, a microfluidic channel, a detection channel, a negative pressure element, and a detection chip; the first end of the collection channel is sealedly connected to the hollow microneedle, and the collection channel is connected to the outside through the hollow microneedle; the microfluidic channel connects the collection channel and the corresponding detection channel; the first end of the detection channel is connected to the negative pressure element, and the second end of the detection channel corresponds to the sampling area of the detection chip; the collection channel is provided with a first valve core, the first valve core is located between the hollow microneedle and the microfluidic channel; the detection channel is provided with an air channel connected to the outside, and the air channel is provided with a second valve core. In this way, the negative pressure element provides a driving force for collecting and transmitting blood samples, blood is collected through the hollow microneedle and the collection channel, the blood sample is transmitted to the detection channel through the microfluidic channel, and the detection channel cooperates with the corresponding detection chip to complete the detection of the blood sample, thereby realizing integrated blood collection and detection. The overall structure of the device is miniaturized, which is conducive to daily rapid detection and portable measurement. At the same time, the detection channel can be provided with a blood filter membrane, which is beneficial for filtering interfering substances in the blood and improving the accuracy of the detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in this embodiment or the prior art, the following briefly introduces the drawings required for use in the embodiment or the prior art description. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0032] Figure 1 A schematic diagram of the structure of a blood index analysis device provided in an embodiment of the present application;

[0033] Figure 2 A schematic structural diagram of a first pressing plate provided in an embodiment of the present application;

[0034] Figure 3 A schematic structural diagram of a negative pressure membrane provided in an embodiment of the present application;

[0035] Figure 4 A schematic structural diagram of a second pressing plate provided in an embodiment of the present application;

[0036] Figure 5 A schematic structural diagram of a film-coated board provided in an embodiment of the present application;

[0037] Figure 6 A schematic structural diagram of a microfluidic channel plate provided in an embodiment of the present application;

[0038] Figure 7 A schematic structural diagram of a blood filter layer provided in an embodiment of the present application;

[0039] Figure 8 A schematic structural diagram of a detection base plate provided in an embodiment of the present application;

[0040] Figure 9 A schematic diagram of the structure of a detection chip provided in an embodiment of the present application;

[0041] Figure 10 A schematic diagram of the combined structure of a blood index analysis device provided in an embodiment of the present application;

[0042] Figure 11 An exploded view of the left side of a blood index analysis device provided in an embodiment of the present application;

[0043] Figure 12 A schematic diagram of a blood marker analysis device provided in an embodiment of the present application.

[0044] Description of the accompanying figures

[0045] 1-detection chip; 11-working electrode; 12-reference electrode; 13-counter electrode;

[0046] 2-first pressing plate; 21-first clearance; 22-29-screw countersunk holes for the first pressing plate;

[0047] 3-negative pressure membrane; 31-raised portion; 32-39-screw holes for the negative pressure membrane;

[0048] 4 - second pressing plate; 41 - second clearance; 42-49 - screw holes for the second pressing plate;

[0049] 5-film-covered board; 51-58-screw holes of the film-covered board; 59-first via hole;

[0050] 6 - microfluidic channel plate; 60 - collection subchannel 1; 61-64, 66, 68 - screw holes of the microfluidic channel plate; 65, 67 - screw bottom holes of the microfluidic channel plate; 69 - microfluidic channel; 610 - detection subchannel 1;

[0051] 7 - Blood filter plate; 70 - Collection subchannel 2; 71-74, 76, 78 - Screw holes for the blood filter plate; 75 - First valve core slot; 77 - Second valve core slot; 79 - Air channel; 710 - Detection subchannel 2; 711 - First annular groove; 712 - Second annular groove; 713 - Third annular groove; 714 - Fourth annular groove; 715 - Blood filter membrane; a-d - Sealing rubber rings;

[0052] 8 - detection base plate; 80 - acquisition sub-channel three; 81-84, 86, 88 - detection base plate screw holes; 85 - mounting position; 87 - AB glue;

[0053] 9-Hollow microneedles. DETAILED DESCRIPTION

[0054] In the fields of clinical medicine and health management, blood biochemical analysis technology can analyze a variety of blood indicators (such as blood sugar, etc.) of the subjects, helping medical staff and researchers to more accurately grasp the physiological health status of the subjects. Common blood analysis methods include spectrophotometry, enzyme-linked immunosorbent assay, fluorescence detection, etc., which require large laboratory equipment such as spectrophotometers, microplate readers and high-performance liquid chromatographs. Because such instruments are often large in size and have complex operating procedures, they are highly dependent on laboratory environments and professionals. At the same time, these instruments usually have high requirements for sample volume or consumables. Not only are they expensive to use, but they are also difficult to meet the needs of daily rapid monitoring and portability.

[0055] Furthermore, when obtaining the blood of the subject, the traditional method is to use venous blood collection or fingertip blood collection. Among them, for venous blood collection, a large volume of blood samples is often collected through vacuum blood collection tubes or syringes, which not only has high requirements for the operating environment and personnel professionalism, but also easily causes tension or pain in patients; when multiple indicators need to be tested, in order to meet the needs of different test items, multiple blood collection tubes are often required, which further increases the tediousness of blood collection and the amount of blood sample collected. For fingertip blood collection, although the amount of blood collected can be reduced, it is also easy to cause pain and discomfort due to the dense nerves in the finger area. Of course, in recent years, non-invasive detection methods have also emerged, which have the advantage of high comfort, such as the detection of blood sugar, blood samples and heart rate through optical detection technology, but such detection methods are only applicable to a small number of physiological indicators. It is still difficult to test more complex or delicate blood parameters, and there is still controversy in terms of accuracy and precision.

