A device for real-time monitoring of ion types and ion concentrations in blood purification wastewater

Abstract

The present invention relates to the field of biosensor technology, and discloses a device for real-time monitoring of ion types and ion concentrations in blood purification wastewater, which is composed of a substrate, a source line, a gate line, a semiconductor layer, a drain line, a packaging layer, a solid electrolyte layer, and an ion selective layer, and is prepared in a stacking manner. The present invention can avoid mutual interference among multiple ions and realize portable, highly sensitive, highly selective, and highly reliable online detection.

Description

Technical Field

[0001] The present invention relates to the field of biosensor technology, in particular to a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid. Background Art

[0002] Blood purification is one of the most commonly used extracorporeal life support treatments for patients with acute kidney injury and chronic renal failure. The dialysate and replacement fluid in blood purification therapy help remove toxic metabolites and excess fluid from the patient's blood through the circulation exchange of the dialyzer / filter. More importantly, it helps maintain the concentration of multiple ions in the blood at a physiological state, which is similar to the function of healthy kidneys. In order to maintain safe and effective treatment during blood purification, the blood ions (such as Na+, + , K + and Ca 2+ ) concentration, adjust the dialysate / replacement fluid ratio in real time, master the progress and effect of blood purification, improve clinical treatment effects, avoid overtreatment or medical accidents, etc. Especially when performing local citrate anticoagulation, it is necessary to frequently measure the Ca in the blood before and after the dialyzer / filter. 2+ Concentration assessment is necessary to ensure the effectiveness and safety of local citrate anticoagulation. However, multiple ion concentration monitoring not only consumes blood in the human body, but also leads to frequent interruptions of blood purification treatment.

[0003] The composition and concentration of the therapeutic wastewater from blood purification are similar to those in serum / blood, mainly including inorganic anions and cations, and their normal concentration ranges are Na + 135 to 145 mM, K + 3.5 to 5.5 mM Ca 2+ 1.13 to 1.35 mM (Ca during local citrate anticoagulation) 2+ 0.25 to 0.5 mM), ion type and concentration detection in blood purification waste liquid is an important evaluation criterion for the effect of blood purification treatment, which helps to maintain the optimal treatment program and avoid excessive monitoring without collecting additional blood samples from patients. Real-time detection of multi-ion concentrations in blood purification treatment waste liquid is of great significance.

[0004] At present, the detection methods of ion types and concentrations in blood purification wastewater can be determined by Roche electrolyte analyzer (based on ISE) or i-STAT blood gas analyzer, both of which are costly and time-consuming. Therefore, for the detection of multi-ion concentrations in blood purification treatment wastewater, an ion sensor with simple operation, fast detection speed, high sensitivity and accuracy is urgently needed.

[0005] At present, the ion detection technology of blood purification wastewater faces the following difficulties: First, multiple ions interfere with each other, and it is impossible to exclude the influence of other ions on the detection of target ion concentration, and the influence of other complex components such as proteins on the detection results. Second, the detection instruments currently used are large medical detection equipment, and portable high-sensitivity, high-selectivity, and high-reliability online detection still faces huge challenges.

[0006] In view of this, this application is hereby filed. Summary of the invention

