Ion-selective electrode arrangement

(42) Date of commencement of the patent: 15. 1. 1994 (45) Date of issue: 26. 9.1994 (51) Int.Cl.⁵ : G01N 27/414 GO1N 27/30

<td>(56) Documents:</td><td>(73) Patent owner:</td>

<td>EP-A2 0291904 EP-A2 0241991 US-PS 4603372 AT-PS-E 24970 EP-A2 0307973 EP-A2 0228969</td><td>3ACHIM0WICZ ARTUR DIPL.ING. A-1220 VIENNA (AT). KEPLINGER FRANZ DIPL.ING. A-1090 VIENNA (AT). URBAN GERALD DIPL.ING. DR. A-1020 VIENNA (AT). GLOSS RONALD A-1030 VIENNA (AT).</td>

The invention relates to an ion-selective electrode arrangement (ISE), in which an electrode (2) is applied to an insulator (1), which is covered with at least one insulating layer (3), except for a window with an ion-selective membrane (9) is covered, wherein the electrode (2) is optionally covered by at least one further conductive layer is auf'die electrode (2) or if appropriate, a metal layer (4) and then a layer (5) of a sparingly soluble salt are applied to this further layer. On the layer (5) of sparingly soluble salt, a solid internal electrolyte (6) of the formula X-halide, preferably X-chloride, is applied, where X is the ion to be measured in the measuring solution to which the ion-selective membrane (9) in the main thing sensitive or is selective or X is an ion to which the membrane (9) is not mainly specific sensitive or selectively

CD is; on this inner electrolyte (6), the ion-selective membrane (9) is applied. According to the invention it is provided that the solid internal electrolyte (6) has high purity (less 0.1 S impurities).

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AT 398 133

MR 0078013

AT 398 133 Β

The invention relates to an ion-selective electrode arrangement (ISE), in which on one, optionally the gate insulator or the gate oxide of an IFSETS representing insulator, a planar, conductive electrode or Electrode layer is applied, which is covered with at least one insulating layer, preferably of SiOx, SiNx, polyimide or polymethacrylate, to at least one window, wherein the window is covered with an ion-selective membrane, wherein for protection or for stabilizing the conductive electrode, the electrode of at least one further applied to the electrode conductive layer, preferably from a relation to the electrode material, different material, eg different metal, in particular gold, or different compound, is covered, wherein on this further layer a metal layer, preferably Ag or La, and thereon a layer of a sparingly soluble salt, in particular a halide of this metal, preferably AgCl or LaF3, where X is the ion to be measured in the measurement solution, to which the ion-selective membrane is mainly sensitive or is selective or X is an ion to which the membrane is not specifically sensitive or is selective, and wherein on this inner electrolyte, the ion-selective membrane is applied.

Sensors of this type are known, for example, from EP-A2-241991. In this known arrangement, the inner electrolyte is present in distributed form in a polymer matrix, whereby optimal reaction conditions can not be achieved and drift sensitivity voriiegt.

In particular, in the chemical analysis, medical diagnostics and biotechnical process control, there is a great need for sensors for the detection of ionic activities, such as Hydrogen, potassium, sodium or other ions. The easiest way to measure these parameters is with ion-selective electrodes (ISE). These electrodes allow the measured quantity to be converted directly into an electrical signal at the measuring location. Such ion-selective electrodes based on the principle of ion-selective membrane are available for a variety of ions. In particular, the development of lipophilic neutral ion carrier molecules has paved the way for the production of highly selective ISE.

The well-known ISE, however, do not meet the requirements of modern medicine. Miniaturized, cheap disposable sensors would be an advantage for outpatient or acute medical care, as well as in vivo monitoring of relevant electrolytes would be important for the intensive care unit. In addition, however, the simultaneous determination of several ions in modern diagnostics is also advantageous. However, all these requirements can not be met with the conventional ISE, since they are not easily miniaturized, are not well suited for mass production and can not be integrated, and do not permit reliable long-term measurements.

The invention eliminates these disadvantages and, in the case of an ion-selective electrode arrangement of the type mentioned at the outset, according to the invention provides that the solid inner electrolyte has high purity (less than 0.1% impurities).