[0056] Based on the above problems, the present application provides a blood index analysis device, which provides a driving force for collecting and transmitting blood samples through a negative pressure element, collects blood through a hollow microneedle and a collection channel, transmits blood samples through a microfluidic channel, and detects blood samples through a detection channel in conjunction with a corresponding detection chip, completing the collection and detection of blood samples in an integrated manner without relying on large-scale detection equipment. The overall structure is miniaturized, which is conducive to daily rapid detection and portable measurement. In addition, electrochemical analysis is performed using a detection chip to achieve accurate detection with less blood samples. At the same time, the hollow microneedle is used to reduce the pain of the test subject. The entire device can achieve one-time blood collection, and multiple detection channels and detection chips with different indicators configured for multiple detection channels are used to achieve multiple indicator analysis, reducing steps such as quantitative sampling and improving the convenience of operation.

[0057] In order to be able to understand the features and technical content of the embodiments of the present disclosure in more detail, the implementation of the embodiments of the present disclosure is described in detail below in conjunction with the accompanying drawings. The accompanying drawings are for reference only and are not used to limit the embodiments of the present disclosure. In the following technical description, for the sake of convenience of explanation, a full understanding of the disclosed embodiments is provided through multiple details. However, one or more embodiments can still be implemented without these details. In other cases, to simplify the drawings, well-known structures and devices can be simplified for display.

[0058] In the description and claims of the embodiments of the present disclosure, as well as in the accompanying drawings, the terms "first," "second," and the like are used to distinguish similar items and are not necessarily used to describe a particular order or precedence. It should be understood that the terms used in this manner are interchangeable where appropriate to describe the embodiments of the present disclosure herein. In addition, the terms "including," "having," and any variations thereof are intended to cover non-exclusive inclusions.

[0059] Unless otherwise stated, the term "plurality" means two or more.

[0060] In the embodiment of the present disclosure, the character " / " indicates that the preceding and following objects are in an "or" relationship. For example, A / B means: A or B.

[0061] The term "and / or" describes an association between objects, indicating that three relationships can exist. For example, A and / or B means: A or B, or A and B.

[0062] In order to make the purpose, technical solutions and advantages of the embodiments of this application more clear, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0063] See also Figure 1 , Figure 1 This is a structural schematic diagram of a blood index analysis device provided in an embodiment of the present application. A blood index analysis device includes: a hollow microneedle, a collection channel, a microfluidic channel, a detection channel, a negative pressure element and a detection chip.

[0064] The first end of the collection channel is sealed and connected to the hollow microneedle, and the collection channel is connected to the outside through the hollow microneedle; the microfluidic channel connects the collection channel and the corresponding detection channel; the first end of the detection channel is connected to the negative pressure element, and the second end of the detection channel corresponds to the sampling area of the detection chip.

[0065] The first end (input end) of the above-mentioned collection channel can be sealed and connected to the outer wall of the hollow microneedle. Optionally, the sealed connection can be achieved by means of sealant (such as AB glue), and blood can be collected and input through the hollow microneedle. When collecting blood and other materials through the hollow microneedle, the microneedle structure generally has a micron-level size, which can efficiently penetrate the stratum corneum of the skin in a short time, and the amount of bleeding after puncture is limited, which can effectively reduce the physiological stimulation to the subject, and can reduce the pain of traditional blood drawing, and can more accurately obtain a clean and stable blood sample.

[0066] The microfluidic channel can connect the second end of the collection channel and the first end of the detection channel. This allows the collection channel and the detection channel to be connected via the microfluidic channel, allowing the test liquid collected by the collection channel to be transferred to the detection channel for analysis by the detection chip at the second end of the detection channel. Microfluidic channels are tiny fluid channel structures designed and manufactured at the micrometer scale (typically ranging from tens to hundreds of micrometers) for manipulating and processing trace amounts of liquid (nanoliter to microliter). They are the core components of microfluidic chips or microfluidic systems and are widely used in fields such as biomedical analysis, chemical synthesis, and environmental monitoring.

[0067] The above-mentioned collection channel is equipped with a first valve core, which is arranged between the hollow microneedle and the microfluidic channel. The first valve core is used to control the conductivity of the collection channel; the detection channel is provided with an air channel connected to the outside world, and the air channel is equipped with a second valve core, which is used to control the conductivity of the air channel.

[0068] Optionally, the first end of the detection channel is located above the second end of the detection channel, which is beneficial for the blood transmitted from the microfluidic channel to enter the detection channel and fall onto the detection chip below.

[0069] Optionally, the detection channel is arranged vertically, and the air channel is arranged horizontally.