[0007] In order to solve the shortcomings of the current ion detection technology for blood purification waste liquid, the first aspect of the present invention provides a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid, including: a sensing probe and a driving detection circuit; the sensing probe includes a sensing area and a wire area; the sensing area is connected to the wire area, the sensing area is located at the head of the sensing probe, and the wire area is located in the middle and rear of the sensing probe; the sensing probe includes a substrate, a gate line and a plurality of source lines are arranged on the substrate, the gate line and the plurality of source lines all cross the sensing area and the wire area, the gate line is located in the middle of the substrate, and the plurality of source lines are located on both sides of the gate line; each source line is covered with a semiconductor layer above one end of the sensing area; a drain line is arranged between two adjacent source lines and between the source line and the gate line, the drain line is a strip structure, the drain line includes a front section and a rear section, the front section The segments are arranged above the semiconductor layer, the front segment is perpendicular to the source line and forms an intersection area with the source line, and the rear segment is parallel to the source line and crosses the sensing area and the wire area; the gate line is located at one end of the wire area, each source line is located at one end of the wire area, and each drain line is located at one end of the wire area, and they are all connected to the drive detection circuit; the gate line, multiple source lines and multiple drain lines are covered with a packaging layer, and a first square hole and a plurality of second square holes are opened on the packaging layer, one end of the gate line located in the sensing area is located in the first square hole, the second square hole corresponds to the semiconductor layer one by one, the semiconductor layer and the intersection area are both located in the second square hole, and the side length of the second square hole is: 3µm~230µm; a solid electrolyte layer is arranged above the packaging layer, and the solid electrolyte layer covers the multiple second square holes; the solid electrolyte layer is covered with an ion selection layer.

[0008] Furthermore, the intersection area is a square, and the side length of the intersection area is 2µm~200µm; the width of the source line is 2µm~200µm; the width of the drain line is 2µm~200µm.

[0009] Furthermore, the material of the substrate is one of glass, silicon wafer, polyethylene terephthalate PET, polyethylene naphthalate PEN, polydimethylsiloxane PDMS, PMMA, PI, polyurethane PU and polystyrene-ethylene-butylene SEBS.

[0010] Furthermore, the material of the source line is one of gold, platinum, carbon nanotubes and graphene, the material of the drain line is one of gold, platinum, carbon nanotubes and graphene, and the material of the gate line is one of gold, silver, silver / silver chloride, poly (3,4-ethylenedioxythiophene): polystyrene sulfonate, carbon nanotubes, graphene and graphyne.

[0011] Furthermore, the material of the semiconductor layer is one of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly[2,5-bis(2,5,8,11,14-pentaoxa-16)-3,6-bis(thiophene-2)-2,5-dihydropyrrole (3,4)pyrrole-1,4-dione], poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly(benzimidazole dibenzophenanthroline) and polyethylene glycol (diol) diacrylate. The molecular formula of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 28 H 36 O8S4]N, the molecular formula of poly[bithiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 26 H 34 O8S3]N, the molecular formula of poly (benzimidazole dibenzophenanthroline) is (C 20 H6N4O2) n , the molecular formula of polyethylene glycol (diol) diacrylate is (C2H4O) n C6H6O3.

[0012] Furthermore, the thickness of the semiconductor layer is 10nm~200nm; the semiconductor layer is square, and the side length of the semiconductor layer is 3µm~220µm; the width of the source line and the width of the drain line are both smaller than the side length of the semiconductor layer.

[0013] Furthermore, the material of the encapsulation layer is one of Parylene-C, cellulose, photoresist SU-8, polystyrene, polydimethylsiloxane PDMS and polystyrene-ethylene-butylene SEBS.

[0014] Furthermore, the driving detection circuit is integrated into a chip with a size of 20 mm×20 mm.

[0015] The second aspect of the present invention provides a method for preparing a device for real-time monitoring of ion types and ion concentrations in blood purification wastewater, comprising the following steps: making a substrate into the shape of a sensing probe; dividing a sensing area and a wire area on the substrate; preparing a gate line in the middle of the substrate; preparing a plurality of source lines parallel to the gate line on both sides of the gate line on the substrate, so that the gate line and the plurality of source lines span the sensing area and the wire area; covering a semiconductor layer above one end of each source line located in the sensing area; preparing a drain line between two adjacent source lines and between the source line and the gate line; wherein the drain line is a strip structure, the drain line includes a front section and a rear section, the front section is arranged above the semiconductor layer, the front section is perpendicular to the source line and forms an intersection with the source line The invention relates to a method for forming a gate line, a plurality of source lines and a plurality of drain lines, wherein the gate line, the plurality of source lines and the plurality of drain lines are covered with a packaging layer; a first square hole and a plurality of second square holes are provided on the packaging layer, so that one end of the gate line located in the sensing area is located in the first square hole, and the semiconductor layer and the crossing area are both located in the second square hole, and the side length of the second square hole is 3µm to 230µm; a solid electrolyte layer is provided above the packaging layer, so that the solid electrolyte layer covers the plurality of second square holes; an ion selection layer is covered above the solid electrolyte layer; a driving detection circuit is prepared; and one end of the gate line located in the wiring area, one end of each source line located in the wiring area and one end of each drain line located in the wiring area are all connected to the driving detection circuit.

