CN113616204B - Device capable of being used for CRRT (continuous variable rate) on-line real-time monitoring of dynamic change of blood ionized calcium - Google Patents
Device capable of being used for CRRT (continuous variable rate) on-line real-time monitoring of dynamic change of blood ionized calcium Download PDFInfo
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- CN113616204B CN113616204B CN202010373420.XA CN202010373420A CN113616204B CN 113616204 B CN113616204 B CN 113616204B CN 202010373420 A CN202010373420 A CN 202010373420A CN 113616204 B CN113616204 B CN 113616204B
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- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000011575 calcium Substances 0.000 title claims abstract description 61
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 61
- 239000008280 blood Substances 0.000 title claims abstract description 60
- 210000004369 blood Anatomy 0.000 title claims abstract description 60
- 238000012544 monitoring process Methods 0.000 title claims abstract description 44
- 230000008859 change Effects 0.000 title claims abstract description 27
- 239000007788 liquid Substances 0.000 claims abstract description 95
- 239000012528 membrane Substances 0.000 claims description 42
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 22
- 238000000926 separation method Methods 0.000 claims description 21
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 20
- 239000000463 material Substances 0.000 claims description 19
- 239000000835 fiber Substances 0.000 claims description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- 239000000741 silica gel Substances 0.000 claims description 16
- 229910002027 silica gel Inorganic materials 0.000 claims description 16
- 238000012806 monitoring device Methods 0.000 claims description 13
- 239000001103 potassium chloride Substances 0.000 claims description 10
- 235000011164 potassium chloride Nutrition 0.000 claims description 10
- 229910021607 Silver chloride Inorganic materials 0.000 claims description 9
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims description 9
- 230000005526 G1 to G0 transition Effects 0.000 claims description 8
- 239000000499 gel Substances 0.000 claims description 6
- -1 3-tetramethylbutylphenyl Chemical group 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000001110 calcium chloride Substances 0.000 claims description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 5
- 239000001506 calcium phosphate Substances 0.000 claims description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims description 5
- 150000003017 phosphorus Chemical class 0.000 claims description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 4
- 125000005461 organic phosphorous group Chemical group 0.000 claims 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 abstract description 16
- 229910001424 calcium ion Inorganic materials 0.000 abstract description 16
- 239000012530 fluid Substances 0.000 abstract description 7
- 238000005259 measurement Methods 0.000 abstract description 7
- 230000035484 reaction time Effects 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 34
- 238000001514 detection method Methods 0.000 description 28
- 238000010586 diagram Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 125000006850 spacer group Chemical group 0.000 description 9
- 239000013078 crystal Substances 0.000 description 7
- 230000010100 anticoagulation Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229910001425 magnesium ion Inorganic materials 0.000 description 6
- 229910001414 potassium ion Inorganic materials 0.000 description 6
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000011149 active material Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003014 ion exchange membrane Substances 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
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- 238000003466 welding Methods 0.000 description 3
- 238000010146 3D printing Methods 0.000 description 2
- 238000010989 Bland-Altman Methods 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- QHGRPTNUHWYCEN-UHFFFAOYSA-N dioctyl phenyl phosphate Chemical compound CCCCCCCCOP(=O)(OCCCCCCCC)OC1=CC=CC=C1 QHGRPTNUHWYCEN-UHFFFAOYSA-N 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000003822 epoxy resin Substances 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
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- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 238000007731 hot pressing Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
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- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
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- 238000012959 renal replacement therapy Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3669—Electrical impedance measurement of body fluids; transducers specially adapted therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2230/00—Measuring parameters of the user
- A61M2230/20—Blood composition characteristics
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medical Informatics (AREA)
- Surgery (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Cardiology (AREA)
- Pathology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to the field of medical equipment, in particular to a device for online real-time monitoring of blood ionic calcium dynamic change, which can be used for CRRT. The invention provides a device for monitoring dynamic changes of blood ionic calcium on line in real time, which can be used for CRRT. The device for online real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention can be used for real-time monitoring of ionic calcium concentration in flowing liquid, the electrode can stably work in the fluid, has shorter reaction time, has higher selectivity on calcium ions, has a measurement result which is not influenced by flow velocity and solution PH value, has smaller bias compared with the prior iSTAT blood gas analyzer commonly used in clinic, and can provide online real-time monitoring of blood ionic calcium concentration.
Description
Technical Field
The invention relates to the field of medical equipment, in particular to a device for online real-time monitoring of blood ionic calcium dynamic change, which can be used for CRRT.
Background
Safe and effective anticoagulation is a key and technical difficulty in blood purification, and is particularly prominent in continuous kidney replacement therapy for a long time. Local citrate anticoagulation (RCA) has been demonstrated to have an effective in vitro anticoagulation which avoids prolonged exposure to heparin in continuous renal replacement therapy. RCA can reduce the incidence of dialysis-related hemorrhage, can also improve the service life of the dialyzer and improve the biocompatibility of the dialyzer. Although RCA has many advantages, there are still many technical limitations and difficulties in the clinical practice and application process, which prevent its popularization. The technical key in RCA practice is how to confirm proper citric acid and calcium infusion rates so that the in vivo and in vitro circulating ionic calcium concentration is maintained within a proper, narrow therapeutic target range. Currently, the most commonly used method for implementing RCA in each unit is the so-called "trial and error method", i.e. the concentration of ionized calcium in the patient's internal and external circulation is maintained within a target range (about 1.1 and 0.3mM/L, respectively) by frequently monitoring (typically every 0.5-2 hours) the concentration of ionized calcium in the patient's internal and external circulation, and adjusting the calcium supplement and citric acid infusion rates in time. The method has huge manpower (at least one experienced nurse and doctor familiar with RCA principle are required to be present for 24 hours) and material resources (at least 2 times of ionized calcium is monitored every hour, each time of 80 yuan or 2000-3000 yuan per day) cost, and special monitoring equipment (iSTAT biochemicals, each time of 10-15 ten thousand yuan) is required, which certainly complicates the CRRT process, increases the economic burden of patients and the burden of medical staff, and limits the wide clinical application of RCA-CRRT.
