Device for determining concentration of certain ions in blood sample

Abstract

The utility model relates to a device for determining the concentration of certain ions in a blood sample, comprising: a top layer of a membrane (1) capable of filtering out all components in the sample other than plasma; an intermediate layer of glass fibers (2) coated with an ion-selective complex comprising an ionophore (10), a cation exchanger (11) and a dye (12) for promoting the exchange between the certain ions (13) in the plasma and the dye (12); and a bottom layer comprising a millifluid channel (4) along which the dye can travel, where a distance (16) traveled by the dye is indicative of the concentration of the certain ions in the sample.

Description

Technical Field

[0001] The present invention relates to a device for testing the concentration of certain ions in a blood sample. Background Art

[0002] The human body relies on metal ions to perform various biological functions and maintain consistent levels to maintain homeostasis. Regular monitoring of metal ion levels is crucial to ensure the body functions properly. Deviations from ideal levels can lead to health problems and imbalances in bodily functions. Daily monitoring of metal ion levels is recommended to identify any changes early, allowing for prompt treatment and prevention of complications. Currently, clinical measurement of ion concentrations is typically performed using ion-selective electrodes using ionophore-based membranes. While reliable, this method requires specialized equipment and is not practical in low-resource settings.

[0003] In their paper titled “Ionophore-Based Ion-Selective Potentiometric and Optical Sensors,” R. Daniel Johnson et al. describe ion-selective electrodes (ISEs) and optodes, focusing on the basic mechanisms, response characteristics, and recognition elements (ionophores) described so far for these sensors.

[0004] In their paper titled “Ion Selective Optodes: from the Bulk to the Nanoscale,” Xiaojiang Xie et al. describe recent progress in miniaturizing ion-selective optodes into micro- and nanoscale sensors.

[0005] Nevertheless, none of the aforementioned papers discloses an easy-to-use and convenient solution for detecting certain ions in blood samples that can be used in low-resource settings. Summary of the Invention

[0006] The above-mentioned disadvantages and difficulties are overcome by the present invention as described in detail in the following paragraphs.

[0007] One aspect of the present invention provides an apparatus for determining the concentration of certain ions in a blood sample, comprising: a top membrane layer capable of filtering out all components in the sample except plasma; a middle glass fiber layer coated with an ion-selective complex, the complex comprising an ion carrier, a cation exchanger, and a dye for facilitating the exchange between the certain ions in the plasma and the dye; and a bottom layer comprising a millifluidic channel along which the dye can travel, wherein the distance traveled by the dye indicates the concentration of the certain ions in the sample.

[0008] Advantageously, the device integrates the separation of plasma from the sample, the detection of certain ions in the plasma, and the indication of ion concentration into a single step, thereby eliminating the need for solution transfers and making the process more convenient and efficient.

[0009] Advantageously, the device simplifies and speeds up the ion detection process, making it more efficient.

[0010] Advantageously, the device also provides greater accuracy and convenience in detecting ion concentrations in blood samples.

[0011] Advantageously, the device provides distance-based analysis using a pH-independent millifluidic channel and a direct ion exchange process using a pH-insensitive dye. Unlike conventional optodes based on pH indicators, the device operates without the participation of H+ ions in an ion exchange equilibrium. Therefore, the device's test results are unaffected by changes in the sample's pH. Being pH-independent, the device is more reliable and versatile in providing accurate and consistent analysis across diverse applications, regardless of the sample's pH conditions.

[0012] Typically, the concentration of ions is measured in vitro.

[0013] Advantageously, the device requires only a single drop of blood sample and is therefore very convenient for point-of-care testing. More specifically, the device eliminates the need for using laboratory equipment to perform blood tests.

[0014] Typically, the composite material is coated onto glass fibers with a polymer binder.

[0015] Typically, the bottom layer comprises a polymer sheet on which the channels are disposed, the channels being coated with silica gel powder to help retain the dye-laden plasma within the channels.

[0016] Advantageously, TLC microfluidic channels ensure that the liquid is well contained within the channel, thereby allowing the liquid to flow better along the channel and providing more accurate and efficient results.

[0017] Advantageously, the membrane can quickly and efficiently separate plasma from blood for on-site analysis, thus eliminating the need for time-consuming centrifugation.

[0018] Advantageously, the device provides a convenient and cost-effective solution for point-of-care testing and is a promising device for use in low-resource settings.

[0019] In one embodiment, the apparatus further comprises two annular members, each annular member being disposed between any two adjacent layers to separate one layer from another.

[0020] Typically, the bottom layer includes two marks indicating a lower limit and an upper limit of the distance within which the concentration of the certain ions in the sample is considered normal.

[0021] In another embodiment, the device further comprises a cover arranged on top of the layer, wherein the cover comprises: a hollow portion through which the distance is visible; another hollow portion aligned with the membrane through which the sample can be dropped onto the membrane; and two marks indicating a lower limit and an upper limit of the distance within which the ion concentration in the sample is considered normal.