[0016] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0017] 1. It can realize the simultaneous detection of multiple ions in blood purification wastewater by preparing ion selection layers in different areas of the sensing area, and by measuring the difference in the output current of the sensor array for ions of different concentrations, the final ion concentration can be calculated.

[0018] 2. It can be miniaturized and run sustainably with low power consumption. The multi-ion sensor probe array and the drive measurement circuit can be prepared on a 20mm×20mm chip. The current is 10µA in the dormant state and it can work continuously for more than 15 days. The test results and drive instructions can communicate with mobile devices via Bluetooth to achieve online monitoring and timely feedback.

[0019] 3. The probe sensing area can be directly inserted into the liquid to be tested to achieve plug-in rapid detection.

[0020] 4. The number of devices in the probe array can be changed by changing the number of source lines and drain lines to meet different detection requirements.

[0021] 5. Different ions can be detected by changing the corresponding ion carriers in the ion selective membrane, which greatly reduces the production and design costs and improves the preparation efficiency of ion sensors.

[0022] 6. The drive measurement circuit can quickly adapt to the probe arrays with different drive measurement requirements by changing the selection of electronic components and the arrangement of interface probes.

[0023] 7. Different power supply interfaces can be prepared according to the situation, and various power supply modes such as button batteries, NFC, solar energy, etc. can be selected. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0025] Figure 1 It is a top view of a first device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0026] Figure 2 is a top view of a second device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0027] Figure 3 is a cross-sectional view of a needle tip sensing area of ​​a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0028] Figure 4 It is a three-dimensional structural diagram of a needle tip sensing area of ​​a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0029] Figure 5a It is a structural diagram of a substrate in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0030] Figure 5b It is a schematic diagram of the structural relationship between a substrate, a gate line and a source line in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0031] Figure 5c It is a schematic diagram of the structural relationship between a substrate, a gate line, a source line and a semiconductor layer in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0032] Figure 5dIt is a schematic diagram of the structural relationship between a substrate, a gate line, a source line, a semiconductor layer and a drain line in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0033] Figure 5e It is a schematic diagram of the structural relationship after a substrate, a gate line, a source line, a semiconductor layer and a drain line are covered with a packaging layer in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0034] Figure 5f It is a schematic diagram of the structural relationship after a solid electrolyte layer is covered on a packaging layer in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0035] Figure 5g It is a schematic diagram of the structural relationship after the ion selection layer is covered on the solid electrolyte layer in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0036] Figure 6 It is a circuit structure diagram of a driving detection circuit in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by an embodiment of the present invention;

[0037] Figure 7 The current transfer characteristic curve of the needle tip sensing area of ​​the device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by the embodiment of the present invention when the needle tip sensing area does not contain a solid electrolyte layer and an ion selective layer, contains only an ion selective layer, and contains both a solid electrolyte layer and an ion selective layer;

[0038] Figure 8 is a transfer characteristic curve of the current of different ions and different concentrations of the probe under the sodium ion selective layer provided by an embodiment of the present invention;

[0039] Fig. 9 is a transfer characteristic curve of the current of the probe under the potassium ion selective layer to different ions and different concentrations provided by an embodiment of the present invention;

[0040] Fig.10 is a transfer characteristic curve of the current of the probe under the calcium ion selective layer to different ions and different concentrations provided by an embodiment of the present invention;