Ion selective electrodes are currently the most commonly used laboratory method for in vitro detection of ionic calcium. The principle is a potential analysis method, which consists of a working electrode, a reference electrode, a temperature electrode and a signal output device. The method can sensitively and specifically respond to the change of the concentration of the ionized calcium in the liquid, and calculate the concentration of the ions according to a Nernst equation.
The traditional structural electrode currently exists: activating for 2-4 days; zero point inconsistency and each electrode need to be calibrated; the temperature affects the active film unevenly, resulting in a disadvantage of non-uniform temperature compensation curve. To realize the non-activation, non-calibration, rapid installation, batch production, safe and reliable monitoring of dynamic blood ionized calcium, the prior art lacks, and cannot realize real-time on-line monitoring of blood samples, thereby limiting the clinical application of the blood sample monitoring device.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, an object of the present invention is to provide a device for online real-time monitoring of blood ionized calcium dynamic changes, which can be used for CRRT, so as to solve the problems in the prior art.
To achieve the above and other related objects, in one aspect, the present invention provides a device for online real-time monitoring of dynamic changes of calcium ions in blood, which can be used for CRRT, comprising an electrode body, wherein a liquid channel, a working electrode cavity, a reference electrode cavity and a temperature electrode cavity are provided on the electrode body;
the working electrode inner cavity extends to the liquid channel, a membrane electrode is arranged between the working electrode inner cavity and the liquid channel, and working electrode inner liquid and a working electrode are arranged in the working electrode inner cavity;
The reference electrode inner cavity comprises a first electrode inner cavity and a second electrode inner cavity, a first separation membrane is arranged between the first electrode inner cavity and the second electrode inner cavity, the second electrode inner cavity extends to the liquid channel, a second separation membrane is arranged between the second electrode inner cavity and the liquid channel, a reference electrode stationary phase and a reference electrode are arranged in the first electrode inner cavity, reference electrode inner liquid and a microporous fiber rod are arranged in the second electrode inner cavity, and the microporous fiber rod extends to the first electrode inner cavity;
The temperature electrode inner cavity extends to the liquid channel, a heat conducting film is arranged between the temperature electrode inner cavity and the liquid channel, and a temperature monitoring device is further arranged in the temperature electrode inner cavity.
In some embodiments of the invention, the liquid channel extends straight, and the diameter of the cross section of the liquid channel is 4.5-5.5 mm.
In some embodiments of the invention, the membrane electrode comprises a first spacer, an active membrane and a second spacer, which are stacked in sequence, the first spacer being located on one side of the liquid channel and the second spacer being located on one side of the working electrode lumen.
In some embodiments of the invention, the material of the first and/or second spacers is silica gel, the active film comprises an active substance, preferably the active substance is selected from organic phosphorus salts, more preferably the organic phosphorus salts are selected from bis [4- (1, 3-tetramethylbutylphenyl) calcium phosphate, the thickness of the first spacer is 0.27 to 0.33mm, the thickness of the active film is 0.27 to 0.33mm, and the thickness of the second spacer is 0.27 to 0.33mm.
In some embodiments of the invention, the working electrode internal fluid is selected from an aqueous solution of calcium chloride and the working electrode is selected from Ag/AgCl wire.
In some embodiments of the invention, the working electrode lumen has a volume of 4.5 to 5.5ml, the working electrode lumen is cylindrical, preferably cylindrical, and the diameter of the lumen cross section is 7.2 to 8.8mm.
In some embodiments of the invention, the material of the first and/or second separation membrane is selected from silica gel, and the thickness of the first and/or second separation membrane is 3.6-4.4 mm.
In some embodiments of the invention, the stationary phase of the reference electrode is selected from potassium chloride gel, the internal solution of the reference electrode is selected from potassium chloride aqueous solution, the length of the microporous fiber rod is 9.5-10.5 mm, the diameter of the cross section is 0.85-0.95 mm, the pore diameter is 0.28-0.32 mm, and the reference electrode is selected from Ag/AgCl wire.
In some embodiments of the invention, the volume of the first electrode lumen is 4.5-5.5 ml, the first electrode lumen is cylindrical, preferably cylindrical, and the diameter of the cavity cross section is 7.2-8.8 mm.
In some embodiments of the invention, the volume of the second electrode lumen is 4.5-5.5 ml, the second electrode lumen is cylindrical, preferably cylindrical, and the diameter of the cavity cross section is 7.2-8.8 mm.
In some embodiments of the invention, the material of the thermally conductive film is selected from thermally conductive silica gel.
In some embodiments of the invention, the temperature monitoring device is selected from thermistors.
In some embodiments of the invention, the volume of the temperature electrode inner cavity is 48-58 mm 2, the temperature electrode inner cavity is cylindrical, preferably cylindrical, and the diameter of the cross section of the cavity is 2.8-3.4 mm.
In some embodiments of the invention, the device further comprises a connector and a wire, wherein the wire is respectively electrically connected with the working electrode, the reference electrode and the temperature monitoring device, and the connector is positioned at two ends of the liquid channel.
In some embodiments of the present invention, the signal output device further comprises a signal acquisition circuit, an amplifying circuit and a display device, which are sequentially connected, and the signal output device is electrically connected with the wire.
The invention further provides a CRRT device, which comprises a CRRT device body, wherein the arterial end and/or the venous end of a CRRT loop of the CRRT device body are connected with the device for monitoring the dynamic change of blood ionic calcium on line in real time.
Drawings
FIG. 1 is a schematic diagram showing the whole apparatus for on-line real-time monitoring of blood ionic calcium dynamic change, which can be used for CRRT in the present invention.
