DE10164429A1 - Instrument for measurement of enzyme activity in a human or animal gullet or intestine comprises a probe body with sensor substrates which react with the specific enzyme and changes in the electrical or optical characteristics are measured - Google Patents

Abstract

Instrument to measure enzyme activity in a human or animal gullet and intestine, comprises a probe body (1) fitted with one or more sensor modules. The sensor module has a substrate (5) which reacts with the enzyme to be measured, as a biological reaction which alters the electrical or optical characteristics of the sensor module, by a change which can be measured. Instrument to measure enzyme activity in a human or animal gullet and intestinal channel, comprises a probe body (1) fitted with one or more sensor modules. The sensor module has a substrate (5) which reacts with the enzyme to be measured, as a biological reaction which alters the electrical or optical characteristics of the sensor module, by a change which can be measured. A degrading of the sensor substrate changes its electrical impedance, which can be measured and evaluated by the resistance and/or capacity and/or phase shift. An optical change varies its optical transparency. The probe has a pH monitor.

Description

The invention relates to a device for measurement of enzymatic components in the esophagus and in the Human or animal intestinal tract.

State of the art

A variety of medical examinations have been carried out in the recent years showed that the measurement of enzymatic Constituents in the esophagus and intestinal tract of great importance.

With diseases such as B. the so-called Barrett's esophagus according to the current state of science, it can be assumed that the cause of the changes in the mucosa in look for this area by reflux from the small intestine is. For years, reflux in the esophagus has only been known as reflux viewed from the stomach and the related standing acid exposure of the esophageal mucosa as the cause seen for all diseases at this point. The However, recent studies also describe one Reflux from the small intestine. In a work by Fein et. Al. (Fiberoptic Technique for 24-Hour Bile Reflux Monitoring, Digestive Deseases and Sciences, Vol. 41, No. 1, January 1996) this duodenogastric reflux is described. It has demonstrated a correlation between duodenogastric Reflux and the appearance of Barrett's esophagus (Wickbom et al., On the corrosive properties of bile and pancreatic juice on living tissue, Arch. Surg. 1974; 108: 680-684 and Pera et al., Epithelial cell hyperproliferation after biliopancreatic reflux into the esophagus of rats, Ann. Thorac. Surg. 1998; 65: 779-786).

As a measurement method for duodenogastric reflux only pH measurement and bilirubin detection in one continuous measurement method is not available sufficient to expose pancreatic enzymes to the Evidence of esophageal mucosa. With reflux from the Duodenum in the stomach can be assumed that the pH Increases in stomach value. This has been described several times. finds under these circumstances, reflux of pancreatic enzymes in the Stomach instead, there is a good chance that Enzymes maintain their aggressiveness. Now takes place further reflux into the esophagus, this is with a change connected on the mucosa and subsequently arises with high Probability the observed change that is finally to diseases such as B. can lead the Barrett's esophagus.

The mere detection of pH changes and bilirubin Concentrations are not enough to make a statement as both Effects initially not as the cause of the tissue changes come into question. Direct evidence of the Presence of pancreatic enzymes in the esophagus.

There is currently no direct and continuous detection of pancreatic enzymes in the esophagus. Indirect methods are currently available for the investigation, which are used to detect duodenogastric and consequently duodenoesophageal reflux, i.e. pH measurement and bilirubin monitoring (Bechi et al., Long Term ambulatory enterogastric reflux monitoring - validation of a new fibreoptic technique, Dig. Dis. Sci. 38: 1297-1306, 1993; Emde et al. Technical aspects of intraluminal pH-metry in man: Current status and recommendations, Gut 28 : 1177-1188, 1987).

In pH monitoring, a glass or antimony probe is used 24 h recording of pH values in the stomach and / or esophagus carried out. Measured values are usually every 5 seconds won.

In the bilirubin measurement, the presence of bilirubin is detected using a fiber-optic sensor. Measurements of several hours are also carried out here, with sampling rates of generally 5 seconds.