[0022] Generally, by varying the combination of the ionophore, dye, and cation exchanger, the complex can be tailored to facilitate the exchange of certain ions in plasma with the dye.

[0023] Typically, the dye is fluorescent and the cation exchanger is lipophilic.

[0024] Typically, the device is portable and can be used at the point of care.

[0025] Advantageously, the device is configured in a self-contained manner and is therefore easy to use and practical.

[0026] Another aspect of the invention provides a set of devices, each device being a device as described in the preceding paragraphs, wherein each complex of the device is customized to facilitate the exchange between a different ion in plasma and the dye.

[0027] Advantageously, the set or device provides a quick and simple way to determine various medical conditions and is therefore invaluable to medical professionals and researchers. DETAILED DESCRIPTION

[0028] The present invention will now be described in more detail by way of example with reference to the accompanying drawings, in which:

[0029] Figure 1 is an exploded view of a kit for testing the concentration of certain ions in a blood sample according to the present invention;

[0030] Figure 2 shows the mechanism according to the present invention by which certain ions of a blood sample are captured by an ionophore coated on a glass fiber while a dye is released from the ionophore;

[0031] Figure 3 shows reference markers according to the present invention that define the range within which ion concentrations in a blood sample are considered normal; and

[0032] Figure 4A kit according to the present invention is shown that is capable of detecting a single type of ion (left) and multiple types of ions (right) in a single step.

[0033] See also Figure 1 The kit includes three main components: a plasma separation membrane 1, a glass fiber mat 2 coated with an ion-selective complex, and a polymer plate 3 on which thin-layer chromatography ("TLC") millifluidic channels 4 are arranged. The polymer can be Teflon. A ring 5 is arranged between the membrane 1 and the glass fiber mat 2, and another ring 6 is arranged between the glass fiber mat 2 and the polymer plate 3 to provide a space between the membrane 1, the glass fiber mat 2, and the polymer plate 3. A cover 7 is arranged on top of the membrane 1. The cover 7 includes: a hollow portion 8 through which the channel 4 is visible; and another hollow portion 9 aligned with the membrane 1, through which a blood sample can be dropped onto the membrane 1.

[0034] The kit requires a drop of blood sample to detect certain ions in the sample and indicate their concentration. When in use, a drop of sample is dropped onto the membrane 1. Capillary action and gravity help transfer the sample from the top of the membrane 1 to the channel 4, thereby indicating the ion concentration in the sample.

[0035] Plasma separation membrane 1 allows only the plasma of a sample to pass through, filtering out other sample components. Membrane 1 is made of a thin polymer material with a controlled pore size that allows only plasma to pass through while retaining other blood components such as red blood cells and platelets. Membrane 1 is constructed in such a way that capillary action and gravity are sufficient to replace the conventional centrifugal force required to separate plasma from a blood sample.

[0036] See also Figure 2The ion-selective complex coated on the glass fiber mat 2 includes a combination of an ionophore 10, a lipophilic cation exchanger 11, and a fluorescent dye indicator 12. More specifically, the ionophore can be a potassium ionophore, a sodium ionophore, a calcium ionophore, or a magnesium ionophore, the cation exchanger can be tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, and the dye indicator can be Nile Blue A or Basic Yellow 1. The ionophore 10 provides excellent selectivity in capturing specific ions 13 from plasma while simultaneously triggering the release of the dye molecule 12 from the complex. This specificity arises from the ionophore 10's ability to discriminate between ions, enabling it to capture only the ions of interest 13 and ignore other ions. The coating enables quantitative ion-dye replacement, in which certain ions in the plasma are replaced by a fluorescent dye in a quantifiable manner. By incorporating ionophores with high ion selectivity into the coating, specific ions in the sample can be targeted. By manipulating the combination, the coating on the glass fiber mat 2 provides the flexibility to selectively capture specific ions 13 from the plasma, thereby enabling the identification of target ions in the sample, such as potassium, sodium, magnesium, or calcium.

[0037] See also Figure 4 The reagent kit 14 on the left is configured to detect a single type of ion in a blood sample, while the reagent kit set 15 on the right includes multiple reagent kits, each configured to detect a different type of ion in a blood sample. This configuration is achieved by varying the combination of the ion carrier, cation exchanger, and dye indicator in the ion-selective complex.

[0038] The process of coating the ion-selective complex onto the fiberglass mat involves the use of a polymer binder, such as plasticized polyvinyl chloride or polyacrylamide, or polyurethane. This binder helps hold the complex in place on the mat, ensuring it remains stable and functional. The coating process helps ensure that the ion-selective complex is evenly distributed across the mat's surface, ensuring that the ions effectively interact with the electrode surface, making the overall process highly efficient.

[0039] The coating achieves high selectivity in mixed or separate solutions of monovalent and divalent ions and can be sustainably produced without toxic solvents. This coating has the potential to revolutionize ion detection by offering a more environmentally friendly and efficient approach compared to conventional methods.