Fig. 2 is a schematic structural diagram of an apparatus for on-line real-time monitoring of blood ionized calcium dynamic changes, which can be used for CRRT in the present invention.
Fig. 3 is a schematic diagram of an electrical signal transmission line according to an embodiment of the invention.
FIG. 4 is a schematic diagram of an in vitro simulated circulation in an embodiment of the invention.
FIG. 5 is a schematic diagram showing a standard curve of crystal liquid detection in an embodiment of the invention.
FIG. 6 is a schematic diagram showing the reaction time of electrode detection in an embodiment of the invention.
FIG. 7 is a schematic diagram showing the stability of the electrode in the embodiment of the invention.
FIG. 8 is a schematic diagram showing the effect of flow rate change on potential readings in an embodiment of the invention.
FIG. 9 is a schematic diagram showing the effect of pH change on potential readings for a solution in an embodiment of the invention.
FIG. 10 is a graph showing the effect of magnesium and potassium concentration changes on the potential readings for the solution in accordance with the embodiments of the present invention.
FIG. 11 is a schematic diagram showing a standard curve of blood test in an embodiment of the invention.
FIG. 12 is a diagram showing the comparison between the electrode detection results and iSTAT detection results in the embodiment of the present invention.
Fig. 13 is a schematic view showing a partial structure of a CRRT device according to the invention.
Description of element reference numerals
1. Electrode body
2. Liquid channel
3. Working electrode lumen
31. Membrane electrode
32. Working electrode inner liquid
33. Working electrode
4. Reference electrode cavity
41. First electrode lumen
411. Stationary phase of reference electrode
412. Reference electrode
42. A second electrode cavity
421. Reference electrode inner liquid
422. Microporous fiber rod
43. First separation film
44. Second separation membrane
5. Temperature electrode lumen
51. Temperature monitoring device
52. Heat conducting film
6. Conducting wire
Detailed Description
In order to make the objects, technical solutions and advantageous technical effects of the present application more apparent, the present application will be further described in detail with reference to the following examples, and those skilled in the art can easily understand other advantages and effects of the present application from the disclosure of the present specification.
The first aspect of the present invention provides a device for online real-time monitoring of dynamic changes of blood ionized calcium, which can be used for CRRT, as shown in fig. 1 and 2, and may include an electrode body 1, where a liquid channel 2, a working electrode cavity 3, a reference electrode cavity 4 and a temperature electrode cavity 5 are provided on the electrode body 1;
the working electrode cavity 3 extends to the liquid channel 2, a membrane electrode 31 is arranged between the working electrode cavity 3 and the liquid channel 2, and working electrode inner liquid 32 and a working electrode 33 are arranged in the working electrode cavity 3;
The reference electrode inner cavity 4 comprises a first electrode inner cavity 41 and a second electrode inner cavity 42, a first separation membrane 43 is arranged between the first electrode inner cavity 41 and the second electrode inner cavity 42, the second electrode inner cavity 42 extends to the liquid channel 2, a second separation membrane 44 is arranged between the second electrode inner cavity 42 and the liquid channel 2, a reference electrode stationary phase 411 and a reference electrode 412 are arranged in the first electrode inner cavity 41, a reference electrode inner liquid 421 and a microporous fiber rod 422 are arranged in the second electrode inner cavity 42, and the microporous fiber rod 422 extends to the first electrode inner cavity 41;
The temperature electrode cavity 5 extends to the liquid channel 2, a heat conducting film 52 is arranged between the temperature electrode cavity 5 and the liquid channel 2, and a temperature monitoring device 51 is also arranged in the temperature electrode cavity 5. The device for online real-time monitoring of blood ionic calcium dynamic change of CRRT provided by the invention can stably work in flowing crystal liquid and blood samples, has shorter reaction time, has higher selectivity for calcium ions, and is free from the influence of flow velocity and solution PH value.
The device for online real-time monitoring of blood ionic calcium dynamic change of CRRT provided by the invention can comprise an electrode body 1, wherein the electrode body 1 can be made of a proper die material generally, so that a proper cavity structure can be formed in the electrode body 1 to accommodate various components in the device for online real-time monitoring of blood ionic calcium dynamic change of CRRT. For example, the material of the electrode body 1 may be a 3D printing material or the like, and specifically may be a photosensitive resin or the like.
In the device for online real-time monitoring of dynamic changes of blood ionized calcium provided by the invention, which can be used for CRRT, a liquid channel 2 can be arranged on the electrode body 1, and the liquid channel 2 is usually used for flowing through liquid to be detected. The shape and size of the liquid channel 2 are generally matched to the flow rate of the liquid to be detected flowing through. For example, in the liquid channel 2, the flow rate of the liquid may be 20ml/min～150ml/min、20ml/min～30ml/min、30ml/min～40ml/min、40ml/min～60ml/min、60ml/min～80ml/min、80ml/min～100ml/min、100ml/min～120ml/min、 or 120ml/min to 150ml/min; for another example, the cross-section of the liquid channel 2 may have a diameter of 4.5-5.5 mm, 4.5-4.8 mm, 4.8-5.2 mm, or 5.2-5.5 mm. The direction of extension of the liquid channel 2 in the electrode body 1 can be adapted to the person skilled in the art, for example, the liquid channel 2 can extend generally straight.
In the device for online real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention, the electrode body 1 can be provided with a working electrode inner cavity 3, and the working electrode inner cavity 3 is usually used for accommodating various parts of a working electrode. The working electrode cavity 3 may extend to the liquid channel 2, and a membrane electrode 31 may be disposed between the working electrode cavity 3 and the liquid channel 2, so that the working electrode and the liquid to be detected in the liquid channel 2 may form a suitable contact. The shape and size of the working electrode lumen 3 should be adjustable to those skilled in the art, for example, the volume of the working electrode lumen 3 may be 4.5 to 5.5ml, 4.5 to 4.8ml, 4.8 to 5.2ml, or 5.2 to 5.5ml, and the working electrode lumen 3 may be cylindrical, preferably may be cylindrical, and the diameter of the lumen cross section may be 7.2 to 8.8mm, 7.2 to 7.5mm, 7.5 to 7.8mm, 7.8 to 8.2mm, 8.2 to 8.5mm, or 8.5 to 8.8mm.