Both methods describe reflux, but not that Quality of its content. To detect the pancreatic enzymes in the To date, only one sample of refluxate has been used is then examined in the laboratory. Disadvantages are discontinuous time monitoring, loading of Patient and staff through sampling and the at the same time very high financial expenditure. Another disadvantage is the time discrepancy between sampling and Laboratory result (Hostein et al., Intragastric pH monitoring is not suitable for diagnosis of duodenogastric reflux, Dig. Dis. Sci. 36: 1341-1343, 1991).

Object of the invention

Derived from this state of the art, it is the task of Invention to develop a device based on safe, however also simple way of measuring enzymes in the esophagus and intestinal tract of humans or animals allowed. The device should be used as a single part and continuous measurement over a longer period of time enable.

This object is achieved by the features of Device according to claim 1 solved, the associated Subclaims show further advantageous embodiments of the Invention.

According to the device according to the invention, a Probe into the human esophagus or intestinal tract or animal introduced. The probe consists of one Probe body and one or more sensor modules that form a substrate contain, which is specific with the enzyme to be measured react. The course of the biochemical reaction is hereby designed in such a way that, through the biochemical reaction conditional change on the substrate, to an electrical or leads optically measurable change in the sensor module.

The sensor module is incorporated in the probe body is in contact with at least one surface the body fluid of the esophagus or Intestinal tract. The sensor module contains on the surface or in a depression at least one sensory element, which from an electrically conductive or optically transparent Material is made with a layer of enzyme substrate is covered. The substrate is advantageously located in a recess that z. B. cylindrical or conical can be trained.

Depending on the measurement method selected, the sensor module can be designed differently. A particularly simple one Design is the coupling of the biochemical reaction with a electrical impedance measurement. This is the effect used that in the biochemical reaction of the substrate with the enzyme undergoes a structural change in the substrate, leading to a change in the electrical conductivity of the Substrate or leads to a change in capacity. Both sizes can be measured using suitable electronics.

Since water or aqueous ionic solutions, as in the Body fluids are present, a relatively high Have dielectric constant and also the electrical Conductively changes little during substrate conversion, one can alternatively to increase the sensitivity with the substrate Additives that lead to an increase in Lead sensitivity. These additives have to be body-friendly because they are released when the substrate is dissolved. They are therefore advantageously made of carbon, e.g. B. finely powdered activated carbon or graphite-coated Glass beads. By dissolving the substrate Enzyme attack significantly changes the impedance of the substrate, so that the impedance change with relatively little electronic Effort can be measured.

The probe can be constructed in the form of a catheter. In this case the electrodes are supplied with AC voltage as also the signal transmission via a cable to an outside body device, which the necessary Electronics contains and also the representation of the measured values allows.

Alternatively, the necessary electronics together with one Battery that ensures a power supply in the probe be housed. In this case the probe can Wander the intestinal tract naturally Measurement results transmitted by radio to the outside, where the evaluation in one device. This way, enzyme profiles can be obtained via the intestinal tract.

If you choose an optical evaluation method, it serves as the substrate as an optical filter, the transmission of which depends on the structure depends on the substrate. In this case, too Effect by adding optically absorbing substances, such as z. B. coal or physiologically safe dyes Enhance measurement effect. When implementing the substrate these substances are released and the transmission over the distance increased. Technically, this can be done easily Way by measuring the transmission over one with the Cuvette filled with substrate mixture, one on one side Spotlights, e.g. B. an LED, and on the other side one the irradiated wavelength contains a specific detector, realize. Due to their small size, LED and Detector together with a preamplifier electronics directly in the Probe. The the necessary electrical energy and the measured values an evaluation and display device can be passed on. The However, the optical path can also have an optically conductive one Fiber take place, e.g. B. over two strands, one strand being the undamped signal and the other strand the signal transfers. In this case, the light source and detector are located outside the probe in the evaluation or display device. To this In this way, particularly compact designs can be achieved.

Different sensory can be on the sensor module Elements can be applied. These can differ in the type of Differentiate substrates and thus against different Be sensitive to enzymes. In this way, different Enzymes are measured. Even the geometry of the sensory Elements can differ to be different To answer questions, e.g. B. when an enzyme in different regions to be measured and / or different activities are expected, e.g. B. due different concentrations or activities through a pH influence on the activity of the enzyme. to more precise determination of these influences and also for the purpose of extraction Further information can be found in the sensor module using a pH probe usual design can be integrated.