[0041] Fig.11a is a comparison diagram of the difference between the sodium ion detection using the device provided in the embodiment of the present invention and the Roche detection;

[0042] Fig.11b This is a comparison diagram of the difference between the detection of potassium ions using the device provided in the embodiment of the present invention and the Roche detection;

[0043] Fig.11c is a comparison diagram of the difference between the detection of calcium ions using the device provided in the embodiment of the present invention and the Roche detection;

[0044] Fig.12 is a schematic diagram of the structural formula of p(g2T-TT) provided in an embodiment of the present invention;

[0045] Fig.13 is a schematic diagram of the structural formula of Homo-gDPP provided in an embodiment of the present invention;

[0046] Fig.14 is a schematic diagram of the structural formula of p(g2T-T) provided in an embodiment of the present invention;

[0047] Fig.15 is a schematic structural diagram of a BBL provided by an embodiment of the present invention;

[0048] Fig.16 It is a schematic diagram of the structural formula of PEGDA provided in an embodiment of the present invention.

[0049] Marks and corresponding parts names in the attached drawings:

[0050] 1-substrate, 2-source line, 3-gate line, 4-semiconductor layer, 5-drain line, 6-encapsulation layer, 7-solid electrolyte layer, 8-ion selection layer. DETAILED DESCRIPTION

[0051] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments and drawings. The exemplary embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention.

[0052] In the following description, a large number of specific details are set forth in order to provide a thorough understanding of the present invention. However, it is apparent to one of ordinary skill in the art that these specific details are not necessarily employed to practice the present invention. In other embodiments, in order to avoid obscuring the present invention, well-known structures, circuits, materials, or methods are not specifically described.

[0053] Throughout the specification, references to "one embodiment," "an embodiment," "an example," or "an example" mean that a particular feature, structure, or characteristic described in conjunction with the embodiment or example is included in at least one embodiment of the present invention. Therefore, the phrases "one embodiment," "an embodiment," "an example," or "an example" appearing in various places throughout the specification do not necessarily all refer to the same embodiment or example. In addition, particular features, structures, or characteristics may be combined in one or more embodiments or examples in any suitable combination and / or sub-combination. In addition, it will be appreciated by those of ordinary skill in the art that the figures provided herein are for illustrative purposes and that the figures are not necessarily drawn to scale. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0054] In the description of the present invention, the directions or positional relationships indicated by terms such as “front”, “rear”, “left”, “right”, “up”, “down”, “vertical”, “horizontal”, “high”, “low”, “inside” and “outside” are based on the directions or positional relationships shown in the accompanying drawings and are only for the convenience of describing the present invention and simplifying the description. They do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction. Therefore, they should not be understood as limiting the scope of protection of the present invention.

[0055] Example: Figure 1 and Figure 2 As shown, this embodiment provides two top views of devices for real-time monitoring of ion types and ion concentrations in blood purification wastewater. Figure 1 The first device for real-time monitoring of ion types and ion concentrations in blood purification wastewater is an independent source-drain, common gate, Figure 2 The first device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid is shown as a common gate, drain, and independent source. The above two devices for real-time monitoring of ion types and ion concentrations in blood purification waste liquid have the following common structural features.

[0056] like Figure 3 and Figure 4 As shown, the device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid is composed of a sensing probe and a driving detection circuit. The sensing probe is composed of a substrate 1, a source line 2, a gate line 3, a semiconductor layer 4, a drain line 5, a packaging layer 6, a solid electrolyte layer 7 and an ion selection layer 8, and is designed in a stacked manner.

[0057] Substrate 1 Figure 5aAs shown, a probe-shaped substrate is shown, and the material of the substrate can be selected from one of glass, silicon wafer, polyethylene terephthalate PET, polyethylene naphthalate PEN, polydimethylsiloxane PDMS, PMMA, PI, polyurethane PU and polystyrene-ethylene-butylene SEBS. In this embodiment, the substrate is pre-divided into a sensing area located at the probe head (needle tip) and a wire area located in the middle and rear of the probe.