In the present application, in the working electrode cavity 3, the membrane electrode 31 includes a first spacer, an active membrane, and a second spacer that are sequentially stacked. The first gasket is positioned on one side of the liquid channel 2 and can be contacted with liquid to be detected, so as to strengthen the active membrane and reduce the impact force of the active membrane on the fluid. Suitable types and sizes of gasket materials suitable for use in the working electrode should be known to those skilled in the art, for example, the material of the first gasket may typically be silica gel or the like, and for further example, the thickness of the first gasket may be 0.27 to 0.33mm, 0.27 to 0.29mm, 0.29 to 0.31mm, or 0.31 to 0.33mm. The second gasket is located on one side of the working electrode lumen 3 and can be in contact with the working electrode internal fluid 32 for closing the electrode lumen. Suitable gasket materials types and sizes for the working electrode should be known to those skilled in the art, for example, the material of the second gasket may typically be silica gel or the like, and for further example, the thickness of the second gasket may be 0.27 to 0.33mm, 0.27 to 0.29mm, 0.29 to 0.31mm, or 0.31 to 0.33mm. The active membrane is typically positioned between the first and second gaskets for sensing the concentration of ionic calcium in the fluid, the active membrane is typically selectively responsive to calcium ions, and the relationship between the potential of the active membrane and the content of calcium ions should be capable of meeting the nernst formula. Suitable active membrane types should be known to those skilled in the art, and for example, the active membrane may generally include calcium ion active materials (e.g., alkylphenyl calcium phosphate, etc.), and may also include plasticizers (e.g., dioctyl phenylphosphate, etc.), high molecular weight polymers (e.g., PVC, etc.), and the like. The thickness of the active film may be 0.27 to 0.33mm, 0.27 to 0.29mm, 0.29 to 0.31mm, or 0.31 to 0.33mm. The active substance can generally react specifically with calcium ions. Suitable active materials for the active film of the working electrode should be known to those skilled in the art, for example, the active material may be an organic phosphorus salt or the like, and for example, the organic phosphorus salt may be bis [4- (1, 3-tetramethylbutylphenyl) calcium phosphate or the like.
In the application, the working electrode inner cavity 3 can be provided with a working electrode inner liquid 32 and a working electrode 33, and the working electrode 33 mainly has the function of converting an ion signal into an electric signal for transmission, so that the liquid to be detected in the liquid channel 2 can be detected. Suitable working electrode solutions 32 and 33 suitable for use in working electrodes should be known to those skilled in the art, for example, the working electrode solution 32 may be selected from aqueous calcium chloride solutions, and the concentration of the solution may be 9.5 to 10.5mmol/L, 9.5 to 9.7mmol/L, 9.7 to 9.9mmol/L, 9.9 to 10.1mmol/L, 10.1 to 10.3mmol/L, or 10.3 to 10.5mmol/L; as another example, the working electrode 33 may be made of Ag/AgCl wire, etc., and the length of the Ag/AgCl wire may be 27 to 33mm, 27 to 29mm, 29 to 31mm, or 31 to 33mm, and the diameter may be 0.27 to 0.33mm, 0.27 to 0.29mm, 0.29 to 0.31mm, or 0.31 to 0.33mm. Typically, working electrode 33 may be electrically connected to a suitable lead wire 6 and may extend out of working electrode lumen 3 to transmit the detection signal to a signal output device.
In the device for online real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention, the electrode body 1 can be provided with a reference electrode inner cavity 4, and the reference electrode inner cavity 4 is usually used for accommodating various components of a reference electrode. The reference electrode lumen 4 may include a first electrode lumen 41 and a second electrode lumen 42, and a first separation membrane 43 may be disposed between the first electrode lumen 41 and the second electrode lumen 42, so that the reference electrode lumen 4 may be divided into the first electrode lumen 41 and the second electrode lumen 42. The second electrode cavity 42 may extend to the liquid channel 2, and a second separation membrane 44 is disposed between the second electrode cavity 42 and the liquid channel 2, so that the reference electrode and the liquid to be detected in the liquid channel 2 may form a suitable contact. Suitable materials and dimensions for the separation membrane suitable for the reference electrode should be known to those skilled in the art, for example, the material of the first separation membrane 43 may be selected from silica gel and the like, and the thickness of the first separation membrane 43 may be 3.6 to 4.4mm, 3.6 to 3.9mm, 3.9 to 4.1mm, or 4.1 to 4.4mm; for another example, the material of the second separation film 44 may be selected from silica gel, etc., and the thickness of the second separation film 44 may be 3.6 to 4.4mm, 3.6 to 3.9mm, 3.9 to 4.1mm, or 4.1 to 4.4mm; the shape and size of the reference electrode lumen 4 should be adjustable to those skilled in the art, for example, the volume of the first electrode lumen 41 may be 4.5 to 5.5ml, 4.5 to 4.8ml, 4.8 to 5.2ml, or 5.2 to 5.5ml, the first electrode lumen 41 may be cylindrical, preferably may be cylindrical, the diameter of the lumen cross section may be 7.2 to 8.8mm, 7.2 to 7.5mm, 7.5 to 7.8mm, 7.8 to 8.2mm, 8.2 to 8.5mm, or 8.5 to 8.8mm; for another example, the volume of the second electrode lumen 42 may be 4.5-5.5 ml, 4.5-4.8 ml, 4.8-5.2 ml, or 5.2-5.5 ml, the second electrode lumen 42 may be cylindrical, preferably may be cylindrical, and the diameter of the lumen cross section may be 7.2-8.8 mm, 7.2-7.5 mm, 7.5-7.8 mm, 7.8-8.2 mm, 8.2-8.5 mm, or 8.5-8.8 mm; for another example, the first electrode lumen 41 and the second electrode lumen 42 may have a uniform overall extending direction, so that the reference electrode lumen 4 may be cylindrical in overall, and preferably may be cylindrical.