[0070] The valve core is used to control the conductivity of the collection channel, and the second valve core is used to control the conductivity of the air channel. In this way, the negative pressure element connected to the first end of the detection channel can first control the air channel to be non-conductive through the second valve core, and control the collection channel to be conductive through the first valve core, and discharge the gas from the microfluidic channel and the collection channel through the negative pressure element and the hollow microneedle. Then, the hollow microneedle is inserted into the position for collecting blood, and the liquid to be tested is collected based on the negative pressure formed by the negative pressure element. After the collection is completed, the collection channel is non-conductive by controlling the first valve core, and the second valve core and the negative pressure element are controlled to assist in causing the blood previously collected in the detection channel to fall onto the detection chip, so as to realize the analysis of the liquid to be tested.

[0071] Based on the above-mentioned device, the present application provides the driving force for collection and transmission through a negative pressure element, realizes blood collection through a hollow microneedle and a collection channel, transmits blood samples through a microfluidic channel, and completes detection through a detection channel in conjunction with a corresponding detection chip. In this way, the collection and detection of blood samples are completed in an integrated manner, and the overall structure is miniaturized, which is conducive to daily rapid detection and portable measurement.

[0072] Based on the above device, in a possible implementation, the above detection channel may include a storage area and a detection area that are connected, and the storage area is located above the detection area;

[0073] The microfluidic channel is connected to the storage area, a blood filter membrane is provided between the storage area and the detection area, and the air channel is connected to the detection area.

[0074] The blood filter membrane that can be set between the above-mentioned storage area and the detection area is intended to remove red blood cells, white blood cells, platelets and other potential interfering substances in the blood by physical or chemical methods, so as to improve the accuracy and reliability of subsequent electrochemical detection of blood indicators (such as glucose, lactate, electrolytes, etc.).

[0075] Optionally, the air channel is opened in the detection zone of the detection channel. Once the air channel is opened, the air pressure in the detection channel is kept consistent with the external air pressure, which facilitates the downward movement of blood in the detection channel by the negative pressure element after collection. Furthermore, the storage area can be used to store a portion of the blood collected by the hollow microneedle, so that the negative pressure element can subsequently push the blood through the blood filter membrane and into the detection zone.

[0076] Based on the above device, in a possible implementation, multiple microfluidic channels can be provided. Therefore, one collection channel can be connected to multiple microfluidic channels; each microfluidic channel is connected to a detection channel; and each detection channel corresponds to a detection chip.

[0077] The blood sampled through a collection channel is then transported to the detection channels corresponding to each microfluidic channel through multiple microfluidic channels. The blood transported by the detection channel is detected by the detection chip corresponding to each detection channel. In this way, different detection channels are equipped with different detection chips to achieve one blood collection and multi-index detection without interfering with each other.

[0078] Optionally, the number of microfluidic channels of the device is configured based on the number of indicators that need to be detected, and then a detection channel and a detection chip are configured for each microfluidic channel.

[0079] The following describes a structural embodiment of a blood index analysis device by taking the example of two detection indicators, that is, configuring two microfluidic channels for the collection channel, and configuring one detection channel and one detection chip for each corresponding microfluidic channel.

[0080] See also Figure 6 A schematic diagram of the structure of a microfluidic channel plate shown in FIG. Figure 7 The structural diagram of a blood filter layer shown in FIG. Figure 8 The above-mentioned collection channel and detection channel can be set based on the fixed stacked microfluidic channel plate, blood filter layer plate and detection base plate, which can be:

[0081] In one example, the collection channel is a through hole that sequentially passes through the microfluidic channel plate, the blood filter layer plate and the detection base plate, and the microfluidic channel plate, the blood filter layer plate and the detection base plate are vertically stacked and fixedly connected.

[0082] Understandably, see Figures 6-8 The collection channels form collection subchannel 1 60 on the microfluidic channel plate, collection subchannel 2 70 on the blood filter layer plate, and collection subchannel 3 80 on the detection base plate. The collection subchannels 1 60, 2 70, and 3 80 can extend vertically through the microfluidic channel plate.

[0083] In one example, the detection channel is a through hole that sequentially passes through the microfluidic channel plate and the blood filter layer plate, and the detection base plate is provided with a mounting position 85 for the detection chip 1 corresponding to the second end of the detection channel.

[0084] Understandably, see Figures 6-8 The above-mentioned detection channel forms a detection sub-channel 1 610 on the microfluidic channel plate and forms a detection sub-channel 2 710 on the blood filter layer plate. The above-mentioned detection sub-channel 1 610 and the detection sub-channel 2 710 can be vertically connected perpendicular to the above-mentioned microfluidic channel plate.

[0085] Optionally, taking the above-mentioned collection channel corresponding to two microfluidic channels 69 as an example, the microfluidic channel plate and the blood filter layer plate combination in the device is configured with two detection channels; each detection channel corresponds to a mounting position 85 of a detection chip 1.

[0086] Optionally, the mounting position 85 of the detection chip 1 on the detection base plate can cooperate with the blood filter layer plate to form a slot with an opening on one side of the detection base plate. After the device is assembled, the corresponding detection chip 1 can be inserted into the mounting position 85 to test the corresponding indicator of the detection chip 1, thereby facilitating the installation of the detection chip 1. After the detection chip 1 is installed in place, the second end of the detection channel is disconnected from the outside of the device. During testing, the working electrode, reference electrode, and counter electrode of the detection chip 1 need to be covered by the blood sample.