The electrode arrangement according to the invention makes it possible to convert the measured variable directly at the measuring location into precisely defined electrical signals, provides very accurate results without significant drift and is easy to use. Furthermore, the electrode arrangement according to the invention is suitable for mass production in thin-film technology.

The structure of the electrode arrangement according to the invention described in more detail below enables a good cohesion or Good mutual adhesion of the individual layers applied, in particular the ion-selective membrane and the inner electrolyte and the ability to form a stable potential through the defined and compact, solid internal electrolyte. Which consists of several planar layers or Layer parts existing ion-selective electrode assembly can by appropriate methods of thin-film technology, such as Vapor deposition, sputtering, plasma erosion or the like getting produced. Such arrangements are cheap to build, can be integrated with other electronic and electrical components and used in medicine and biology as a disposable sensor; also the attachment to a catheter, eg to carry out measurements in whole blood, is without further possible, a measurement method that has not been satisfactorily resolved.

Preferred embodiments of the invention will become apparent from the following description, the claims and the drawings.

In the following the invention will be explained in more detail with reference to the drawing, for example. 1, 2, 3 and 4 schematically show the basic structure of ion-selective electrical arrangements. FIG. FIG. 9 shows a preferred embodiment of the invention, FIG. 5 shows the combination of an inventive electrode arrangement with an ISFET, FIG. 11 shows an electrode arrangement on a catheter, and FIG flow measurement.

1 shows a simple structure of an electrode arrangement, consisting of an insulating substrate 1, or a corresponding insulating layer, for example made of glass or a metal substrate insulated with a silicon nitride layer, onto which insulating layer 1 a conductive layer 2 is applied

AT 398 133 B

Electrode layer acts. This layer 2 may be made of a metal, such as Titanium, platinum, silver from semiconductors, eg Germanium, Sicilium, or of conductive plastics, eg Polypyrene or the like. consist. This conductor 2 is from one (or more) insulation layer 3, eg made of silicon nitride, polyimide or the like., Covered. The actual electrode surface (one or more) remains through an opening 10 (resp. a number of openings) in the insulating layer 3 in a defined manner and is covered with an ion-selective membrane 9.

Since the ion-selective membrane has a high level of plasticizer, typically about 66%, adhesion problems may occur depending on the material to which the ion-selective membrane is applied. With silicon or silicon nitride as the base layer, the adhesion between the insulating layer and the membrane can be improved by ensiling, for example with HMDS or hexamethyldisilazane or a similar agent.

2 shows an arrangement in which the conductive electrode 2 is bounded on both sides by the insulating layer 3 and the contacting of the conductive electrode 2 by means of a conductive material 11, which is formed in a passage or bore in a base body 1. This contacting can occur instead of the conductor 2a shown in FIG.

3 shows an arrangement in which the adhesion between the membrane 9 and the insulating layer is improved by an adhesive layer 8. This adhesive layer 8 can, for example form a chemical compound with the membrane, so that optimum adhesion is achieved. This adhesive layer 8 can be omitted if the insulating layer 3 is simultaneously formed as an adhesive and insulating layer. 2 is on the substrate 1 with its conductive electrode 2, which is covered by the insulating layer 3 or is limited, preferably made of inorganic material such as silicon nitride or Silica or dioxide exists, the further insulating or Adhesive layer 8 applied, which preferably consists of polymethacrylate, in order to form a chemical compound with the above the opening 10 in the insulating layer 3 or Adhesive layer 8 to ensure lying ion-selective membrane 9. FIG. 3 further shows that a layer of redox polymer 6 'can be applied to a metal layer 4 applied to the electrode 2, on which the membrane 9 is applied, which can consist of polypryrene, polyaniline or polythiophene.

4 generally shows the structure of an ion-selective electrode arrangement, in which on an insulating substrate or Basic body 1, eg made of glass, a silicon nitride coated metal substrate or the like., A conductor 2 is arranged, from which by means of the insulating layer 3, for Silicon nitride or polyimide, an electrode is delimited. The remaining free electrode surface 2 is covered with a layer 4, which consists of a different material from the electrode material, eg different metal or compound is to ensure the electrode properties or the electrode against oxidation or the like. to protect. This layer 4 can be applied alone or in combination with another layer 5. In this case, the layer 4 consists of a metal and the layer 5 of a sparingly soluble salt (preferably halide) of this metal. The layer 4 can, for example consist of a precious metal, in particular gold, which has the advantage of low oxide occupancy and therefore ensures a defined surface potential. The layer 4 could also consist of silver and the layer 5 of silver chloride, which arrangement has a stable chloride potential as a second type of electrode.