In the present application, the first electrode cavity 41 is provided with a reference electrode stationary phase 411 and a reference electrode 412, so that the reference electrode potential is stabilized. Suitable reference electrode internal fluids and reference electrodes should be known to those skilled in the art, for example, the reference electrode stationary phase 411 may be selected from potassium chloride gel, etc., wherein the concentration of potassium chloride may be a saturated concentration; for another example, the reference electrode may be selected from Ag/AgCl wires, etc., the size of which may be 27-33 mm, 27-29 mm, 29-31 mm, or 31-33 mm long, and the diameter may be 0.27-0.33 mm, 0.27-0.29 mm, 0.29-0.31 mm, or 0.31-0.33 mm. Typically, the reference electrode may be electrically connected to a suitable lead wire 6 and may extend out of the first electrode lumen 41 to transmit the detection signal to the signal output device.
In the present application, the reference electrode inner liquid 421 and the microporous fiber rod 422 are disposed in the second electrode inner cavity 42, and the microporous fiber rod 422 extends to the first electrode cavity 41, so as to form a stable and continuous electronic circuit. Suitable reference electrode internal solutions and microporous fiber rods suitable for use in reference electrodes should be known to those skilled in the art, for example, the reference electrode internal solution 421 may be selected from potassium chloride aqueous solutions and the like, and the concentration of the solution may be 3.5 to 4.0mmol/L; for another example, the microporous fiber rod may slowly extravasate the potassium chloride solution, and the microporous fiber rod 422 may have a length of 9.5 to 10.5mm, 9.5 to 9.8mm, 9.8 to 10.2mm, or 10.2 to 10.5mm, a cross-sectional diameter of 0.85 to 0.95mm, 0.85 to 0.88mm, 0.88 to 0.92mm, 0.92 to 0.95mm, and a pore size of 0.28 to 0.32mm, 0.28 to 0.29mm, 0.29 to 0.30mm, 0.30 to 0.31mm, or 0.31 to 0.32mm. Typically, the second electrode lumen 42 is in communication with the first electrode lumen 41 through a microporous fiber rod, allowing for sustained slow penetration of the potassium chloride solution.
In the device for online real-time monitoring of dynamic changes of blood ionized calcium provided by the invention and applicable to CRRT, a temperature electrode inner cavity 5 can be arranged on the electrode body 1, and the temperature electrode inner cavity 5 is usually used for detecting each component of the temperature of the liquid to be detected in the liquid channel 2. The temperature electrode cavity 5 may extend to the liquid channel 2, and a heat conducting film 52 is disposed between the temperature electrode cavity 5 and the liquid channel 2, so that the heat conducting film 52 may form a suitable contact with the liquid to be detected in the liquid channel 2, and transfer heat to the temperature monitoring device 51. The shape and size of the temperature electrode lumen 5 should be adjustable to those skilled in the art, for example, the volume of the temperature electrode lumen 5 may be 48 to 58mm 2、48～50mm2、50～52mm2、52～54mm2、54～56mm2, or 56 to 58mm 2, the temperature electrode lumen 5 may be cylindrical, preferably may be cylindrical, and the diameter of the lumen cross section may be 2.8 to 3.4mm, 2.8 to 3.0mm, 3.0 to 3.2mm, or 3.2 to 3.4mm.
In the present application, suitable heat conductive films 52, temperature monitoring devices 51 suitable for detecting the temperature of the liquid to be detected in the liquid channel 2 should be known to those skilled in the art, for example, the material of the heat conductive film 52 may be selected from heat conductive silica gel or the like, and the thickness of the heat conductive film 52 may be 0.27 to 0.33mm, 0.27 to 0.29mm, 0.29 to 0.31mm, or 0.31 to 0.33mm; for another example, the temperature monitoring device 51 may be selected from a thermistor and the like. Typically, the temperature monitoring device 51 may be electrically connected to a suitable lead wire 6, and the lead wire 6 may extend into the temperature electrode lumen 5 to transmit the detection signal to the signal output device.
The device for on-line real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention can be used for on-line real-time monitoring of blood ionic calcium dynamic change for CRRT, and can also comprise a connector as shown in figure 13, wherein the connector can be used for installing the device for on-line real-time monitoring of blood ionic calcium dynamic change for CRRT at a proper working position. The connectors may typically be located at both ends of the liquid channel 2, the kind of connectors being adjustable to a person skilled in the art, for example the connectors may be luer connectors or the like.
The device for online real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention can also comprise a signal output device, wherein the signal output device can generally comprise a signal acquisition circuit, an amplifying circuit, a display device and the like which are sequentially connected, and the signal output device can generally be electrically connected with a wire 6, so that data can be collected through the signal acquisition circuit and transmitted to the display device through the amplifying circuit. Suitable signal collectors, amplification circuits, display devices should be known to those skilled in the art, for example, the display device may be a display or the like.
The second aspect of the invention provides a CRRT device, comprising a CRRT device body, wherein the arterial end and/or the venous end of a CRRT loop of the CRRT device body are connected with the device for online real-time monitoring of dynamic changes of blood ionic calcium for CRRT. On the CRRT device, the liquid to be tested is typically a blood sample. After the concentration of the ionized calcium is measured by the device, the acquired signals can be output, and the readings can be displayed through an output device. After the device is used for continuous kidney substitution treatment by RCA anticoagulation, the technical difficulty of RCA implementation can be obviously reduced, and the anticoagulation mode is easier to popularize, so that clinical benefit is brought to more hemodialysis patients.
