DE102024107957B3 - Electrochemical sensor system for the analysis of body fluids - Google Patents

Abstract

An electrochemical sensor system for analyzing body fluids (35), whether blood, sweat or urine, has the following features:
a) the sensor system is a potentiometric sensor system,
b) the sensor system has:
first filament electrodes (10a) with a first functional substance (13a),
second filament electrodes (10b) with a second functional substance (13b),
optionally third filament electrodes (10c) with a third functional substance (13c),
optionally fourth filament electrodes with a fourth functional substance, etc. until:
optionally fifteenth filament electrodes with a fifteenth functional substance,
c) the first functional substance (13a) and second functional substance (13b) and the optional further functional substances (13c) of the respective filament electrodes (10a, 10b, 10c) are each different in order to react to ions of a body fluid (35) with a specific potential,
d) the respective filament electrodes (10a, 10b, 10c) are connected to a textile substrate (30) to be worn on the skin (36),
e) the respective filament electrodes (10a, 10b, 10c) are connected to a computer for data analysis to determine the type of body fluid,
f) the filament electrodes (10a, 10b, 10c) each have a filament (11) with a metallic outer surface,
g) an adhesion promoter layer (12) made of SiOx is arranged on the metallic outer surface of the jacket,
h) the adhesion promoter layer (12) made of SiOx has a thickness of 10 to 200 nm,
i) the respective functional substance (13a, 13b, 13c) is chemically bonded to the adhesion promoter layer (12).
The electrochemical sensor system can be used for medical monitoring of injured persons.

Description

The invention relates to an electrochemical sensor system for analyzing body fluids, whether they are blood, sweat or urine.

When providing first aid in disaster situations, a small number of rescue workers are faced with a large number of injured. The same applies to combat missions involving wounded personnel. Here, rescue workers must quickly decide, sometimes under enemy fire, where effective assistance is needed and ultimately can be provided. It is precisely in such complex situations that rescuers currently lack reliable information about the number of injured, their location, and the nature of their injuries.

The US 2023 / 0 072 912 A1 shows an electrochemical sensor system. The sensor system is a potentiometric sensor system. The sensor system has multiple measuring electrodes. Each of the multiple measuring electrodes can also have filament electrodes, among many other embodiments. The filament electrodes are connected to a textile substrate to be worn on the skin. In one embodiment, a sample of a body fluid can be urine, sweat, or blood.

The EP 3 385 708 A1 shows an electrochemical sensor system for analyzing body sweat. The sensor system can be based not only on the principle of a galvanic cell but also be a potentiometric sensor system. The sensor system comprises several measuring electrodes. Each of the several measuring electrodes comprises a filament electrode. Each filament electrode has at least one metallic outer surface. This is followed by a functional layer. In a specific embodiment, the filament electrode is woven into a textile substrate to be worn on the skin. In a specific embodiment, a silane substance is added to an enzyme solution before a filament electrode in the form of a textile fiber is functionalized. The enzyme/silane solution is mixed with a conductive polymer solution, and the combined solution is used to swell the textile fibers. The silane molecules reduce swelling and form a network of bonds. The network fixes the enzyme and the silane molecule to the fiber. The silane molecule is used to enclose it, together with the polymer, within the textile fiber.

The CN 1 06 568 823 A shows an electrochemical, potentiometric sensor system for distinguishing flavors (sour, sweet, bitter, salty, etc.). The sensor system consists of a sensor array, an automatic sample feeder, and a data acquisition system with data analysis software for data-analytical calculation of the flavor.

The invention is based on the EP 3 385 708 A1 The aim is to develop the electrochemical sensor system described therein for a different purpose.

The WO 2017 / 189 966 A1 shows an electrochemical sensor system for analyzing body fluids, whether they are blood, sweat or urine, with the features a) to f) and i) of claim 1.