[0087] Optionally, the vertical stack of the microfluidic channel plate, blood filter layer plate, and detection base plate can be secured by arranging multiple screws. The material used can be PMMA (Polymethylmethacrylate), a transparent thermoplastic commonly known as organic glass or acrylic, which features high transparency, high strength, and ease of processing. Optionally, the thicknesses of the microfluidic channel plate, blood filter layer plate, and detection base plate can be 4 mm, 6 mm, and 3 mm, respectively.

[0088] Optionally, the microfluidic channel plate, blood filter layer plate and detection base plate may all be PMMA plates.

[0089] In one example, see Figure 5 The schematic diagram of the structure of a membrane-covered plate is shown. The microfluidic channel plate is connected to the negative pressure element via the membrane-covered plate. The membrane-covered plate defines a first via 59 that connects the detection channel to the negative pressure chamber of the negative pressure element. This first via 59 facilitates the negative pressure element to expel air from the negative pressure chamber via the hollow microneedles in the collection channel, thereby facilitating negative pressure generation during subsequent blood collection.

[0090] Optionally, the above-mentioned covering plate can be made of a flexible material (such as a PDMS film). When the negative pressure element and the microfluidic channel plate clamp the covering plate for fixed connection (such as a fixed connection by screw locking), the sealing between the negative pressure element, the microfluidic channel plate and the covering plate can be effectively achieved.

[0091] PDMS: Polydimethylsiloxane (PDMS) is a common silicone polymer composed of repeating siloxane (-Si-O-Si-) units connected by silicon-carbon bonds. It has the characteristics of low surface tension, high flexibility and elasticity.

[0092] Optional, see Figure 2 A schematic structural diagram of a first pressing plate is shown in FIG. Figure 3 A schematic diagram of the structure of a negative pressure membrane shown in FIG. Figure 4 The structural schematic diagram of a second pressure plate is shown, and the above-mentioned negative pressure element may include a stacked first pressure plate 2, a negative pressure membrane 3 and a second pressure plate 4, and the negative pressure membrane 3 is a self-recovering flexible material (such as a PDMS membrane); the first pressure plate 2 and the second pressure plate 4 cooperate to fix and clamp the negative pressure membrane 3; the middle part of the negative pressure membrane 3 bulges toward the side of the first pressure plate 2 to form a bulge 31, and a negative pressure cavity is formed on the inner side of the bulge 31 (the side opposite to the bulge direction, which is also the side connected to the detection channel), the first pressure plate 2 opens a first gap 21 corresponding to the bulge 31, and the second pressure plate 4 opens a second gap 41 corresponding to the negative pressure cavity.

[0093] Optionally, the raised portion 31 may be hemispherical, with an outer diameter of 23 mm, an inner diameter of 21 mm, and a thickness of 1 mm. At the same time, a raised portion corresponding to the first through hole 59 is provided to communicate with the raised portion 31 .

[0094] Optionally, the diameters of the first clearance 21 and the second clearance 41 may be 23 mm, both corresponding to the clearance spaces provided in the above-mentioned raised portions.

[0095] It can be understood that the raised portion 31 of the negative pressure membrane 3 in the negative pressure element of the present device can be regarded as a button of the negative pressure element, and manual pressing can discharge the air in the negative pressure cavity inside the raised portion 31 .

[0096] Optionally, the first pressing plate 2 and the second pressing plate 4 may be PMMA plates, and the thickness of each may be 4 mm.

[0097] By pressing the raised portion 31 of the negative pressure membrane 3, the air in the negative pressure chamber is evacuated while the second valve core closes the air passage 79, facilitating the subsequent vacuum condition in the blood collection channel. Subsequently, by pushing the raised portion 31, while the first valve core closes the collection channel, blood collected from the storage area is filtered through the blood filter membrane and reaches the detection chip 1 below.

[0098] In one example, see Figure 6 and Figure 5 The microfluidic channel plate has a U-shaped groove on the surface close to the side of the covering plate, and the two ends of the U-shaped groove are respectively connected to the collection channel and the corresponding detection channel; the covering plate is sealed and pressed on the opening side of the U-shaped groove, and the covering plate and the U-shaped groove cooperate to form the microfluidic channel 69.

[0099] Optionally, the cross-sectional dimensions of the U-shaped groove can be a 0.5mm×0.5mm rectangle with a length of 13.5mm. The thickness of the film cover is 1mm, the diameter of the first through hole 59 is 4mm, the corresponding detection channel has a diameter of 4mm, and the collection channel has a diameter of 1mm.

[0100] like Figure 6 and Figure 5 The ends of the U-shaped groove connect the collection channel and the corresponding detection channel, respectively, connecting the collection channel to the membrane-covered plate and the detection channel to the membrane-covered plate. The membrane-covered plate is pressed against the surface of the microfluidic channel plate to achieve a seal. In this way, the U-shaped groove and the membrane-covered plate cooperate to form a microfluidic channel 69.