5 shows an electrode arrangement according to the invention, in which the electrode 2 is covered with a layer 4 of a metal and this metal layer is covered with a layer 5 of a sparingly soluble salt of this metal. A conductive layer possibly applied directly to the electrode 2 for protection thereof is not shown. These metal salts are in particular the halides or Fluorides of these metals. Suitable metals for the layer 4 are in particular silver or lanthanum. The discharge electrode formed by the electrode 2 and the layers 4 and 5 and the insulating layer are supported by another layer or from an inner electrolyte 6 of a metal salt, in particular a metal halide, for example Sodium chloride, sodium fluoride, covered. Essential to the invention to obtain accurate measurement results is that the solid internal electrolyte has high purity (less 0.1% impurities). The solid inner electrolyte 6 may also be of a solid acid, eg Oxalic acid or a solid base, eg KOH, be formed. The inner electrolyte 6 contains the anion of the sparingly soluble metal salt (eg Vienna, September 20, 1993 CI for the silver chloride electrode) and cation of that ion to which the membrane is mainly selective (eg Sodium). If this substance can not be used for technological reasons, the cation can also be replaced by a cation to which the membrane reacts only selectively to a limited extent, although this layer must also consist of a high-purity material with a very low proportion of foreign substances. So could eg the layer 5 consist of highly pure NaCl, even if the membrane 9 specific or mainly responsive to potassium ions selectively.

5, the entire electrode arrangement or the layer of the inner electrolyte 6 is covered with a membrane 9, optionally with the aid of an adhesive layer 8,

AT 398 133 Β which extends advantageously below the layer of the inner electrolyte 6.

During the measurement, water is transported through the membrane 9 by the osmotic pressure. This process can also be used to transport water through any membrane 9, if it is needed for a measurement process below the membrane, eg for an amperometric oxygen measurement. This water forms a saturated solution with the metal salt of the inner electrolyte 6 and there is an inner electrolyte, the defined potentials at the Ableitelektrode, ie forms the layers 5 and / or 4 and the electrode 2 and on the membrane inside. These two potentials remain stable until the entire amount of the solid inner electrolyte, in particular the entire amount of salt has been dissolved. From this point on, a potential change begins (120 mV per concentration decade of the inner electrolyte). By the process just described, the life of the electrode assembly is limited. Such a sensor structure is therefore well used for short-term measurements (a few hours), especially for one-time measurements, this structure is satisfactory and sufficient.

So that such sensors or Electrode arrangements can also be used for other applications, eg for continuous postoperative control of potassium in the blood, a longer life (eg three days). To achieve this, on the one hand the essential for the function of the electrode assembly water transport through the membrane 9 must be kept as low as possible, on the other hand, however, the amount of metal salt should be as large as possible. However, since the resistance to water transport is proportional to the electrical resistance of the membrane 9, this condition results in a minimum thickness for the membrane.

In addition, to extend the life of an arrangement such in fig.6, to be chosen. Over the layer of the inner electrolyte, a Wasserhemmschicht 7 is applied, in the at least one opening or Pore ​​12 is provided. In fact, a plurality of pores or Openings 12 are provided, the diameter or Transfer routes on the order of a few micrometers, advantageously from about 20 to 40 micrometers possess. Thus, the water transport is limited by the size of the transfer path 12 in the water-barrier layer 7. Schematically, the transfer path through an opening 12 is shown in the drawing; In practice, this transfer path consists of a multiplicity of openings, each of which permits a certain transport of water. This water-repellent layer 7 consists in particular of inorganic material, eg SiNx into which openings are subsequently etched. This water-inhibiting layer 7 can also be formed by an organic polymer filter layer whose transfer cross-section enables water transport in a braked manner; Such organic layers are, for example Teflon, poly-HEMA or a conductive polymer layer, eg Polypyrene to produce.