[0058] like Figure 5b As shown, from a top view, in a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided by this embodiment, a gate line 3 and 6 source lines 2 are arranged on the substrate 1, and the source line 2 and the gate line 3 are both strip structures, wherein the width of the source line 2 is 2µm~200µm. From the arrangement point of view, the gate line 3 and the 6 source lines 2 both span the sensing area and the wire area, the gate line 3 is located in the middle of the substrate 1, and there are 3 source lines 2 on both sides of the gate line 3 at equal intervals, and each source line 2 is independently divided into a source electrode in the sensing area, and each source line 2 is parallel to the gate line 3 in the wire area. In terms of material selection, the material of the source line 2 can be selected from one of gold, platinum, carbon nanotubes and graphene, and the material of the gate line 3 can be selected from one of gold, silver, silver / silver chloride, poly 3,4-ethylenedioxythiophene: polystyrene sulfonate, carbon nanotubes, graphene and graphyne.

[0059] like Figure 5c As shown, a semiconductor layer 4 is disposed above one end of each source line 2 located in the sensing area. The semiconductor layer 4 is square, with a side length of 3µm to 220µm and a thickness of 10nm to 200nm. Figure 5c It can be seen that the width of each source line 2 is less than the side length of the corresponding semiconductor layer 4. In terms of material selection, the material of the semiconductor layer 4 can be selected from one of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly[2,5-bis(2,5,8,11,14-pentaoxa-16)-3,6-bis(thiophene-2)-2,5-dihydropyrrole (3,4)pyrrole-1,4-dione], poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly(benzimidazole dibenzophenanthroline) and polyethylene glycol (diol) diacrylate. Among them, the molecular formula of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 28 H 36 O8S4]N, usually called p(g2T-TT), the structural formula of p(g2T-TT) is as follows Fig.12As shown; Poly[2,5-bis(2,5,8,11,14-pentaoxa-16)-3,6-bis(thiophene-2)-2,5-dihydropyrrole(3,4)pyrrole-1,4-dione] is Homo-gDPP, and the structural formula of Homo-gDPP is as follows Fig.13 As shown; the molecular formula of poly[bithiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 26 H 34 O8S3]N, usually called p(g2T-T), the structural formula of p(g2T-T) is Fig.14 As shown; the molecular formula of poly (benzimidazole dibenzophenanthroline) is (C 20 H6N4O2) n , usually called BBL, the structural formula of BBL is as follows Fig.15 As shown; the molecular formula of polyethylene glycol (diol) diacrylate is (C2H4O) n C6H6O3, commonly known as a mixture of PEGDA, the structural formula of PEGDA is as follows Fig.16 The above materials are all existing materials.

[0060] like Figure 5d As shown, a drain line 5 is arranged between two adjacent source lines 2 and between the source line 2 and the gate line 3, for a total of 6 drain lines 5. Each drain line 5 is a strip structure as a whole, and its width is 2µm~200µm. Each drain line 5 is divided into a front section and a rear section. From a top view, the front section is arranged above the semiconductor layer 4 to form a drain electrode. It should also be noted that the width of each drain line 5 is also smaller than the side length of the corresponding semiconductor layer 4. Furthermore, the front section is perpendicular to the source line 2, and a square intersection area with a side length of 2µm~200µm is formed between the two. The intersection area constitutes a single probe device, and each probe device is used to detect a single ion (such as Na + , K + and Ca 2+ ). The rear section is parallel to the source line 2 and crosses the sensing area and the wire area. In terms of material selection, the material of the drain line 5 can be selected from one of gold, platinum, carbon nanotubes and graphene.