[0101] In one example, see Figure 7 A first annular groove 711 is provided around the first port of the collection channel on the blood filtering layer plate, and a second annular groove 712 is provided around the second port of the collection channel on the blood filtering layer plate, wherein the first port and the second port are respectively located on two opposite surfaces of the blood filtering layer plate;

[0102] A third annular groove 713 is provided around the third port of the detection channel on the blood filter layer plate, and a fourth annular groove 714 is provided around the fourth port of the collection channel on the blood filter layer plate. The third port and the fourth port are respectively located on two opposite surfaces of the blood filter layer plate;

[0103] The first annular groove 711, the second annular groove 712, the third annular groove 713 and the fourth annular groove 714 are all provided with sealing rubber rings (combined with Figure 7 and Figure 11 The exploded view on the left side of a blood index analysis device, Figure 11 In the figure, a~d are all sealing rubber rings, among which a sealing rubber ring a is provided corresponding to the first ring groove 711, a sealing rubber ring b is provided corresponding to the second ring groove 712, a sealing rubber ring c is provided corresponding to the third ring groove 713, and a sealing rubber ring d is provided corresponding to the fourth ring groove 714), and the thickness of the sealing rubber ring is higher than the depth of the ring groove; in this way, when the microfluidic channel plate and the blood filtration layer plate are fixedly connected, the sealing rubber ring between the two can be pressed to achieve a sealed connection between the collection sub-channel 1 60 and the collection sub-channel 2 70, and a sealed connection between the detection sub-channel 1 610 and the detection sub-channel 2 710. Similarly, when the blood filtration layer plate and the detection base plate are fixedly connected, the sealing rubber ring between the two can be pressed to achieve a sealed connection between the collection sub-channel 2 70 and the collection sub-channel 3 80, and a sealed connection between the detection sub-channel 2 710 and the detection chip 1.

[0104] The third port is covered with a blood filter membrane. The outer circumference of the blood filter membrane is pressed against the inner wall of the third annular groove 713 by a sealant corresponding to the third annular groove 713. The third port is an opening on the surface of the blood filter layer plate near the microfluidic channel plate. This securely fastens the blood filter membrane to the third annular groove 713, completely covering the third port and achieving blood sample filtration.

[0105] The sealing rubber ring of the fourth annular groove 714 surrounds the corresponding working electrode, reference electrode, and counter electrode on the detection chip 1. Thus, during testing, the blood sample, after being filtered through the blood filter membrane, can directly cover the three electrodes (working electrode, reference electrode, and counter electrode) of the detection chip 1, forming a current loop. The three electrodes are connected to the electrochemical detection circuit / analyzer via lead wires, and the concentration of the corresponding indicator is determined based on the electrical signal.

[0106] Optionally, the outer diameter of the sealing rubber rings of the third annular groove 713 and the fourth annular groove 714 provided corresponding to the detection channel may be 8.6 mm, and the inner diameter may be 6.2 mm.

[0107] The detection chip 1 adopts a three-electrode sensor chip, which is a microchip for electrochemical sensing, including a working electrode, a reference electrode and a counter electrode. Among them, the working electrode serves as the main site of the electrochemical reaction, generating a measurable electrical signal for detecting the presence and concentration of target analytes (such as glucose, lactate, heavy metal ions, etc.). The counter electrode is used to complete the circuit loop and maintain the flow of current. The reference electrode is used to provide a stable and known reference potential to ensure the potential control of the working electrode and the accurate measurement of the electrochemical reaction.

[0108] Optionally, the blood filter layer plate in the present application may be provided with a vertically arranged detection area (detection sub-channel 2 710) corresponding to the detection channel, and an air channel 79 with a diameter of 1 mm may be horizontally arranged, and a second valve core groove 77 may be provided perpendicular to the central axis of the air channel 79. The diameter of the second valve core groove 77 may be 2 mm, and the second valve core groove 77 may be embedded in the second valve core. The second valve core may be provided with a second conducting hole with a diameter of 1 mm corresponding to the air channel 79. When controlling the conduction of the air channel 79, the second valve core may be rotated to connect the second conducting hole to the corresponding air channel 79, thereby realizing the connection between the detection channel and the outside of the device through the air channel 79.

[0109] Optionally, the blood filter layer of the present application is provided with a first valve core groove 75 for inserting a first valve core, corresponding to the vertically arranged second collection sub-channel 70. The first valve core groove 75 can have a diameter of 2 mm, and a first conduction hole with a diameter of 1 mm is provided in the first valve core corresponding to the second collection sub-channel 70. When controlling the conduction of the second collection sub-channel 70, the first valve core can be rotated to connect the first conduction hole to the second collection sub-channel 70, thereby achieving conduction of the collection channel.

[0110] Optionally, the blood circulation channel in the device can be anticoagulated with a blood anticoagulant to ensure reliable operation of the device.