The US 2020 / 0 363 367 A1 shows an electrochemical sensor system for analyzing body fluids, whether they are blood, sweat or urine, with the features a) to f) and of claim 1. The respective functional substances are bound directly to the metallic outer surfaces of the casing.

The DE 697 35 601 T2 relates to the field of biosensors with bilayer-compatible surfaces. In one embodiment, an electrode surface is coated with a thin layer of SiO ₂ . This layer forms the bilayer surface. In embodiments in which this layer is an insulating material, it is preferably less than about 1 nm thick to enable detection of capacitive transient currents caused by binding of ligands to ionophore receptors.

This object is achieved according to the invention by the features of claim 1.

• Mit dem elektrochemischen Sensorsystem zur Analyse von Körperflüssigkeiten wird analysiert, ob es sich bei einer Körperflüssigkeit um Blut, Schweiß oder Urin handelt. Dies ist für eine ärztliche Überwachung von Verwundeten bedeutsam. Das Sensorsystem ist ein potentiometrisches Sensorsystem. Das Sensorsystem weist auf:
• erste Filamentelektroden mit einer ersten Funktionssubstanz,
• zweite Filamentelektroden mit einer zweiten Funktionssubstanz,
• fakultativ dritte Filamentelektroden mit einer dritten Funktionssubstanz,
• fakultativ vierte Filamentelektroden mit einer vierten Funktionssubstanz, ...,
• fakultativ fünfzehnte Filamentelektroden mit einer fünfzehnten Funktionssubstanz.

The advantages of the invention result from the following features:

• The electrochemical sensor system for analyzing body fluids analyzes whether a body fluid is blood, sweat, or urine. This is important for medical monitoring of wounded patients. The sensor system is a potentiometric sensor system. The sensor system features:
• first filament electrodes with a first functional substance,
• second filament electrodes with a second functional substance,
• optionally third filament electrodes with a third functional substance,
• optionally fourth filament electrodes with a fourth functional substance, ...,
• optionally fifteenth filament electrodes with a fifteenth functional substance.

The first and second and optionally further functional substances of the respective filament electrodes each have a different functional substance in order to react to ions of a body fluid with a specific potential.

The respective filament electrodes are connected to a textile substrate worn on the skin. The respective filament electrodes are connected to a computer for data-analytical calculation of the type of body fluid. The filament electrodes comprise a filament with a metallic outer surface. Particular advantages and surprising effects arise from the fact that an SiO _x adhesion promoter layer is arranged on the metallic outer surface, that the SiO _x adhesion promoter layer has a thickness of 10 to 200 nm, and that the functional substance is chemically bonded to the adhesion promoter layer. The respective functional substance is chemically bonded to the adhesion promoter layer. The chemical functional substances are specifically selected and permanently immobilized on the electrode surface as a nanolayer using SiO x. The particular advantages and surprising effects are that, despite the chemical bond, the chemical functionality is retained and the potential of the chemically modified electrode specifically changes upon contact with the body fluids to be detected. Furthermore, the chemical functionality is covalently and thus permanently fixed to the electrode surface via the adhesion promoter layer. EDX analyses have shown that adhesion promoter layers thinner than 10 nm do not provide sufficient chemical bonding of the functionalizations, and that adhesion promoter layers thicker than 200 nm influence the electrode potentials, so that the SiO _x layer, rather than the chemical functionalization, determines the electrode potential.

According to an advantageous embodiment of the invention, the adhesion promoter layer is obtained by a flame-pyrolytic combustion-chemical vapor deposition (C-CVD) process. This is the preferred process for large-scale production.

According to a further advantageous embodiment of the invention, the adhesion promoter layer is obtained by cathodically induced polymerization of silica. Although too complex for large-scale production, the process is suitable for the production of prototypes. This is because the application of the adhesion promoter layer and the subsequent application of the functional substance can be carried out after the filaments have been incorporated into the textile substrate using textile technology.