[0040] like Figure 1As shown, the TLC millifluidic channel 4 is used to quantitatively measure the concentration of ions. The fabrication of the TLC millifluidic channel 4 includes the following steps: drilling a millifluidic channel on a polymer plate 3; and coating the millifluidic channel with silica gel powder to transform the millifluidic channel into a TLC millifluidic channel 4. Compared to conventional wax-printed channels, this special design significantly improves the water retention and liquid diffusion capabilities of the channel. When the dye comes into contact with the millifluidic channel, it is absorbed onto the surface of the silica. Figure 3 As shown, the concentration of certain ions in a sample can be determined by measuring the distance 16 covered by the dye, because the length the dye travels is proportional to the concentration of the ion in the sample. A longer distance indicates a higher ion concentration. Thus, the TLC millifluidic channel converts ion concentration into a distance-based measurement that is not only precise and accurate, but also easy to interpret. Distance 16 indicates the amount of dye released from the complex, which accurately quantifies the concentration of the ion in the sample.

[0041] See also Figure 3 The test kit comes with two reference marks 17 and 18, which serve as guides for determining whether the ion levels in the blood sample are normal. Reference marks 17 and 18 are visual indicators that help healthcare providers accurately interpret the test results. If the distance 16 covered by the dye falls within the marks 17 and 18, it indicates that the ion levels in the blood sample are within the acceptable range. Conversely, if the distance covered by the dye falls outside the marks 17 and 18, it indicates that further evaluation may be necessary to identify any underlying health issues or conditions. Therefore, the test results can be used to diagnose certain medical conditions and monitor the progression of diseases.

[0042] The kit provides a simple, efficient, and accurate method to indicate ion concentrations in blood samples. The kit can identify and isolate specific ions, which can aid in the diagnosis and treatment of related diseases.

[0043] The kit allows for easy determination of ion concentrations in blood samples, unlike the complex procedures required by ICP-MS / OES. The latter requires expensive testing equipment, trained personnel for sample collection and analysis, and complex sample pretreatment. In contrast, the kit provides a straightforward solution that accurately measures ion concentrations in samples.

[0044] Unlike conventional pH-sensitive optode sensors, the kit provides distance-based analysis using a pH-independent TLC millifluidic channel due to a simple ion exchange process and the use of a pH-insensitive dye as an indicator. When the kit is used to test the concentration of certain ions in a blood sample, the ion exchange equilibrium does not involve H+ ions, which distinguishes it from conventional hydrogen chromophores or pH-indicator-based optodes. Therefore, it can be expected that the readout signal obtained from the distance-based analysis will not be affected by changes in the solution pH. This feature provides a reliable and consistent analytical platform, enabling accurate measurements regardless of pH conditions. The combination of a simple ion exchange process and the use of a pH-insensitive dye enhances the robustness and versatility of the kit.

[0045] It will be understood by those skilled in the art that the present invention may also include further additional modifications that do not affect its overall functionality.

Claims

1. A device for determining the concentration of certain ions in a blood sample, characterized in that The device comprises: Membrane (1) top layer, capable of filtering out all components of the sample except plasma; an intermediate layer of glass fiber (2) coated with an ion-selective complex comprising an ion carrier (10), a cation exchanger (11) and a dye (12) for promoting the exchange between the certain ions (13) in plasma and the dye (12); and A bottom layer comprising a millifluidic channel (4) along which the dye can travel, wherein the distance (16) traveled by the dye is indicative of the concentration of the certain ions in the sample.

2. The device according to claim 1, wherein The composite is coated on the glass fiber (2) by a polymer binder.

3. The apparatus of claim 2, wherein: The bottom layer comprises a polymer plate (3), the channel (4) is arranged on the polymer plate, and the channel (4) is coated with silica gel powder to promote the retention of the plasma carrying the dye in the channel (4).

4. The apparatus according to claim 3, further comprising two annular members (5, 6), each annular member being arranged between any two adjacent layers to separate one layer from another.

5. The apparatus of claim 4, wherein: The bottom layer includes two markings (17, 18) indicating the lower and upper limits of the distance (16) within which the concentration of the certain ions in the sample is considered normal.

6. The device of claim 4, further comprising a cover (7) arranged on top of the layer, wherein the cover (7) comprises: a hollow portion (8), through which the distance (16) is visible; another hollow portion (9) aligned with the membrane (1), through which the sample can be dropped onto the membrane (1); as well as Two marks (17, 18) indicate the lower and upper limits of the distance (16) within which the concentration of the ion in the sample is considered normal.

7. The apparatus of claim 6, wherein: By varying the combination of the ionophore (10), dye (12), and cation exchanger (11), the complex can be tailored to facilitate the exchange between certain ions (13) in the plasma and the dye (12).

8. The apparatus of claim 7, wherein: The dye (12) is fluorescent and the cation exchanger (11) is lipophilic.

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