[0111] In one example, see Figure 10 A schematic diagram of the combined structure of a blood index analysis device is shown, and Figures 2 to 8 As shown, the microfluidic channel plate is provided with a plurality of screw countersunk holes (see Figure 2 22~29 in), a plurality of screw holes are provided on the negative pressure membrane 3 (see Figure 3 32~39 in), a plurality of screw holes are provided on the second pressing plate 4 (see Figure 4 41~48 in the film-coated plate, multiple screw holes are provided (see Figure 5 51~58 in the microfluidic channel plate is provided with a plurality of screw holes (see Figure 6 61, 62, 63, 64, 66, 68) and screw bottom holes (a screw bottom hole is set for each detection chip 1, namely screw bottom hole 65 and screw bottom hole 67, and a screw through hole 66 is set between the two screws), and multiple screw through holes are set on the blood filter layer (see Figure 7 71, 72, 73, 74, 76, 78 in the third channel) and a plurality of screw bottom holes are provided on the third channel (see Figure 881, 82, 83, 84, 86, 88 in the microfluidic channel plate). In this way, the first short screw passes through 25, 35, 45, and 55 in sequence and then is threadedly connected and fastened with the screw bottom hole 65 on the microfluidic channel plate. The second short screw passes through 27, 37, 47, and 57 in sequence and then is threadedly connected and fastened with the screw bottom hole 67 on the microfluidic channel plate. The first long screw passes through 29, 39, 41, 51, 61, and 71 in sequence and then is threadedly connected and fastened with the screw bottom hole 81 on the detection bottom plate. The first long screw passes through 29, 39, 41, 51, 61, and 71 in sequence and then is threadedly connected with the screw bottom hole 81 on the detection bottom plate. The second long screw passes through 22, 32, 42, 52, and 61 in sequence and then is threadedly connected. 2, 72 and then threadedly connected with the screw bottom hole 82 on the detection base plate, the third long screw passes through 23, 33, 43, 53, 63, 73 in sequence and then threadedly connected with the screw bottom hole 83 on the detection base plate, the fourth long screw passes through 24, 34, 44, 54, 64, 74 in sequence and then threadedly connected with the screw bottom hole 84 on the detection base plate, the fifth long screw passes through 26, 36, 46, 56, 66, 76 in sequence and then threadedly connected with the screw bottom hole 86 on the detection base plate, the sixth long screw passes through 28, 38, 48, 58, 68, 78 in sequence and then threadedly connected with the screw bottom hole 88 on the detection base plate. The side wall of the hollow microneedle 9 is threaded as shown in the figure. Figure 8 The AB glue 87 is fixed to the collection subchannel 3 80 of the detection base plate. The hollow microneedles 9 can be tilted at a certain angle (e.g., 15 degrees) relative to the central axis of the collection subchannel. Thus, the screws in this device are arranged in a circular pattern, ensuring a reliable connection between the first pressure plate 2, negative pressure membrane 3, second pressure plate 4, membrane cover plate, microfluidic channel plate, blood filter layer plate, and detection base plate.

[0112] Optionally, the length of the first pressing plate 2, the negative pressure membrane 3, the second pressing plate 4, the membrane-covering plate, the microfluidic channel plate, the blood filter layer plate and the detection bottom plate may all be 50 mm and 35 mm in width.

[0113] Optionally, the negative pressure membrane 3 and the covering plate can be made by opening a mold, and the mold can be formed by 3D printing technology. The PDMS base resin and the cross-linking agent are mixed in a ratio of 10:1, stirred evenly, and then vacuum degassing is performed using a vacuum pump. The degassed PDMS is poured into the mold and heated and cured for 1 hour.

[0114] Optionally, the first pressing plate 2, the second pressing plate 4, the microfluidic channel plate, the blood filter layer plate and the detection base plate can be processed by a CNC milling machine.

[0115] Based on the above embodiment, see Figure 9The structural diagram of a detection chip shown in the figure, the detection chip 1 can be a three-electrode sensor chip (including a working electrode 11, a reference electrode 12 and a counter electrode 13). The working electrode 11 of the detection chip 1 is pre-coated with an enzyme solution.

[0116] The second end of the detection channel corresponds to the working electrode 11 of the detection chip 1, and the shape of the working electrode 11 corresponds to the port shape setting of the second end of the detection channel. A reference electrode 12 and a counter electrode 13 are arranged around the working electrode 11, and the reference electrode 12 includes a setting corresponding to the shape of the working electrode 11.

[0117] Exemplarily, if the second port of the detection channel is circular, the shape of the working electrode 11 may also correspond to the circle set at the second port of the detection channel. Correspondingly, the reference electrode 12 may be an arc section set corresponding to the working electrode 11.

[0118] In one example, the detection chip 1 can use PET as a substrate material to obtain good mechanical strength and flexibility. First, a cleaning treatment is performed to remove impurities on the surface to ensure the adhesion of the electrode material and the surface cleanliness. The working electrode 11 and the counter electrode 13 are both deposited using conductive graphite, and the electrode structure is etched on the substrate by photolithography and thin film deposition process. Among them, the working electrode 11 can be a circular electrode with a diameter of 3 mm, and the counter electrode 13 can be an arc with a width of 1.2 mm. The reference electrode 12 is prepared from silver / silver chloride material, and a silver layer is deposited on the substrate by electroplating, and then converted into a silver / silver chloride electrode by electrochemical method, so that the electrode has a stable potential and can provide a stable reference signal in electrochemical measurement.

[0119] It can be understood that the installation position 85 of the detection chip 1 is adaptively set according to the size and structure of the detection chip 1 to be installed.

[0120] In one example, the indicators detected by the present application can be blood glucose and lactic acid, and the working electrode 11 of the above-mentioned detection chip 1 is pre-coated with an enzyme solution, and the enzyme solution can be a glucose oxidase solution or a lactate oxidase solution, respectively. Among them, the glucose oxidase solution and the lactate oxidase solution can both be hydroxymethyl ferrocene as a medium, and bovine serum albumin and glutaraldehyde as cross-linking agents. Specifically, glucose oxidase or lactate oxidase is used as the reactant of the working electrode 11, hydroxymethyl ferrocene is used as a medium, the potential required for the reaction is reduced, and an electrocatalytic effect is played, and bovine serum albumin and glutaraldehyde are used as cross-linking agents to achieve the fixation of glucose oxidase and lactate oxidase.