[0061] like Figure 5eAs shown, an encapsulation layer 6 is covered above the gate line 3, the six source lines 2 and the six drain lines 5. A first square hole is provided on the encapsulation layer 6, and one end of the gate line 3 located in the sensing area is located in the first square hole. Six second square holes are provided on the encapsulation layer 6, and the six second square holes correspond to the six semiconductor layers 4 one by one, so that the semiconductor layer 4 and the intersection area are both located in the second square hole, and the side length of the second square hole is: 3µm~230µm. In terms of material selection, the material of the encapsulation layer 6 can be selected from one of Parylene-C, cellulose, photoresist SU-8, polystyrene, polydimethylsiloxane PDMS and polystyrene-ethylene-butylene SEBS.

[0062] like Figure 5f As shown, a solid electrolyte layer 7 is disposed above the encapsulation layer 6 , and the solid electrolyte layer 7 covers the six second square holes and exposes the first square holes.

[0063] like Figure 5g As shown, an ion selection layer 8 is provided in the working area above the solid electrolyte layer 7. The ion selection layer 8 is an ion selective membrane. It should be noted that the intersection of the source line and the drain line is the working area. The structure contains four working areas, each of which is far apart. The corresponding ion selection layer can be prepared on the top by drop coating.

[0064] The drive detection circuit is a prior art, and its specific circuit structure is referenced Figure 6 , including: power supply module, control module, measurement module and Bluetooth module. The drive detection circuit is integrated in a chip with a size of 20mm×20mm. In terms of the connection relationship with the sensor probe, one end of the gate line 3 located in the wire area, one end of each source line 2 located in the wire area, and one end of the rear section of each drain line 5 located in the wire area are all connected to the drive detection circuit. The interaction is completed by applying voltage to the drain and the gate and reading the source current; fully automatic wake-up measurement and sleep can be achieved. After reading the data of a single device in the probe array each time, the results of each device in the array are integrated and the real types of ions (such as Na + , K + and Ca 2+ )concentration.

[0065] In summary, the above-mentioned device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid provided in this embodiment, the external circuit interacts with all devices in the probe array, and the interaction is to realize the gating control and reading operation of any probe device by defining the combination of rows and columns, and drive a single probe device by applying gate and drain voltages, and obtain a readable voltage signal through source current collection and transconductance amplification; the external circuit also has the ability to configure logic code, and can flexibly change the gating interface according to different detection requirements to realize the gating control and reading of specific probe devices, so as to achieve the effect of probe array signal collection. It is possible to realize the simultaneous detection of multiple ions in blood purification waste liquid, by preparing Na on different areas of the sensing area + , K + and Ca 2+ The selection layer is determined by measuring the sensitivity of the sensor array to different concentrations of Na + , K + and Ca 2+ The output current difference is used to calculate the final ion concentration, for example, Na + The final concentration of Na + The device response current under the selection layer is subtracted from its K + and Ca 2+ At the same time, the device has high stability, high sensitivity and repeatability), and can achieve an ultra-high maximum transconductance (gm) of 58.0mS, respectively Na + (14.0mA / dec)、K + (1.73 mA / dec) and Ca 2+ (4.09mA / dec) provides ultra-high current sensitivity. Based on the results of the traditional Roche detection method, Na + , K + and Ca 2+ The differences in the accuracy of the tests did not exceed 1.0%, 2.2%, and 18.5%, respectively.

[0066] The preparation method of the above-mentioned device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid is:

[0067] Step 1: Use isopropyl alcohol to ultrasonically clean the substrate for 15 minutes, and then treat the flexible circuit board in ultraviolet ozone for 15 minutes. In this step, a silicon wafer substrate is used as the substrate.

[0068] Step 2: The cleaned substrate is made into the shape of a sensing probe, and a sensing area and a wire area are divided thereon.

[0069] Step 3: Evaporate a gate line in the middle of the substrate, and evaporating 3 source lines parallel to the gate line at equal intervals on both sides of the gate line on the substrate, so that the gate line and the 6 source lines all cross the sensing area and the wire area. The gate line is 3nm thick chromium, 150nm thick gold and 150nm thick silver, and the width is 200μm; each source line includes 3nm thick chromium and 150nm thick gold, and the width of each source line is 5μm.