The device for online real-time monitoring of blood ionic calcium dynamic change for CRRT provided by the invention can monitor the ionic calcium concentration in flowing liquid (crystal liquid and blood) in real time, the electrode can stably work in the fluid, has shorter reaction time, has higher selectivity on calcium ions, has a measuring result which is not influenced by the flow rate and the PH value of the solution, has smaller bias compared with the iSTAT blood gas analyzer commonly used in clinic at present, and can provide online real-time monitoring of the blood ionic calcium concentration. In addition, the device has the characteristics of non-activation, non-calibration, quick installation, mass production, safety, reliability and the like, and has good industrialization prospect.
The application is further illustrated by the following examples, which are not intended to limit the scope of the application.
Example 1
(1) Calcium ion exchange membrane composition and thermal processing:
calcium ion exchange membrane composition: contains 15mg of bis [4- (1, 3-tetramethylbutylphenyl) calcium phosphate, 400mg of dioctyl phenyl phosphate, 170mgPVC. The film thickness was 0.3mm.
And (3) hot working: the calcium ion exchange membrane is protected and clamped in the middle by a PP film material, and is placed in a hot roller press, the temperature is kept at 75 ℃,
Hot-pressing for eight times to make the film thickness uniform and ensure that the active ingredients are uniformly distributed in the PVC plastic. (this process facilitates the uniformity of the calculation curve and the quantitative production)
(2) Calcium ion sensor:
The electrode mold is made by applying a 3D printing technology, the printing material is photosensitive resin, and the printing appearance is shown in figure 1. The electrode die comprises a cuboid with the size of 50mm 15mm 45mm, a straight line extending sample through hole is formed in the length direction, a 1# hole, a 2# hole and a 3# hole are formed in one side face of a cuboid body with the aperture of 4.85mm, the apertures are 8.3mm, 8.3mm and 3.2mm respectively, the intervals among the holes are 3mm, the holes extend to the through hole and are communicated, and the extending direction is perpendicular to the extending direction of the through hole.
Working electrode: and (3) adding a gasket with the thickness of 0.3mm and an active membrane into the 1# hole in sequence, extending the three-layer structure to the bottom of the 1# hole, wherein the diameters of the sections of the gasket and the active membrane are basically the same as the diameter of the 1# hole, and fixing the membrane pressing structure by using an M8 threaded piece with the length of 10 mm. 1ml polyurethane solid gel containing 0.01M CaCl2 and 0.1M sodium chloride, 0.3mm silver/silver chloride wire is added into the cavity, the cavity is sealed by a silica gel pad, epoxy resin is added for encapsulation, and red tetrafluoro lead is led out (in welding and wiring terminals)
A reference electrode: sequentially adding 8.1mm silica gel plugs (diameter 8.1mm, thickness 3mm, center penetrating 0.9mm microporous fiber rods), saturated potassium chloride solid gel, 8.1mm silica gel plugs (diameter 8.1mm, thickness 3mm, center penetrating 0.9mm microporous fiber rods), saturated potassium chloride gel solution, 0.3mm silver/silver chloride wires, sealing with silica gel pads, adding epoxy resin for encapsulation, and leading out yellow tetrafluoro leads (in welding and wiring terminals);
Temperature electrode: in the 3# hole, NTC thermistor is placed in 316L medical stainless steel shell and sealed by heat-conducting silica gel, and the tetrafluoro black wire (in the welding and wiring terminal) is led out
The two ends are glued with a luer connector by using UV glue to obtain the complete electrode, and the luer connector and the continuous kidney substitution treatment pipeline have good universality. (the sensor structure is beneficial to the uniformity and quantitative production of calculation curves)
(3) And (3) data display:
The electrode adopts an external instrument to receive signals, and can display potential signals or calcium ion concentration. Meanwhile, the instrument band has a simple programming function, and automatic multi-section curve compensation and correction can be realized by inputting the slope and intercept of a standard curve and a temperature value. See fig. 3 for a schematic circuit transfer diagram.
Example 2
Electrode detection
(1) In vitro simulated circulation establishment
The in vitro simulated closed cycle was constructed using a small peristaltic pump, PVC hose, beaker, three-way valve, etc. (schematic view see fig. 4). The beaker is filled with liquid to be measured, and the liquid to be measured can comprise crystal liquid, blood and the like. The crystal liquid is calcium chloride solution, and the preparation method comprises the following steps: according to the concentration requirement, adding 10% calcium chloride solution with different volumes into 0.15mmol/L sodium chloride solution to obtain calcium chloride solution with different concentrations, wherein the concentration range of calcium ions is 0.01-3.00mmo/L so as to meet the clinical detection requirement. The blood is whole blood from domestic pigs, common heparin is added in advance for full anticoagulation, the concentration is 5000IU/100ml whole blood, and a calcium chloride solution is added according to the experimental requirement to regulate the concentration of ionic calcium.
(2) Electrode detection flow
The electrodes were allowed to stand overnight in 0.1mmol/L calcium chloride solution before detection. After the in vitro simulation closed circulation is constructed, a small peristaltic pump is started to enable liquid to fill the pipeline, and whether bubbles are generated in the pipeline is observed. The electrodes are equipped with an external display screen, which can display potential readings or ion concentrations (input slope, automatic conversion after intercept). Due to the large influence of temperature on the electric potential, detection is performed at room temperature and the fluctuation of the room temperature is controlled to be less than 0.5 ℃. Data analysis was performed using SPSS 20.0 and medcalc13.5 statistical software. The continuous variable is described by means of mean value and standard deviation, the standard curve is calculated by means of linear regression, and the statistical methods are realized by means of SPSS software. The Relative Standard Deviation (RSD) is equal to the standard deviation of multiple measurements of the same sample divided by the measurement average to describe the accuracy of the electrode measurements.