Progress in the development of new electronic Components allow very little measurement and analysis Streams. Therefore, the sensor module with the sensory elements z. B. in microstructured form made of silicon become. By means of an etching process, the required Wells are generated and by galvanic or Vacuum coating the corresponding electronic conductors as well Electrode surfaces are applied. The sensor module can then potted in a case to be both smooth To achieve areas as well as an electrolyte access to the electronic conductors or a preamplifier prevent. These procedures allow for a small size be implemented, resulting in a very low patient burden leads during the duration of the measurement. In addition, by extensive automation, the production is comparatively inexpensive respectively.

Examples

Fig. 1 carrier in catheter design with a sensory element

The function of the device is explained in more detail below using an example for measuring trypsin. A probe ( 1 ) with cable ( 2 ) made of body-compatible material has a recess ( 3 ) on the side, with two electrodes ( 4 ) made of stainless steel, which are incorporated in the plastic and coated with gold. In the recess between the electrodes there is a mixture ( 5 ) of a protein and carbon particles sensitive to trypsin. The electrodes each have an electrical contact ( 6 ) on the back, which leads through the probe to a cable that is firmly connected to the probe.

The probe can be inserted into the esophagus using the cable. The cable has a plug ( 7 ) at the end, which is connected to an electronic evaluation unit. The evaluation unit applies a sinusoidal AC voltage of a fixed frequency to the electrodes in the sensor module and measures the electrical current flowing through the electrodes. The current flowing across the electrodes is a function of the electrode areas, the resistivity of the substrate mixture, the capacity of the substrate mixture, the AC frequency and the temperature. As long as no trypsin changes the substrate mixture, all parameters are constant, therefore the current flowing through the substrate mixture will be constant. In the presence of trypsin, the structure of the substrate mixture is changed due to the biochemical breakdown of the protein. This structural change brings about an increasing spatial separation of the carbon particles, thus a change in the electrical resistance and also in the capacitance of the substrate mixture. High concentrations of trypsin can lead to the complete dissolution of the substrate mixture. Both the electrical ohmic resistance and the change in capacitance of the substrate mixture can be used as a measured variable, the time course of the change in the measured variable being proportional to the activity of trypsin present on the sensor surface. REFERENCE NUMERALS 1 probe
2 cables
3 recess
4 electrodes
5 protein and carbon particles
6 electrical contact
7 plugs

Claims (8)

1. Device for measuring the activity of enzymes in the esophagus and intestinal tract of humans or animals by means of a probe, consisting of a probe body and one or more sensor modules contained in the probe body, characterized in that the sensor module contains a substrate which with the measuring enzyme reacts, this biochemical reaction leads to a change in the electrical or optical property of the sensor module and this change is measured. 2. Device according to claim 1, characterized in that by degrading the substrate in the sensor module electrical impedance change is generated with the degradation of the substrate correlated, this change in impedance measured and in terms of resistance and / or capacitance and / or phase shift is evaluated. 3. Device according to claim 1, characterized in that by removing the substrate in the sensor module optical permeability of a route is changed and measured this change in optical transmittance becomes. 4. Apparatus according to claim 1, 2 or 3 thereby characterized that the sensor modules are different Contain substrates and thus several enzymes at the same time can be measured. 5. Apparatus according to claim 1, 2 or 3 thereby characterized in that the sensor modules are a substrate contain different processing and the type of Processing the reaction rate of the substrate with the Enzyme affects. 6. The device according to claim 1 to 5, characterized in that the enzyme to be measured is trypsin and a simple one Protein serves as a substrate. 7. The device according to claim 1 to 6, characterized in that the probe additionally has one or more pH sensors contains for measuring the pH value. 8. The device according to claim 1 to 6, characterized in that the probe has electronics for signal evaluation contains and by means of the telemetric principle Radio information to someone outside the body Evaluation and display unit are forwarded.