WO2022238754A1 - System and method for monitoring levels of free electrolytes in biological fluids - Google Patents
System and method for monitoring levels of free electrolytes in biological fluids Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3577—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N2021/0106—General arrangement of respective parts
- G01N2021/0118—Apparatus with remote processing
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- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
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- Investigating Or Analysing Biological Materials (AREA)
- Fuel Cell (AREA)
Abstract
A System (100) for monitoring levels of free electrolytes in biological fluids, able to monitor the concentration of at least one free electrolyte in at least one biological sample of at least one user, comprising: a NIR spectrometer (102); a support (101), able to acquire one or more biological fluid samples; at least one data processing block (103); at least one data management block (111); at least one physical or logical interfacing device (104); a sorting center (110). Said support (101) being treated with a chelating compound, said chelating compound being specific for the free electrolyte to be detected.
Description
DESCRIPTION
"System and method for monitoring levels of free electrolytes in biological fluids" The present invention is related to a system for monitoring levels of free electrolytes in biological fluids.
The present invention is, moreover, related to a method for monitoring levels of free electrolytes in biological fluids. In particular, as an example of non-limiting application, the present invention is related to a system and to a method of monitoring levels of free calcium in blood samples, for remote monitoring of calcemia.
As it is known, because of the crucial role in several cellular operations, the concentration of several ions in LEC must be kept within a strict range. Ions of clinic relevance in medicine are: Sodium, Potassium, Chlorine, Calcium,
Phosphorus. Among free ionic forms, divalent ions are particularly relevant and particularly difficult to detect because of their instability.
For example, Zinc ion has clinical relevance for Wilson disease, Lithium ion in pharmacology, Lithium salts being
1
useful for the treatment of several psychiatric diseases their monitoring is important to prevent passing toxicity thresholds, Magnesium ion is moreover a cofactor in several enzymes, and lastly for example the monitoring of lead ion is relevant for poisoning cases.
Among free divalent ions, which monitoring in biological fluids constitute object of the present patent, as an indicative but not exclusive example and for clarity of the presentation, hereafter will be presented the state of the art related to Calcium ion.
Calcium is an ion mainly extracellular, that is located for almost 99% in the skeleton, which is a kind of reserve to maintain the normal concentration in the extracellular liquid (LEC). Many cellular processes depend on Calcium, like for example enzymatic reactions, membrane transport, nervous transmission, muscular and cardiac, platelet aggregation. Calcium is essential, moreover, for making hard tissues (bones and teeth) and neuromuscular operations. Calcium is comprised in the plasma in three forms: 50% is ionic or free, the only metabolically active; the remaining part develops ionic bonds with proteins (mainly with albumin and less with globulines; this form is about 40% of total Calcium) or labile complexes
2
with phosphate ions, citrate, lactate and bicarbonate (chelated form, which represents about 10% of total Calcium).
Because of the essential role in several cellular operations, concentration of ionic Calcium in LEC must be maintained within a strict range. In normal conditions, this concentration is controlled regulating the speed of passage of Calcium through intestinal and renal epithelium. This regulation is realized mainly by modulation of hematic levels of hormones Parathormone (PTH), 1,25 di-hidroxy-Vitamin D and Calcitonin.
There are several diseases caused by an altered equilibrium of Calcium/Phosphorus and that require a constant monitoring of levels of calcemia (hypo- and hyper-calcemic syndromes). The measurement of the levels of Calcium is moreover done systematically after every total thyroidectomy operation. During the post-operation, indeed, there would be a temporary and/or chronic reduction of levels of Calcium that requires a strict control of calcemia during the weeks after the operation for a potential therapeutic treatment. The regularity of monitoring of serum levels of Calcium is highly related to the stability of calcemia of the patient. Some patients require a control of Calcium every 3-6 months, while
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unstable patients could require a control of Calcium every week or every day. Moreover, every time is required a modification of the therapy, it is necessary to perform a control of hematic Calcium to verify its suitability. The pathological condition that exemplifies the require of a strict monitoring of hematic levels of calcemia and phosphorus is Hypoparathyroidism. This clinical condition is characterized by the inability of the organism to maintain suitable levels of calcemia caused by deficiency or failure of Parathormone (PTH). Patients afflicted with this disease must take supplements comprising Calcium salts and active Vitamin D, to stabilize calcium levels in the blood. The significant reduction of hematic levels of Calcium is linked to several symptomatology, which seriousness depend on the concentration of Calcium and the speed with which arises hypocalcemia. Most common symptomatology comprise:tingling in the extremities and peri buccal level, cramps and paraesthesia, fatigue, tiredness, depression, psychomotor slowdown up to convulsions and altered heart rhythm which can even be fatal. Therefore, from a point of view hypocalcemia is a medical urgency, from another point of view hypocalcemia causes a daily worse of life of patients. The non-optimal control of calcemia
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and high variations of electrolytes seem to highly contribute to cause the reduction of physical and emotional of patients afflicted by this condition. International guidelines recommend to maintain calcemia in the low limit, to reduce the risk of complications related to the use of high doses of supplements of Calcium and Vitamin D.