According to a further advantageous embodiment of the invention, the first functional substance chemically bonded to the SiOx adhesion promoter layer comprises a methoxysilane. Trimethoxysilanes react particularly to ions from blood and urine.

According to a further advantageous embodiment of the invention, the first functional substance chemically bonded to the SiOx adhesion promoter layer comprises an aminothiol. Aminothiols react particularly to blood ions.

According to a further advantageous embodiment of the invention, the sensor system comprises a third functional substance chemically bonded to the SiOx adhesion promoter layer. The third functional substance comprises a substance from the group consisting of Levafin blue, homocysteine, and Lupamin 9095. These substances react particularly to blood ions.

According to a further advantageous embodiment of the invention, the first filament electrodes are contained in first yarns that are textile-technically incorporated into a first electrode track in the textile substrate. The second filament electrodes are contained in second yarns that are textile-technically incorporated into a second electrode track in the textile substrate. The optionally further filament electrodes are each textile-technically incorporated into further respective yarns in the textile substrate in a further electrode track. The individual electrode tracks allow easy connection to a textile circuit with a computer (microcontroller).

According to a further advantageous embodiment of the invention, the sensor system does not have a reference electrode in addition to the filament electrodes. This reduces manufacturing costs on the one hand, but on the other hand, it reduces the quality of the measured values. However, this does not pose a problem for a data analysis calculation to determine the type of body fluid if a neural network is used for the data analysis calculation.

According to a further advantageous embodiment of the invention, the sensor system comprises a reference electrode in addition to the filament electrodes. This improves the quality of the measured values, but at the expense of increased manufacturing effort.

• 1 ein textiles Sensorsystem aufweisend eine Schaltung mit einem Computer, als perspektivische Darstellung;
• 2 eine Filamentelektrode, als perspektivische Darstellung;
• 3 eine Referenzelektrode, als perspektivische Darstellung;
• 4 ein zweites Textilsubstrat, in der Draufsicht, abgeleitet von einem Foto, mit händisch ergänzten Profilansichten;
• 5 und 6 jeweils eine Illustration einer Filamentelektrode bezüglich einer Haftvermittlerschicht und einer Funktionssubstanz.

Embodiments of the invention are explained in more detail below with reference to the drawings tert. Here, simplified schematic diagrams show:

• 1 a textile sensor system comprising a circuit with a computer, as a perspective view;
• 2 a filament electrode, as a perspective view;
• 3 a reference electrode, as a perspective view;
• 4 a second textile substrate, in plan view, derived from a photograph, with manually added profile views;
• 5 and 6 an illustration of a filament electrode with respect to an adhesion promoter layer and a functional substance.

• • erste Filamentelektroden 10a mit einer ersten Funktionssubstanz 13a,
• • zweite Filamentelektroden 10 b mit einer zweiten Funktionssubstanz 13b,
• • und dritte Filamentelektroden 10c mit einer dritten Funktionssubstanz 13c.

In detail on the general structure of the sensor system, the 1 An electrochemical sensor system for analyzing body fluids 35 to determine whether they are blood, sweat, or urine. The sensor system is a potentiometric sensor system. The sensor system comprises:

• • first filament electrodes 10a with a first functional substance 13a,
• • second filament electrodes 10 b with a second functional substance 13 b,
• • and third filament electrodes 10c with a third functional substance 13c.

The first functional substance 13a, the second functional substance 13b, and the third functional substance 13c of the respective filament electrodes 10a, 10b, 10c are different in order to react to ions of the body fluid 35 with a specific potential. Body fluids 35 contain different ions in different amounts. These cause a respective potential depending on the type of body fluid 35 with respect to a respective functional substance.

The general structure of the 1 shown filament electrodes 10a, 10b, 10c is in 2 shown. The 2 The filament electrode 10 shown in the general structure has a filament 11 with a metallic outer surface. In the present example, the filament 11 with the metallic outer surface is a core filament (polyamide) 11a with a metal layer (silver, 1 µm) 11b. An adhesion promoter layer 12 made of SiOx is arranged on the filament 11 with the metallic outer surface. The adhesion promoter layer 12 made of SiOx has a thickness of 10 to 200 nm. A functional substance 13 is chemically bonded to the adhesion promoter layer 12.