[0070] Step 4: The substrate treated in step 3 is subjected to UV-ozone cleaning for 10 minutes.

[0071] Step 5: Spin coating a semiconductor layer with cross-linking function above one end of each source line located in the sensing area. The specific process is: control the humidity below 10%, the spin coating speed is 3000rpm, and the spin coating time is 10s; photolithography uses 365nm ultraviolet light to expose the semiconductor film to make it have cross-linking function, and wash away the uncross-linked part, so as to form a semiconductor layer on the source line.

[0072] Step 6: Prepare between two adjacent source lines and between the source line and the gate line Figure 5d The drain line is a 150nm thick gold line with a width of 5μm.

[0073] Step 7: Prepare an encapsulation layer by spin coating on the gate line, multiple source lines and multiple drain lines, and use 365nm ultraviolet light for exposure treatment; make the end of the gate line located in the sensing area located in the first square hole, make the semiconductor layer and the intersection area both located in the second square hole, and the side length of the second square hole is: 3µm~230µm.

[0074] Step 8: Spin coating to form a solid electrolyte layer on the packaging layer, exposing the end of the drain line located in the wiring area and the end of the source line located in the wiring area.

[0075] Step 9: Make an ion selective layer by drop coating on top of the solid electrolyte layer.

[0076] Step 10: Preparation Figure 6 The driving measurement circuit shown connects one end of the gate line located in the conductor area, one end of each source line located in the conductor area, and one end of the rear section of each drain line located in the conductor area to the driving detection circuit.

[0077] At this point, a device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid is prepared. It should be noted that, in this embodiment, the source line, drain line and gate can be prepared by one of evaporation, magnetron sputtering, spraying, inkjet printing, aerosol printing and screen printing. The semiconductor layer, encapsulation layer, solid electrolyte layer and ion selection layer can be prepared by one of spin coating, screen printing, inkjet printing, 3D printing, aerosol printing, electrofluid printing and scraping.

[0078] The prepared sensor device for online real-time monitoring of ions in blood purification waste liquid was used for testing. The test conditions were as follows:

[0079] Under the condition of constant drain voltage (Vd=0.1V), under the forward scan of gate voltage ranging from 0V to +0.8V, the current transfer characteristic curves of a single device in the capture probe array without solid electrolyte layer and ion selection layer, with only ion selection layer, and with both solid electrolyte layer and ion selection layer are plotted, and the transfer characteristic curves are shown in Figure 2. Figure 7 As shown in the figure, it can be seen that under this test condition, the sensor device for online real-time monitoring of ions in blood purification wastewater containing a solid electrolyte layer and an ion selection layer exhibits an excellent current regulation effect. The source current (solid line) can be increased from 10 -9 A to 10 -2 It can be carried out between A.

[0080] For cation detection, under the condition of constant drain voltage (Vd = 0.1 V), the gate-source voltage was scanned from +0.1 V to +0.8 V in the positive direction to capture the transfer characteristics of the output current under the sodium ion selection layer, potassium ion selection layer, and calcium ion selection layer in the probe array, and the transfer characteristic curve was plotted, such as Figure 8 , Fig. 9 , Fig.10 As shown, they are the transfer characteristic curves of sodium ions, potassium ions, and calcium ions at different concentrations. According to the graphical results, it can be seen that under this test condition, the sensor device for online real-time monitoring of ions in blood purification wastewater shows an excellent current regulation effect, and its on-state current increases with the increase of the corresponding ion concentration, and the ion selection layer shows good selectivity, and the current response to non-selective ions is small. Figures 8 to 10 DI represents the transfer characteristic curve in deionized water, which is used as the reference control group, and V G Represents the voltage applied to the gate.