In order to be able to anchor the membrane 9 better to the inner electrolyte 6, the ion-selective membrane 9 is arranged in the region between the inner electrode 6 and the Wasserhemmschicht 7 in a structure according to Figure 9. It would be sufficient to use existing membrane material between the water-inhibiting layer 7 and the inner electrolyte 6, but it is preferable for this membrane material to communicate with further membrane material disposed on the water-blocking layer 7 through the transfer openings 12, which may also be filled with membrane material. In this case, care must again be taken that the membrane 9 adheres well to the water-repellent layer 7, for which purpose adhesive layers similar to those as indicated by 8 can be used.

In the construction according to FIG. 9, the arrangement of membranes inside and outside the water-inhibiting layer 7 results in an arrangement in which the membrane 9 is pressed against the internal electrodes 6 by the osmotic pressure and thus fixed. This prevents an undefined flow of water.

7 shows an arrangement in which the lateral extent of the membrane 9 is limited by an annular boundary 13 of inorganic material, for example silicon nitride, or of organic material, for example polyimide or polymethyl methacrylate. At the same time this results in a protective effect against stripping of the membrane. 9

8 shows a further embodiment of an electrode arrangement according to the invention, in which the additional anchoring of the membrane 9 is effected by an adhesive layer 8 on the insulating layer 3. In addition to or instead of the adhesive layer 8, the membrane 9 is replaced by an outwardly tapered recess (funnel) 15 in a layer or Holding layer 44 held. This conical structure, which has a recessed cross section with a diameter on the electrode side enlarging diameter, for example be achieved by a polyimide layer or Poymethylmetacrylatschicht. Another design of this structure can eg be made by a structure of two layers, in which the insulating layer 14 consists of etched silicon and subsequently applied to the structure formed by the layers 1, 3 and 9, in particular glued. In this embodiment of an electrode arrangement shown in Figure 8, a support of the membrane 9 is achieved, so that against the osmotic pressure

AT 398 133 Β mechanical counterpressure, which not only achieves a mechanical fixation, but also a further water inhibition, especially when using a saturated inner electrolyte.

In particular, with such arrangements, it is easily possible to arrange or integrate several ion-selective electrode arrangements, in particular in combination with other sensors, for example temperature and / or oxygen sensors, on a support or a supporting layer.

The arrangements shown in FIGS. 7 and 8 can be realized in particular by means of microetched silicon by glass bonding or by the use of polymer adhesive layers. In this case, and also in the other electrode structures, the membrane 9 can be printed, which is then surrounded or covered with the cover layer 13 and 14 respectively.

10 shows an electrode arrangement in which the insulating layer 1 is formed as a gate of an ISFET. This structure offers a favorable data acquisition directly at the sensor. 10 shows a standard structure of an ISFET, wherein 31 denotes the drain, 32 the source, 23 the substrate, 25 an insulating arrangement, 26 the contacts, 27 a reference electrode and 28 the solution located in a container 21 become. Mounted on the gate 1 is an electrode arrangement according to the invention, wherein the electrode 2, the layer 4 arranged on the latter and the membrane 9 can be seen. The electrode 2 and the membrane 4 are bounded by an insulating layer 3, which of a cover or Case 30 is contacted to prevent fluid leakage.

The corresponding measured values ​​are taken from the electrode arrangement by contact lines, not shown, and supplied to an evaluation device.

11 shows an arrangement in which two electrode arrangements 21 according to the invention and a further sensor, eg temperature sensor, are arranged at the front end of a catheter 18, which comprises a perfusion opening 16 and corresponding contact lines 2a leading to an evaluation unit 20.

12 shows the installation of two electrode arrangements 21 according to the invention in a flow channel 17, the electrode arrangement being fixed by means of a potting compound 20 to the flow channel 17.

The area dimensions of an electrode arrangement according to the invention are advantageously 40 × 40 μm² up to one mm², The thickness of metal layers (layers 2,4) is about 50-150 nm, the thickness of the salt layers (layers 5,6) about 0,5-3 μm), the thickness of the insulating layers about 1-3 μm, the thickness of the membrane about 30 to 100 um.