However, this could cause a greater risk of hypocalcemia.
Symptoms of high and low therapeutic doses are not specific and subjective and require every time a laboratory confirm by a venous blood sample to control calcemia.
It is therefore evident that the management of most of disorders related to Calcium/Phosphorus is not suitable because of the lack of a specific system able to allow the monitoring of the specific therapy at own home. Moreover are already known scientific studies on the measurement of free ionic Calcium by near-infrared spectroscopy (NIR), which however are related to applications in agronomic and food industries, and all known methods are based on specific pretreatment of samples and extraction procedures that cannot be replicated on human blood.
Scope of the present invention is to provide a system for monitoring levels of free electrolytes in human biological
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matrixes, in particular divalent ionic forms, as non-limiting example levels of free Calcium in blood samples, that allows to perform the house monitoring of said free electrolytes and, for example, of calcemia and then modify, basing on detected values, the dosage of the established therapy, so to go beyond limits of known systems and methods for the measurement of calcemia.
According to the present invention, it is realized a system for monitoring levels of free electrolytes in biological fluids, as defined in claim 1.
According to the present invention, it is realized a method for monitoring levels of free electrolytes in biological fluids, as defined in claim 10.
For a better understanding of the present invention, it is described hereafter a preferred embodiment, as a non limiting example, with reference to the attached drawings, wherein: figure 1 shows a schematic diagram of a system for monitoring levels of free electrolytes in biological fluids, according to the invention;
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- figure 2 shows a scheme of a portion of the system for monitoring levels of free electrolytes in biological fluids, according to the invention.
Regarding said figures, and in particular figure 1, a system 100 for monitoring levels of free electrolytes in biological fluids is shown, according to the invention.
In detail, the system 100 for monitoring levels of free electrolytes in biological fluids comprises:
- a NIR spectrometer 102 able to emit in the near infrared spectrum and make available the acquired spectra;
- a support 101, suitable for to acquire one or more biological fluid samples, preferably blood samples, concerning a specific user, and configured to be submitted to NIR scanning by means of the NIR spectrometer 102, so to detect the chemical substances comprised by the sample.
Moreover, the system 100 comprises:
- at least one data processing block 103 connected to the spectrometer 102 and configured to receive the spectrum acquired by means of the NIR spectrometer 102 and to process the data related to the acquired spectrum;
- at least one data management block 111 configured to archive the data acquired by means of the NIR spectrometer 102,
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to send and make available said data to the at least one data processing block 103, and to archive, in addition, the data processed by said at least one data processing block 103;
- at least one physical or logical interfacing device 104, able to start and manage the system 100 and configured for distributing in real-time the data analyzed by the at least one data processing block 103;
- a sorting center 110 equipped with a local or remote data connection with: the NIR spectrometer 102, the data management block 111, and the at least one data processing block 103.
According to the present invention, the system 100 comprises a plurality of sensors 105 that comprises at least one camera, configured for example to detect digital photographic images, spectral images and signals in the visible and IR electromagnetic spectrum, in the visible, and UV (Ultraviolet).
The plurality of sensors 105, by the sorting center 110, is able to record signals from sensors. The data management block 111, by the device 104 I/O, is able to make data available out of the system 100.
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According to an aspect of the invention, said support 101 is treated with a chelating compound, said chelating compound being specific for the free electrolyte to be detected.
Advantageously, the support 101 treated with a chelating compound allows to bond almost immediately free ions of the electrolyte predetermined to detect in the biological fluid sample, and by indirect measure to detect the concentration of the free electrolyte.
According to an aspect of the invention, the free electrolyte detected by the system 100 is a free divalent electrolyte, as Zn+2, Ca+2, Pb+2, Mg+2.
According to an aspect of the invention, the data processing block 103 comprises an artificial intelligence system suitable for implementing specific machine learning algorithms.
According to an aspect of the invention, the interfacing device 104 comprises a quality control block 112, a pre- analytical scan preparation block 106, at least one standardized library 108, an artificial intelligence system 109 comprising specific and parameterized machine learning algorithms, at least one for each analyte to analyze.