[0121] In one possible configuration scheme, first, 0.3 mg of hydroxymethylferrocene is dissolved in 200 μL of deionized water, ultrasonically treated for 1 minute, and then 0.3 mg of bovine serum albumin and 20 μL of glutaraldehyde (2.5% w / v) are added to obtain a first solution. The first solution is divided into two parts, one part is added with glucose oxidase so that the glucose oxidase concentration is 1000 U / mL, and the other part is added with lactate oxidase so that the lactate oxidase concentration is 500 U / mL. The two enzyme solutions are prepared and can be placed in a refrigerator at 2-8°C for storage. Later, when modifying the working electrode 11, 5 μL of the two enzyme solutions can be taken from each of the two enzyme solutions and applied to the corresponding working electrode 11 to ensure that the electrode is fully covered and then dried and stored in an environment of 2-8°C for subsequent use.

[0122] The detection chip 1 of this application is based on an ampicillin enzyme sensor design. A constant potential is applied to the working electrode 11, allowing a specific enzyme to catalyze the oxidation or reduction reaction of the target analyte. The resulting electron transfer generates a measurable current, thereby achieving sensitive detection. Furthermore, this application also uses hydroxymethylferrocene as a medium, which facilitates ion conduction and signal transmission of the detection chip 1, improving sensitivity and stability.

[0123] The present application utilizes an electrochemical analysis method, utilizing changes in electrochemical signals to react to the concentration of a substance to be measured (e.g., glucose, lactate, cholesterol, etc.). This method has a fast reaction speed and requires a relatively small amount of blood sample, resulting in a small size, low cost, and the advantage of a portable design. Furthermore, the device of the present application incorporates a hollow microneedle 9, which obtains a small amount of blood by puncturing the skin surface. This reduces the pain associated with traditional blood sampling, reduces physiological stimulation to the subject, and allows for the acquisition of a sufficient and stable blood sample.

[0124] Furthermore, the present application can set a corresponding number of microfluidic channels 69 in the device in combination with the number of detection indicators, and each microfluidic channel 69 corresponds to a detection channel and a detection chip 1. Figures 2 to 8 , a device is equipped with two microfluidic channels 69, each corresponding to a detection chip 1 of an indicator. It can realize the simultaneous detection of multiple indicators.

[0125] Based on the above embodiment, see Figures 2 to 11 as well as Figure 12 A schematic diagram of a blood index analysis device is provided. The steps for using the blood index analysis device may be:

[0126] First, the prepared blood glucose detection chip 1 and lactate detection chip 1 are placed in the detection base plate of the device (such as Figure 8) on the mounting position 85 of the two detection chips 1, fasten the blood filter membrane (the blood filter membrane material can be polyethersulfone PES) on the third ring groove 713 through a rubber rubber ring, and cover the blood filter layer plate (such as Figure 7 ) of the detection channel of the detection sub-channel 2 710 of the third port, the various layers of the device are assembled by screws, at this time the first valve core is opened and the second valve core is closed (see Figure 7 , the number of the second valve core corresponds to the number of detection channels), press the button (the raised portion 31 of the negative pressure membrane 3), the air in the button passes through the microfluidic channel 69 and the collection channel, and is finally discharged through the hollow microneedle 9, generating negative pressure in the device.

[0127] Then, insert the hollow microneedle 9 into the arm or other blood collection area, release the button, and the negative pressure in the device will cause the blood to pass through the hollow microneedle 9, the collection channel, the microfluidic channel 69, and finally enter the blood storage area of the detection channel (detection subchannel 610).

[0128] After blood collection is complete, the blood filtration process begins. The first valve core is closed, the second valve core is opened, and the button is pressed. The second valve core is closed before the button is released. This process is designed to generate pressure within the device by pressing the button to assist in filtering the blood sample in the blood storage area through the blood filter membrane. After filtering through the corresponding blood filter membrane, the blood falls into the detection area (detection subchannel 2 710) and onto the three electrodes of the corresponding detection chip 1. After approximately 5 minutes, sufficient blood for testing is collected on the detection chip 1. The leads connecting the three electrodes at the end of the chip are connected to an analyzer or detection circuit. Chronoamperometry is used for testing. The measured current value is compared to the calibration curve used during chip testing to obtain the subject's blood glucose and lactate concentrations. After testing, the first and second valve cores can be opened, allowing the button to return to its original shape through self-healing.

[0129] The chronoamperometry method is to study and measure the kinetic characteristics of electrochemical reactions and the concentration of target analytes by applying a constant potential pulse to the electrode and recording the current response that changes with time.

[0130] It can be understood that the raised portion 31 of the negative pressure membrane 3 in the negative pressure element in this device is regarded as the button of the negative pressure element. By pressing the button and cooperating with the control of the first valve core and the second valve core, the hollow microneedle 9 is used to draw blood. Subsequently, by pressing the button and cooperating with the control of the first valve core and the second valve core, blood filtration processing and electrochemical detection are achieved. Each step is completed in the device, reducing the additional processing and quantification links after blood extraction, and the detection can be completed directly using the electrochemical detection circuit / analyzer.