The respective filament electrodes 10a, 10b, 10c are connected to a textile substrate 30 to be worn on the skin 36. The respective filament electrodes 10a, 10b, 10c are connected to a circuit 80 with a computer 85 in the form of a microcontroller for data-analytical calculation of the type of body fluid 35. The circuit also includes a Bluetooth transmitter 87 for transmitting the data to a physician. If, for example, the body fluid 35 is blood, the physician can initiate countermeasures early on.

Looking at the details of the adhesion promoter layer, the adhesion promoter layer 12 is obtained using a flame-pyrolytic combustion-chemical vapor deposition (C-CVD) process. A C-CVD system for carrying out this process has a filament unwinding and winding system. The adhesion promoter layer 12 is applied by passing a filament 11 with a metallic surface through a flame. In the C-CVD technique, this flame is fed with an organic silane, the so-called precursor. The combustion of the silane in the flame creates highly reactive H ₄ SiO ₄ fragments, which are deposited on the metallic surface of the filament 11 and form a nanoscale SiOx layer. The advantage of this process is its high process speed and stability. However, the reactivity of the nanolayers decreases so much after just 48 hours that a stable chemical modification is hardly possible. This means that the filaments treated in this way must be chemically modified in a timely manner.

An adhesion promoter layer 12 is alternatively obtained by cathodically induced polymerization of silica. Cathodically induced polymerization is ideally suited for the production of a prototype. A prototype can be obtained by applying an adhesion promoter layer and applying a functional substance after textile-technological incorporation, since contact paths are present and allow connection to a voltage source. In order to first apply an adhesion promoter layer in a suitable electrolyte, such as silica, and then, after washing and cleaning, electrochemically apply the functional substance.

In-depth details of the functional substances, illustrated 5 that a first functional substance 13a chemically bonded to the SiOx adhesion promoter layer 12 comprises a methoxysilane as the functional substance. First example of a methoxysilane: 3-aminopropyltrimethoxysilane. Second example: 3-glycidyloxypropyltrimethoxysilane.

6 illustrates that a second functional substance 13b chemically bonded to the SiOx adhesion promoter layer 12 has an aminothiol as its functional substance. The first example of an aminothiol is 3-amino-1,2,4-triazole-5-thiol. The second example is 2-aminoethanethiol.

A third functional substance 13c (without figure) chemically bonded to the SiOx adhesion promoter layer 12 comprises: a functional substance from the group of substances consisting of Levafin blue, homocysteine and Lupamin 9095.

The respective functional substances are dissolved in a solvent and react with the reactive, freshly applied adhesion promoter layer. This immobilizes the respective chemical modification on the respective filament electrode. Specifically: To apply the functional substance, the filament is unwound and passed through an ethanol solution containing the respective functional substance. The resulting filament electrode is then dried in a heating tube and rewound.

Going into details of the electrode tracks, the first filament electrodes 10a are contained in first yarns and the first yarns are textile-technically incorporated into a first electrode track 50a in the textile substrate 30. The second filament electrodes 10b are contained in second yarns and the second yarns are textile-technically incorporated into a second electrode track 50b in the textile substrate 30. The third filament electrodes 10c are textile-technically incorporated into third yarns in the textile substrate 30 in a third electrode track 50c. The electrode tracks 50a, 50b, 50c are woven into the textile substrate at a distance from contact tracks 81a, 81b and 81c. Secure contact between the contact tracks and the electrode tracks can be achieved using a film loaded with conductive particles under the influence of heat and pressure.

4 shows another textile substrate 30'. The electrode tracks 50a', 50b', and 50c' each have three flat yarns woven side by side, each with identical filament electrodes 10a, 10b, 10c.