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According to an aspect of the invention, the NIR spectrometer 102 is connected directly to the data processing block 103 by internet connection, so to send to said data processing block 103 the spectrum resulting from the analysis of the predetermined biological or hematic sample.
According to an aspect of the invention, the data processing block 103 could be a physical or virtual machine. The sorting center 110 is equipped with a local or remote data connection with: the NIR spectrometer 102, the data management block 111, the data processing block 103 and, if present, with the plurality of sensors 105.
According to an aspect of the invention, the interfacing device 104 comprises: a log-in system for a plurality of users, and/or a management system for the plurality of sensors 105, and/or a management system for the NIR spectrometer 102, and/or a management system able to process historical data concerning the performed analysis, and/or a system for sending a draft concerning the analysis to an accredited professional/biologist, and/or a connection system with a LIS, LIMS system.
According to an aspect of the invention, the support 101 is consisting of tissue paper, preferably as a non-limiting
10
example, of a commercially available type as Whatman 903 protein saver. According to an aspect of the invention, the support 101 is consisting of a Guthrie paper on which are indicated specific data of the patient. The support is treated with a chelating compound, said chelating compound being specific for the free electrolyte to be detected.
In use, the NIR spectrometer 102 acquires the biological fluid or hematic sample and analyzes it performing a predetermined number N of scans for each spot of the patient. For example, performed scans are 32 for 3 spots of a patient.
Data of the spectrum obtained from scans are automatically sent to the sorting center 110 and from the sorting center 110 to the data processing block 103. The data processing block 103 is configured to perform post processing phases and analysis of received data, and to send it in real time, after validation, to the interfacing device 104 which is placed at the patient and/or at its doctor.
According to an aspect of the invention, the artificial intelligence system 109 is initially trained by a plurality of NIR spectrum related to set of training samples classified on the basis of levels of free electrolytes detected, or of free divalent ions like for example Calcium, by using a standard
11
method. Samples are applied to the support 101, that is a paper like "Guthrie card" pretreated with the suitable chelating compound (as an example for the measurement of free Calcium, it could be used EDTA or Ethylenediaminetetraacetic acid), to trap Calcium ions in a complex which is more easily detectable with NIR spectroscopy.
Alternatively, according to an aspect of the invention, the artificial intelligence system 109 is trained by NIR spectroscopy of a standard solution of Calcium with concentration between 7 mg/dl and 112 mg/dl. The standard solution in this case is applied to the support 101 as DBS pretreating with EDTA like chelating compound to chelate Calcium ions, generating a complex more detectable with NIR spectroscopy. The model obtained by the artificial intelligence system 109 is then validated through a double procedure, firstly by a validation set made by Calcium solutions with different concentrations selected casually, and then on a set of patients selected on the basis of its specific clinical condition after parathyroidectomy operations. If Calcium has to be measured, the support 101 is pretreated with EDTA as chelating compound.
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Moreover, according to an aspect of the invention, the artificial intelligence system 109 is trained by a set of hematic samples previously dosed for the concentration of free Calcium. Said samples are applied to the support 101 previously treated with a chelating compound. After chelating the free Calcium ion, it is generated a specific NIR signal which intensity is directly proportional to the amount of Calcium in the sample. The model obtained by the artificial intelligence system 109 is then validated through a double procedure, firstly by a validation set made by Calcium solutions with different concentrations selected casually, and then on a set of patients selected on the basis of its specific clinical condition after parathyroidectomy operations. Hematic samples in this case are applied to the support 101 pretreated with a fluorescent agent associated to the chelating compound.
According to an aspect of the invention, the support 101 comprises a barcode and a pre-forated section so to separate a first part comprising hematic samples, or in general biological samples, and a second part comprising patient's data. Separating the support 101 in two parts along the pre-forated section, the barcode is divided in two symmetrical parts, so to be readable on both parts. The barcode and a serial number
13
associated to the support 101 are uniquely associated to the patient by the image acquisition by device 104.
According to the invention, a first part of the support 101 comprising hematic spots could be also be sent by post or courier to a laboratory for types of analysis that cannot be performed by NIRS, like for example genetic tests or infectious tests, while a second part of the support 101 comprising the barcode and personal details would be a receipt and traceability receipt of the sent sample. Advantageously, the first part of the support 101 comprising hematic spots or biological fluid is easily transportable and mailable because it is thin, light and anonymous.
More in detail, the systema 100 comprises: - at least one "local group" 120 consisting of: at least one support 101 for at least one sample to be analyzed; at least one NIR spectrometer 102 configured to acquire the spectrum of said at least one sample; at least one physical or logical interfacing device 104. According to an aspect of the invention, the local group
120 is connected to the sorting center 110 by a remote data connection.