[0131] The "first" and "second" (if any) in the names mentioned in the embodiments of this application are only used as name identifiers and do not mean the first or second in order.

[0132] Each embodiment in this specification is described in a progressive manner. Similar parts between the embodiments can be referenced. Each embodiment focuses on the differences from other embodiments. Some or all of the modules can be selected according to actual needs to achieve the purpose of the embodiment. Those of ordinary skill in the art can understand and implement it without inventive work.

[0133] The above description is merely an exemplary embodiment of the present application and is not intended to limit the scope of protection of the present application.

Claims

1. A blood index analysis device, characterized in that: include: Hollow microneedles, collection channels, microfluidic channels, detection channels, negative pressure elements and detection chips; The first end of the collection channel is sealed and connected to the hollow microneedle, and the collection channel is connected to the outside through the hollow microneedle; the microfluidic channel is connected to the collection channel and the corresponding detection channel; The first end of the detection channel is connected to the negative pressure element, and the second end of the detection channel corresponds to the sampling area of the detection chip; The collection channel is provided with a first valve core, which is located between the hollow microneedle and the microfluidic channel; the detection channel is provided with an air channel connected to the outside world, and the air channel is provided with a second valve core.

2. The device according to claim 1, characterized in that The detection channel includes a storage area and a detection area that are connected, and the storage area is located above the detection area; The microfluidic channel is connected to the storage area, a blood filter membrane is provided between the storage area and the detection area, and the air channel is connected to the detection area.

3. The device according to claim 1, characterized in that One of the collection channels is connected to multiple microfluidic channels; Each microfluidic channel is connected to a detection channel; Each detection channel corresponds to a detection chip.

4. The device according to any one of claims 1 to 3, characterized in that The collection channel is a through hole that sequentially passes through the microfluidic channel plate, the blood filter layer plate and the detection base plate, and the microfluidic channel plate, the blood filter layer plate and the detection base plate are vertically stacked and fixedly connected; The detection channel is a through hole that sequentially passes through the microfluidic channel plate and the blood filter layer plate, and the detection base plate is provided with a mounting position for the detection chip corresponding to the second end of the detection channel.

5. The device according to claim 4, characterized in that The microfluidic channel plate is connected to the negative pressure element via a membrane plate; The film-covering plate is provided with a first through hole communicating with the detection channel and the negative pressure cavity of the negative pressure element.

6. The device according to claim 5, characterized in that The negative pressure element comprises a stacked first pressure plate, a negative pressure film and a second pressure plate, wherein the negative pressure film is a self-recovering flexible material; The first pressing plate and the second pressing plate cooperate to fix and clamp the negative pressure membrane; The middle part of the negative pressure membrane bulges toward the first pressure plate to form a bulge, and a negative pressure cavity is formed inside the bulge. The first pressure plate opens a first gap corresponding to the bulge, and the second pressure plate opens a second gap corresponding to the negative pressure cavity.

7. The device according to claim 5 or 6, characterized in that The microfluidic channel plate is provided with a U-shaped groove on a surface close to the membrane-covered plate, and the two ends of the U-shaped groove are respectively connected to the collection channel and the corresponding detection channel; The film-covering plate is sealed and pressed on one side of the opening of the U-shaped groove, and the film-covering plate cooperates with the U-shaped groove to form the microfluidic channel.

8. The device according to any one of claims 1-3, 5 and 6, characterized in that: The detection chip is a three-electrode sensor chip, and the working electrodes of the detection chip are pre-coated with an enzyme solution; The second end of the detection channel corresponds to the working electrode, reference electrode and counter electrode of the detection chip. The shape of the working electrode corresponds to the port shape of the second end of the detection channel. The reference electrode and counter electrode are arranged around the working electrode, and the reference electrode corresponds to the shape of the working electrode.

9. The device according to claim 8, characterized in that The enzyme solution is a glucose oxidase solution or a lactate oxidase solution, The glucose oxidase solution and the lactate oxidase solution both use hydroxymethylferrocene as a medium and use bovine serum albumin and glutaraldehyde as cross-linking agents.

10. The device according to claim 8, characterized in that A first annular groove is provided around the first port of the collection channel on the blood filter layer plate, and a second annular groove is provided around the second port of the collection channel on the blood filter layer plate, wherein the first port and the second port are respectively located on two opposite surfaces of the blood filter layer plate; A third annular groove is provided around the third port of the detection channel on the blood filter layer plate, and a fourth annular groove is provided around the fourth port of the collection channel on the blood filter layer plate, wherein the third port and the fourth port are respectively located on two opposite surfaces of the blood filter layer plate; The first ring groove, the second ring groove, the third ring groove and the fourth ring groove are all provided with a sealing rubber ring, and the thickness of the sealing rubber ring is higher than the depth of the ring groove; The third port is covered with a blood filter membrane, the outer periphery of which is pressed against the inner side wall of the third annular groove by a sealing rubber ring corresponding to the third annular groove. The third port is an opening of the blood filter layer plate on a side surface close to the microfluidic channel plate. The sealing rubber ring of the fourth annular groove surrounds the working electrode, reference electrode and counter electrode on the corresponding detection chip.

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