[0081] The performance test of the sensor device for online real-time monitoring of ions in blood purification wastewater was carried out in actual blood purification wastewater. Fig.11a , Fig.11c and Fig.11cThe results of Roche electrolyte analyzer were used as the standard to identify the Na + , K + and Ca 2 + The blood purification wastewater after concentration is further subjected to the Na + , K + and Ca 2+ The concentration was tested and the results showed that the sensor device has a certain detection accuracy. + , K + The results of the test were basically consistent with those of Roche. 2+ The results are within the acceptable error range.

[0082] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A device for real-time monitoring of ion types and ion concentrations in blood purification wastewater, characterized in that: include: Sensing probe and drive detection circuit; The sensing probe includes a sensing region and a wire region; The sensing area is connected to the wire area, the sensing area is located at the head of the sensing probe, and the wire area is located at the middle and rear of the sensing probe; The sensing probe comprises a substrate, on which a gate line and a plurality of source lines are arranged, the gate line and the plurality of source lines both span the sensing area and the wire area, the gate line is located in the middle of the substrate, and the plurality of source lines are located on both sides of the gate line; Each source line is covered with a semiconductor layer above one end of the sensing region; A drain line is arranged between two adjacent source lines and between a source line and a gate line. The drain line is a strip structure and includes a front section and a rear section. The front section is arranged above the semiconductor layer, the front section is perpendicular to the source line and forms a crossing area with the source line, and the rear section is parallel to the source line and crosses the sensing area and the wire area. One end of the gate line located in the conductor area, one end of each source line located in the conductor area, and one end of each drain line located in the conductor area are all connected to the drive detection circuit; The gate line, the plurality of source lines and the plurality of drain lines are covered with an encapsulation layer, the encapsulation layer is provided with a first square hole and a plurality of second square holes, one end of the gate line located in the sensing area is located in the first square hole, the second square hole corresponds to the semiconductor layer one by one, the semiconductor layer and the intersection area are both located in the second square hole, and the side length of the second square hole is: 3µm~230µm; A solid electrolyte layer is disposed above the encapsulation layer, and the solid electrolyte layer covers a plurality of second square holes; The solid electrolyte layer is covered with an ion selective layer.

2. A device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The intersection area is a square, and the side length of the intersection area is 2µm~200µm; the width of the source line is 2µm~200µm; the width of the drain line is 2µm~200µm.

3. The device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The material of the substrate is one of glass, silicon wafer, polyethylene terephthalate PET, polyethylene naphthalate PEN, polydimethylsiloxane PDMS, PMMA, PI, polyurethane PU and polystyrene-ethylene-butylene SEBS.

4. The device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The material of the source line is one of gold, platinum, carbon nanotubes and graphene, the material of the drain line is one of gold, platinum, carbon nanotubes and graphene, and the material of the gate line is one of gold, silver, silver / silver chloride, poly (3,4-ethylenedioxythiophene): polystyrene sulfonate, carbon nanotubes, graphene and graphyne.

5. The device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The material of the semiconductor layer is one of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene], poly(benzimidazole dibenzophenanthroline) and polyethylene glycol (diol) diacrylate; wherein the molecular formula of poly[thiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 28 H 36 O8S4]N, the molecular formula of poly[bithiophene-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene] is [C 26 H 34 O8S3]N, the molecular formula of poly (benzimidazole dibenzophenanthroline) is (C 20 H6N4O2) n , the molecular formula of polyethylene glycol (diol) diacrylate is (C2H4O) n C6H6O3; The thickness of the semiconductor layer is 10nm~200nm; the semiconductor layer is square, and the side length of the semiconductor layer is 3µm~220µm; the width of the source line and the width of the drain line are both smaller than the side length of the semiconductor layer.

6. The device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The material of the encapsulation layer is one of Parylene-C, cellulose, photoresist SU-8, polystyrene, polydimethylsiloxane PDMS and polystyrene-ethylene-butylene SEBS.

7. The device for real-time monitoring of ion types and ion concentrations in blood purification waste liquid according to claim 1, characterized in that: The drive detection circuit is integrated in a chip with a size of 20mm×20mm.

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