14
According to an aspect of the invention, the at least one interfacing device 104 is able to start and manage the system 100 and is configured for receiving in real-time the data analyzed by the at least one data processing block 103. According to an aspect of the invention, the NIR spectrometer 102 is a portable spectrometer.
According to an aspect of the invention, the NIR spectrometer 102, sensors 105, and the interfacing device 104 are connected to the sorting center 110 by internet connection. As previously mentioned, the present invention is related also to a method for monitoring levels of free electrolytes in biological samples and in particular to free Calcium in hematic samples.
In particular, the method of acquisition, transmission and processing of data according to the invention comprises the following steps:
- Acquiring a small amount of biological fluid, or of a blood sample of the patient, for example by sting of a finger; - Placing the biological fluid sample or hematic sample over a support 101;
15
Submitting the sample placed over the support 101 to NIR spectroscopy by means of a NIR spectrometer 102 and acquiring the spectrum of the sample by means of NIR spectroscopy; - Sending the acquired spectrum and other data to a sorting center 110 configured to perform the transmission of said spectrum and other acquired data to at least one processing block, and to store in the database the data and the processing, and send the data to an interfacing device 104;
Issuing an output signal related to the conformity or non conformity of the spectrum and/or data with respect to predefined values.
According to an aspect of the invention, the step of submitting the sample placed over the support 101 to NIR spectroscopy comprises:
Performing the acquisition of a plurality of NIRS spectrum, preferably at least five NIRS spectrum, of the sample. According to an aspect of the invention, the method comprises moreover:
16
- Analyzing data related to the spectrum by a block for the quality control;
- Analyzing data related to the spectrum by a block for the pre-analytic preparation of scans; - Submitting data related to the spectrum to one or more standardized libraries;
Submitting data related to the spectrum to one or more blocks comprising specific and parameterized machine learning algorithms. According to an aspect of the invention, the step of placing the biological fluid sample over the support 101 could be repeated more times because the patient repeats the operation for one or more spots.
According to another aspect of the invention, the steps of sending the spectrum obtained from the data processing block 103 and transmitting in real time to the device 104 the result related to the concentration of free electrolytes, in particular of free Calcium in the hematic sample, occurs by internet connection. According to an aspect of the invention, the step of processing the result related to the concentration of free electrolytes, or in particular of free Calcium in the analyzed
17
hematic sample, occurs by applying machine learning algorithms optimized for the free Calcium, not excluding the application of more specific methods for a more accurate prediction. For this purpose, are used methods for automatic training ("machine learning") alone or combined, as previously described.
Advantageously, the system and the method for monitoring levels of free electrolytes in biological fluids according to the invention, could be performed without taking a biological fluid sample by medical staff or paramedic staff, the sending of the sample to an analysis laboratory and waiting for the processing of the related result.
Advantageously according to the invention, the system and the method described allow to perform the domestic monitoring of levels of free electrolytes, and in particular of free divalent electrolytes, monitoring for example calcemia and so to allow to modify, on the basis of the obtained values, the dosage of the conventional therapy.
Advantageously, the monitoring of levels of free electrolytes by the system and the method according to the invention, and in particular of calcemia, allows a better control of the disease, improving the work life and the psycho physical health and reducing erroneous accesses to emergency
18
room and reducing the requirement of the established laboratory analysis for Calcium, involving a substantial economic saving.
It is clear, lastly, that the system and the method for monitoring levels of free electrolytes in biological fluids according to the described and illustrated invention could be modified without, for this reason, exit from the scope of protection of the present invention, as defined by the enclosed claims.
19
Claims
1. System (100) for monitoring levels of free electrolytes in biological fluids, able to monitor the concentration of at least one free electrolyte in at least one biological sample of at least one user, comprising:
- a NIR spectrometer (102) able to emit in the near infrared spectrum and make available the acquired spectra; a support (101), able to acquire one or more biological fluid samples concerning the specific user, and configured to be submitted to NIR scanning by means of the NIR spectrometer (102);
- at least one data processing block (103) configured to receive the spectrum acquired by means of the NIR spectrometer (102) and to process the data related to the acquired spectrum;
- at least one data management block (111) configured to archive the data acquired by means of the NIR spectrometer
(102), to send and make available said data to the at least one data processing block (103), and to archive, in addition, the data processed by said at least one data processing block
(103);
- at least one physical or logical interfacing device
(104), able to start and manage the system (100) and
20
configured for distributing in real-time the data analyzed by the at least one data processing block (103);
- a sorting center (110) equipped with a local or remote data connection with: the NIR spectrometer (102), the data management block (111), the at least one physical or logical interfacing device (104), and the at least one data processing block (103); characterized in that said support (101) is treated with a chelating compound, said chelating compound being specific for the free electrolyte to be detected.
2. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in that said at least one free electrolyte is present in a divalent ionic form. 3. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in comprising a plurality of sensors (105) comprising at least one camera.
4. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in that said at least one interfacing device (104) comprises an artificial intelligence system (109) implementing specific and parameterized artificial intelligence algorithms, a quality control block (112), a
21
pre-analytical scan preparation block (106), at least one standardized library (108).
5. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in that the at least one physical or logical interfacing device (104) comprises: a log-in system for a plurality of users, and/or a management system for the plurality of sensors (105), and/or a management system for the NIR spectrometer (102), and/or a management system able to process historical data concerning the performed analysis, and/or a system for sending a draft concerning the analysis to an accredited professional/biologist, and/or a connection system with a LIS, LIMS system.
6. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 3, characterized in that said plurality of sensors (105) comprises a camera and a system configured to acquire an image related to the support (101) and to decode personal data included in said support, and to send said data to the sorting center (110) to make them available to the system (100).
7. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in that said support (101) consists of a
22
Guthrie card on which the identification data of the patient are specified.
8. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in that said levels of free electrolytes consist of free calcium level, and in that said biological fluids consist of a blood sample.
9. System (100) for monitoring levels of free electrolytes in biological fluids according to claim 1, characterized in comprising: at least one "local group" (120) consisting of: at least one support (101) for at least one sample to be analyzed; at least one NIR spectrometer (102) configured to acquire the spectrum of said at least one sample; at least one physical or logical interfacing device (104).
10. Method for monitoring levels of free electrolytes in biological fluids, comprising the steps of:
- Acquiring a small quantity of biological fluid, or of a blood sample; - Placing the biological fluid sample over a support (101)
- Submitting the sample placed over the support (101) to NIR spectroscopy by means of a NIR spectrometer (102) and acquiring the spectrum of the sample by means of
NIR spectroscopy;
23
Sending the acquired spectrum and other data to a sorting center (110) configured to perform the transmission of said spectrum and other acquired data to at least one processing block, and to store in the database the data and the processing, and send the data to an interfacing device (104);
Issuing an output signal related to the conformity or non-conformity of the spectrum and/or data with respect to predefined values.
24
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| EP21802821.5A EP4337935A1 (en) | 2021-05-13 | 2021-11-02 | System and method for monitoring levels of free electrolytes in biological fluids |
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|---|---|---|---|
| IT102021000012416 | 2021-05-13 | ||
| IT102021000012416A IT202100012416A1 (en) | 2021-05-13 | 2021-05-13 | System and method for monitoring free electrolyte levels in biological fluids |
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| WO2022238754A1 true WO2022238754A1 (en) | 2022-11-17 |
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| PCT/IB2021/060133 WO2022238754A1 (en) | 2021-05-13 | 2021-11-02 | System and method for monitoring levels of free electrolytes in biological fluids |
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|---|---|
| EP (1) | EP4337935A1 (en) |
| IT (1) | IT202100012416A1 (en) |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200030515A1 (en) * | 2018-07-27 | 2020-01-30 | Fresenius Medical Care Holdings, Inc. | Method for tailoring dialysis treatment based on sensed potassium concentration in blood serum or dialysate |
-
2021
- 2021-05-13 IT IT102021000012416A patent/IT202100012416A1/en unknown
- 2021-11-02 WO PCT/IB2021/060133 patent/WO2022238754A1/en active Application Filing
- 2021-11-02 EP EP21802821.5A patent/EP4337935A1/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200030515A1 (en) * | 2018-07-27 | 2020-01-30 | Fresenius Medical Care Holdings, Inc. | Method for tailoring dialysis treatment based on sensed potassium concentration in blood serum or dialysate |
Non-Patent Citations (1)
| Title |
|---|
| MATSUI AKIHIRO ET AL: "A near-infrared fluorescent calcium probe: a new tool for intracellular multicolour Ca2+ imaging", CHEMICAL COMMUNICATIONS, vol. 47, no. 37, 12 August 2011 (2011-08-12), UK, pages 10407 - 10409, XP055871320, ISSN: 1359-7345, DOI: 10.1039/c1cc14045k * |
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| EP4337935A1 (en) | 2024-03-20 |
| IT202100012416A1 (en) | 2022-11-13 |
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