Going into details regarding reference electrodes, the 1 The sensor system shown does not have a reference electrode in addition to the filament electrodes 10a, 10b, 10c. The potential voltages between the individual filament electrodes 10a, 10b, 10c are tapped from each other.

According to a further example, the sensor system also comprises a reference filament electrode 20 in addition to the filament electrodes 10a, 10b, 10c.

The 3 shows the structure of a reference filament electrode 20. The reference filament electrode 20 comprises a filament 21 with a metallic sheath surface, an adhesion promoter layer 22 made of SiO _x , an AgCl layer 27, a layer 28 with a KCl solution and a membrane layer 29. The reference filament electrode 20 is a type 2 electrode with a constant electrode potential (metal/sparingly soluble salt of the metal/electrolyte with the counter ions of the sparingly soluble salt).

The reference filament electrode 20 can be integrated into the sensor system as follows (not shown): A silver wire coated with AgCl is woven into a textile. The fabric is then sealed with a breathable yet waterproof membrane. A saturated KCl solution is then applied to the sealed textile. Finally, the areas where the electrolyte was applied through the membrane are sealed.

• • Gemäß der Ausführungsbeispiele weist das Sensorsystem auf: Erste Filamentelektroden 10a mit einer ersten Funktionssubstanz 13a, zweite Filamentelektroden 10 b mit einer zweiten Funktionssubstanz 13b, und dritte Filamentelektroden 10c mit einer dritten Funktionssubstanz 13c. In Abweichung hierzu können ergänzt sein: fakultativ zusätzlich vierte Filamentelektroden mit einer vierten Funktionssubstanz oder wiederum fakultativ zusätzlich fünfte Filamentelektroden mit einer fünften Funktionssubstanz, usw. bis maximal fünfzehnte Filamentelektroden mit einer fünfzehnten Funktionssubstanz. Die weiteren Filamentelektroden sind jeweils in weitern Garnen im Textilsubstrat in jeweils weiteren Elektrodenbahnen eingewebt oder anderweitig textiltechnologisch eingearbeitet.
• • Gemäß den Ausführungsbeispielen werden sowohl für die Filamentelektroden als auch für mögliche Referenzfilamentelektroden Filamente mit einer metallischen Manteloberfläche verwendet, die ein Kernfilament aus Kunststoff und eine Metallschicht aufweisen. Alternativ können auch Metallfilamente, wie Silberdrähte, eingesetzt werden.
• • Die jeweiligen Filamentelektroden 10a, 10b, 10c sind an einen Computer zur datenanalytischen Berechnung zur Bestimmung der Körperflüssigkeit 35 angeschlossen. In den Ausführungsbeispielen wird ein neuronales Netzwerk verwendet. Möglich wäre auch eine etwas einfacher durchführbare multivariate Datenanalyse, insbesondere dann, wenn Referenzfilamentelektroden zum Einsatz kommen und Messwerte hoher Qualität liefern.

In deviation from the previous embodiments, the following modifications are possible:

• • According to the exemplary embodiments, the sensor system comprises: first filament electrodes 10a with a first functional substance 13a, second filament electrodes 10b with a second functional substance 13b, and third filament electrodes 10c with a third functional substance 13c. In deviation from this, the following can be added: optionally additional fourth filament electrodes with a fourth functional substance or, again optionally, additional fifth filament electrodes with a fifth functional substance, etc. up to a maximum of fifteenth filament electrodes with a fifteenth functional substance. The further filament electrodes are each woven into further yarns in the textile substrate in further electrode tracks or are otherwise incorporated using textile technology.
• • According to the exemplary embodiments, filaments with a metallic sheath surface are used for both the filament electrodes and possible reference filament electrodes. These filaments comprise a plastic core filament and a metal layer. Alternatively, metal filaments, such as silver wires, can also be used.
• • The respective filament electrodes 10a, 10b, 10c are connected to a computer for data analysis calculation to determine the body fluid 35. In the embodiments, a neural network A somewhat simpler multivariate data analysis would also be possible, especially if reference filament electrodes are used and provide high-quality measurements.