When the electrode is used for detecting the crystal liquid, a standard curve is established by taking the logarithm of the concentration as an abscissa and the potential reading as an ordinate according to the known concentration of the ionic calcium in the solution. The specific results of the electrode detection in the crystal liquid are shown in fig. 5, when the calcium ion concentration fluctuates between 0.01 and 3.00mmol/L, the electric potential and the ionic calcium concentration shown by the electrode satisfy the nernst reaction, namely the logarithm of the electric potential and the ionic calcium concentration satisfy the linear relation (R 2 =0.9970), and a standard curve is established according to the specific results. When the concentration of the ionized calcium changes, the potential reading of the electrode starts to change after 1-2 seconds, and the reading is stabilized for about 5-6 seconds, as shown in fig. 6, so that the electrode has shorter reaction time and can be monitored in real time.
In addition, some tests were performed on the characteristics of the electrodes to examine the effect of the effective operating time, reaction time, and liquid flow rate, solution PH, magnesium and potassium ion concentration changes on the potential readings.
When the effective working time of the detection electrode is long, a calcium chloride solution with lower concentration (0.1 mmol/L) and a calcium chloride solution with higher concentration (1 mmol/L) are taken as liquids to be detected respectively, potential readings are recorded every 15 minutes, and the relative standard deviation between recorded values is calculated after 6 hours of recording so as to analyze the stability of electrode detection. The results of the effective operation time period detection of the electrode are shown in FIG. 7 and Table 1, and the electrode can stably operate in a lower concentration calcium chloride solution (0.1 mmol/L) or a higher concentration calcium chloride solution (1.0 mmol/L) for at least 6 hours, and the relative standard deviation between the records is 0.29% (0.1 mmol/L) or 0.24% (1.0 mmol/L solution).
Table 1 differences recorded at different time points
| Calcium chloride solutions of different concentrations | 0.1mmol/L | 1mmol/L |
| Relative standard deviation of each record | 0.29％ | 0.24％ |
When the influence of the flow rate on the potential reading is detected, 0.1mmol/L calcium chloride solution is used as the liquid to be detected, the flow rate is gradually increased to 110ml/min every time from 50ml/min, the reading is recorded, and the experiment is repeated three times. Effect of flow rate on potential readings the detection results are shown in fig. 8 in particular, with the potential readings being hardly affected by the flow rate change and the measurement results not affected by the flow rate value when the flow rate is gradually increased from 50ml/min to 110 ml/min.
When the influence of the pH value of the solution on the potential reading is detected, 0.1mmol/L and 1mmol/L of calcium chloride solution are taken as the liquid to be detected, concentrated hydrochloric acid or 1mol/L of sodium hydroxide solution is respectively added to adjust the pH value of the solution, and the potential reading when the pH of the solution fluctuates between 5 and 10 is recorded. The effect of the change in solution pH on the potential readings is shown in particular in fig. 9, where the change in pH has no significant effect on the electrode readings when the solution pH is in the range of 5-10, and the measurement is not affected by the solution pH.
When the influence of the magnesium ion concentration and the potassium ion concentration on the potential reading is detected, 1mol/L magnesium chloride solution and 3.5mol/L potassium chloride solution which are prepared in advance are taken as liquid to be detected, 0.1mmol/L calcium chloride solution is added to adjust the magnesium ion concentration and the potassium ion concentration, the magnesium ion concentration range is 0-1.25mmol/L, the potassium ion concentration range is 0-7mmol/L, and the potential reading is recorded. The effect of the change in the concentration of magnesium ions and potassium ions on the electrode readings is shown in fig. 10, and it can be seen that the addition of either magnesium ions or potassium ions to the calcium chloride solution does not significantly affect the potential readings, indicating that the electrode has a higher selectivity for calcium ions.
After testing the electrode characteristics, selecting a calcium chloride solution with known concentration as the liquid to be tested to detect in an in-vitro simulation cycle, repeatedly detecting the same concentration solution for 5 times, wherein each detection is separated by 5 minutes, comparing the electrode reading with the known concentration, and calculating the accuracy and precision of the electrode result and the known concentration ratio and the relative standard difference analysis electrode of the detection result. The specific results are shown in Table 2. As can be seen from table 2, when the solution concentration is low, the relative error between the measurements is large, and as the solution concentration increases, the relative error gradually decreases; the deviation of the measured result from the actual concentration is not more than 5%.
TABLE 2 continuous detection results of different concentration solution electrodes
Electrodes for blood testing, the concentration of ionized calcium in whole blood was measured using iSTAT blood gas analyzer (available from yaban corporation) and a standard curve was established based on the logarithm of the ion concentration and the corresponding potential reading, the results are shown in fig. 11. The electrode potential satisfies the same linear relationship as the blood ionic calcium concentration (R 2 =0.9994), with a slope of 20.91±0.26mV. Then, electrodes are used for detecting ionic calcium with different concentrations in blood, 10% (w/v) calcium chloride solution (0.9 mol/L) is continuously added in whole blood to adjust the concentration of the ionic calcium, the obtained liquid is used as liquid to be detected in an in-vitro simulation cycle, electrode readings are recorded, medCalc software is used and a Bland-altman method is adopted to compare with the detection result of a iSTAT blood gas analyzer, iSTAT detection results are used as horizontal coordinates, the percentage of (iSTAT results-electrode results)/iSTAT results are used as vertical coordinates to draw a graph, and the deviation degree of electrode detection and iSTAT results is analyzed. The results are shown in FIG. 12. Linear regression shows that the electrode detection results are significantly linearly related to iSTAT detection results (R 2 =0.999); bland-altman analysis showed that the average bias of the electrode results and iSTAT results was 0.9%, the maximum bias was 4.7%, and the 95% consistency limit was (-3.2%, 5.1%), indicating that the electrode detection results and iSTAT detection results were less than 10% biased, which is a clinically acceptable error. Therefore, the electrode can accurately detect the concentration of ionized calcium in flowing blood, and compared with the existing clinically common method for detecting ionized calcium, the electrode has smaller deviation.
In summary, the present invention effectively overcomes the disadvantages of the prior art and has high industrial utility value.
The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (12)
1. The device for online real-time monitoring of blood ionic calcium dynamic change for CRRT is characterized by comprising an electrode body (1), wherein a liquid channel (2), a working electrode inner cavity (3), a reference electrode inner cavity (4) and a temperature electrode inner cavity (5) are arranged on the electrode body (1);
The working electrode inner cavity (3) extends to the liquid channel (2), a membrane electrode (31) is arranged between the working electrode inner cavity (3) and the liquid channel (2), and working electrode inner liquid (32) and a working electrode (33) are arranged in the working electrode inner cavity (3);
The reference electrode inner cavity (4) comprises a first electrode inner cavity (41) and a second electrode inner cavity (42), a first separation membrane (43) is arranged between the first electrode inner cavity (41) and the second electrode inner cavity (42), the second electrode inner cavity (42) extends to the liquid channel (2), a second separation membrane (44) is arranged between the second electrode inner cavity (42) and the liquid channel (2), a reference electrode stationary phase (411) and a reference electrode (412) are arranged in the first electrode inner cavity (41), a reference electrode inner liquid (421) and a microporous fiber rod (422) are arranged in the second electrode inner cavity (42), and the microporous fiber rod (422) extends to the first electrode inner cavity (41);
The temperature electrode inner cavity (5) extends to the liquid channel (2), a heat conducting film (52) is arranged between the temperature electrode inner cavity (5) and the liquid channel (2), and a temperature monitoring device (51) is further arranged in the temperature electrode inner cavity (5); the liquid channel (2) extends linearly, and the diameter of the cross section of the liquid channel (2) is 4.5-5.5 mm; the membrane electrode (31) comprises a first gasket, an active membrane and a second gasket which are sequentially overlapped, wherein the first gasket is positioned on one side of the liquid channel (2), and the second gasket is positioned on one side of the inner cavity (3) of the working electrode.
2. The device for on-line real-time monitoring of blood ionic calcium dynamic changes according to claim 1, wherein the first pad and/or the second pad are/is made of silica gel, the active membrane comprises an active substance, the active substance is selected from organic phosphorus salts, the thickness of the first pad is 0.27-0.33 mm, the thickness of the active membrane is 0.27-0.33 mm, and the thickness of the second pad is 0.27-0.33 mm.
3. The apparatus for on-line real-time monitoring of blood ionic calcium dynamic changes according to claim 2, wherein said organic phosphorous salt is selected from the group consisting of bis [4- (1, 3-tetramethylbutylphenyl) calcium phosphate.
4. The device for on-line real-time monitoring of blood ionic calcium dynamic changes available for CRRT according to claim 1, wherein said working electrode inner liquid (32) is selected from calcium chloride aqueous solution and said working electrode is selected from Ag/AgCl wire;
and/or the volume of the working electrode inner cavity (3) is 4.5-5.5 ml, the working electrode inner cavity (3) is cylindrical, and the diameter of the cross section of the cavity is 7.2-8.8 mm.
5. The device for on-line real-time monitoring of blood ionic calcium dynamic changes according to claim 4, wherein the working electrode lumen (3) is cylindrical.
6. The device for online real-time monitoring of blood ionized calcium dynamic changes for CRRT according to claim 1, wherein the material of the first separation membrane (43) and/or the second separation membrane (44) is selected from silica gel, and the thickness of the first separation membrane (43) and/or the second separation membrane (44) is 3.6-4.4 mm;
And/or the reference electrode stationary phase (411) is selected from potassium chloride gel, the reference electrode internal liquid (421) is selected from potassium chloride aqueous solution, the length of the microporous fiber rod is 9.5-10.5 mm, the diameter of the cross section is 0.85-0.95 mm, the aperture is 0.28-0.32 mm, and the reference electrode is selected from Ag/AgCl wire;
and/or the volume of the first electrode inner cavity (41) is 4.5-5.5 ml, the first electrode inner cavity (41) is cylindrical, and the diameter of the cross section of the cavity is 7.2-8.8 mm;
and/or the volume of the second electrode inner cavity (42) is 4.5-5.5 ml, the second electrode inner cavity (42) is cylindrical, and the diameter of the cross section of the cavity is 7.2-8.8 mm.
7. The device for on-line real-time monitoring of blood ionized calcium dynamic changes available for CRRT according to claim 6, wherein said first electrode lumen (41) is cylindrical; and/or, the second electrode lumen (42) is cylindrical.
8. The device for on-line real-time monitoring of blood ionized calcium dynamic changes available for CRRT according to claim 1, wherein the material of said heat conducting membrane (52) is selected from heat conducting silica gel;
And/or the temperature monitoring device (51) is selected from thermistors;
And/or the volume of the temperature electrode inner cavity (5) is 48-58 mm 2, the temperature electrode inner cavity (5) is cylindrical, and the diameter of the cross section of the cavity is 2.8-3.4 mm.
9. The device for on-line real-time monitoring of blood ionized calcium dynamic changes available for CRRT according to claim 8, wherein the temperature electrode lumen (5) is cylindrical.
10. The device for on-line real-time monitoring of blood ionized calcium dynamic changes available for CRRT according to claim 1, further comprising a connector and a wire (6), wherein the wire (6) is electrically connected with the working electrode (33), the reference electrode (412) and the temperature monitoring device (51), respectively, and the connector is located at two ends of the liquid channel (2).
11. The apparatus for on-line real-time monitoring of blood ionized calcium dynamic changes available for CRRT according to claim 10, further comprising a signal output device, wherein the signal output device comprises a signal collecting circuit, an amplifying circuit and a display device, which are sequentially connected, and the signal output device is electrically connected with the wire (6).
12. A CRRT device, characterized in that the CRRT device comprises a CRRT device body, and an arterial end and/or a venous end of a CRRT loop of the CRRT device body is connected with the device for on-line real-time monitoring of blood ionic calcium dynamic change for CRRT according to any one of claims 1-11.
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