List of reference symbols:

10

Filament electrode

10a

first filament electrode

10b

second filament electrode

10c

third filament electrode

11

Filament with a metallic sheath surface

11a

core filament

11b

metal layer

12

Adhesion promoter layer made of SiO _x

13

Functional substance

13a

first functional substance

13b

second functional substance

13c

third functional substance

20

Reference filament electrode

21

Filament with a metallic sheath surface

21a

core filament

21b

metal layer

22

Adhesion promoter layer made of SiOx

27

AgCl layer

28

Layer with KCI solution

29

Membrane layer

30

Textile substrate

35

Body fluid

36

skin

50a

first electrode track

50b

second electrode track

50c

third electrode track

80

Textile circuit with computer

81a

Contact path

81b

Contact path

81c

Contact path

85

computer

87

Bluetooth transmitter

Claims (9)

An electrochemical sensor system for analyzing body fluids (35), whether they are blood, sweat, or urine, having the features: a) the sensor system is a potentiometric sensor system, b) the sensor system comprises: first filament electrodes (10a) with a first functional substance (13a), second filament electrodes (10b) with a second functional substance (13b), optionally third filament electrodes (10c) with a third functional substance (13c), optionally fourth filament electrodes with a fourth functional substance, ..., optionally fifteenth filament electrodes with a fifteenth functional substance, c) the first functional substance (13a) and second functional substance (13b) and the optionally further functional substances (13c) of the respective filament electrodes (10a, 10b, 10c) are each different in order to react to ions of a body fluid (35) with a specific potential, d) the respective filament electrodes (10a, 10b, 10c) are connected to a textile substrate (30) to be worn on the skin (36), e) the respective filament electrodes (10a, 10b, 10c) are connected to a computer for data-analytical calculation to determine the type of body fluid (35), f) the filament electrodes (10a, 10b, 10c) each have a filament (11) with a metallic outer surface, g) an adhesion promoter layer (12) made of SiO _x is arranged on the metallic outer surface, h) the adhesion promoter layer (12) made of SiO _x has a thickness of 10 to 200 nm, i) the respective functional substance (13a, 13b, 13c) is chemically bonded to the adhesion promoter layer (12). Sensor system according to Claim 1 , in which the adhesion promoter layer (12) is obtained by a flame pyrolytic combustion-chemical vapor deposition (C-CVD) process. Sensor system according to Claim 1 , in which the adhesion promoter layer (12) is obtained by cathodically induced polymerization of silica. Sensor system according to one of the Claims 1 until 3 , in which the first functional substance (13a) comprises a methoxysilane. Sensor system according to one of the Claims 1 until 4 , in which the second functional substance (13b) comprises an amino-thiol. Sensor system according to one of the Claims 1 until 5 , in which the third functional substance (13c) comprises a substance from the group of substances consisting of Levafin blue, homocysteine and Lupamin 9095. Sensor system according to one of the Claims 1 until 6 , in which the first filament electrodes (10a) are contained in first yarns and the first yarns are textile-technically incorporated into a first electrode track (50a) in the textile substrate (30), in which the second filament electrodes (10b) are contained in second yarns and the second yarns are textile-technically incorporated into a second electrode track (50b) in the textile substrate (30), in which the optionally further third to fifteenth filament electrodes (10c) are textile-technically incorporated into third to fifteenth yarns in the textile substrate (30) in a third to fifteenth electrode track (50c). Sensor system according to one of the Claims 1 until 7 which has no reference electrode in addition to the filament electrodes (10a, 10b, 10c). Sensor system according to one of the Claims 1 until 7 which, in addition to the filament electrodes (10a, 10b, 10c), also has a reference electrode.

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