This application is a divisional application of, and claims the benefit of priority under 35 U.S.C. §120 from, pending application Ser. No. 10/855,406 filed May 28, 2004 which claims priority under 35 U.S.C. §119 on German patent application number DE 103 24 600.2 filed May 30, 2003, the entire contents of each reference are hereby incorporated herein by reference.
The invention generally relates to a method for detecting at least one substance in a metabolic process of a living being and a device for carrying out the method.
There are known devices for measuring the variation over time of the concentration of a metabolic parameter, in particular portable sensor devices. These can include, for example, blood glucose measuring devices or devices for measuring the oxygen saturation of the hemoglobin. Specific glucose or hemoglobin dioxide sensors measure the target substance directly.
For example, DE 195 40 456 A1 also discloses an artificial pancreas, including a glucose sensor based on evaluation of a physical parameter of blood, an insulin reservoir, an insulin dispensing device and a microprocessor as a controller. The glucose sensor determines the glucose concentration in the blood virtually continuously and causes the insulin dispensing device to dispense insulin from the insulin reservoir according to requirements, i.e. in dependence on the glucose concentration.
In this case, the artificial pancreas can be fully implanted or can be arranged externally on the patient, the glucose sensor lying for example in a vessel of the patient, while the insulin dispensing takes place subcutaneously. The glucose sensor thereby determines the blood glucose concentration and its dynamics, that is to say the variation over time, virtually continuously and passes this information on to the controller.
An object of an embodiment of the invention is to provide an improved method for detecting at least one substance in a metabolic process of a living being and an associated device with which it is possible inter alia also to detect a difficulty detectable substance in a living being.
To monitor the variation over time of a metabolic process, a molecular, in particular biomolecular, contrast agent is administered. For example, it is injected into the body of a living being, taken orally, etc. The agent bonds specifically to a metabolic component, for example a transforming molecule, in particular an enzyme, or a metabolic product, for example a substrate, of the metabolic chain of interest. Or it is activated into a signaling state by way of a biochemical reaction with this metabolic component or metabolic product. As a result, metabolic components or metabolic products which it is not possible to detect directly, in particular through a skin of the living being, at all, or only with great effort, are detectable. Thus, the rate of a metabolic process may be calculated based on results of the detection wherein an unknown (or indirectly detectable) parameter may be determined based on a known (or directly detectable) parameter.
In this case, the specifically bonded molecule or the activated contrast agent can be traced by use of a detector. The detector may be integrated in a corresponding device which can be carried over a relatively long period of time on or in the body of the living being. The device optionally has a device/method for signal evaluation and/or signal transmission.
In this respect, there are numerous known contrast agents which, by way of molecular engineering, bond highly specifically to target molecules, for example proteins. Subsequently, by use of a signaling substance coupled to them, they can emit a signal which can be measured outside the body. As such, the presence of the target molecules, and if appropriate their concentration, can be detected.
Examples of such contrast agents are described in U.S. Pat. No. 6,083,486. These include a number of functional components, the alternatives of which are listed in column 1, line 61 to column 3, line 29 of U.S. Pat. No. 6,083,486.
According to the prior art, these biomolecular contrast agents, in particular fluorescent contrast agents, are used for optical imaging and in pharmaceutical research with small animals, for example mice. This primarily involves presenting the spatial distribution of a target molecule in the body, which serves for example for the diagnosis and localization of a tumor. Since, however, such contrast agents can be used for example to detect proteins, DNA and/or RNA segments, which are the starting point or reagent of a metabolic process chain, such contrast agents are also suitable for highly specifically characterizing a metabolic process of interest.
Biomolecular contrast agents such as are described in the aforementioned U.S. Pat. No. 6,083,486, may also be designed in such a way that a distinction can be made between active and inactive process variants or that the activity of enzymes themselves or of decomposition products produced by the enzymes can be measured. According to an embodiment of the invention, the transformation of a reagent product or a decomposition product that is characteristic of a biological metabolic process can thereby be measured in a highly specific way, and consequently the metabolic rate can be concluded.
In this case, the concentration of a molecule from a metabolic chain can be measured over a relatively long period of time. This allows answers to be found to the medically motivated questions of whether a specific metabolic process, for example a metabolic process which is characteristic of a tumor, or a decomposition process, is taking place at all for example in the liver. It further allows one to determine at what time intervals, expressed in minutes, hours or days, the metabolic process is taking place; with which intensity the metabolic process is taking place; and/or whether the intensity is currently increasing, decreasing or remaining constant.
For detecting the contrast agent, it may in this case be assumed that the location at which the concentration of the metabolic marker of interest is present in a meaningful concentration is known. For example, many metabolic markers are transported in a detectable concentration in the bloodstream and are consequently measurable at any point of the cardiovascular system. Other suitable measuring locations may be on the surface of the body directly over organs of the body, for example the liver, the kidneys or lymph nodes, or directly over lesions, for example tumors and wounds from operations, etc.
A portable device which can be carried on the body and contains a detector which can measure the signals emitted by the molecular contrast agent over the course of time, for example as a fluorescence signal, magnetic field or radioactive radiation, and can record them over time, is placed at this location identified as suitable. For example with respect to the contrast agents of U.S. Pat. No. 6,083,486, the wavelengths of which are specified in Table 1 of U.S. Pat. No. 6,083,486, the detector must be suitable for detecting the wavelengths emitted by the fluorescent contrast agent. In this case, selective detection is carried out in an advantageous way using an upstream optical filter.
The present invention will become more fully understood from the detailed description of preferred exemplary embodiments given hereinbelow and the accompanying drawing, which is given by way of illustration only and thus are not limitative of the present invention, and wherein:
In a further embodiment of the invention, the contrast agent is designed such that it can be enriched in the spatial vicinity of the detector unit 110 by way of an enriching unit 120 that is integrated in the device 100. This can be achieved for example by the contrast agent having magnetic properties, for example including iron oxide particles, and the enriching unit 120 including a magnet, so that the magnetic molecules of the contrast agent are drawn toward the magnet or, when they are transported through the system of vessels, partly immobilized in the vicinity of the magnet in the blood vessel. The magnet may be designed as an electromagnet 125, so that the immobilization of the molecules can be switched on and off. By such a procedure, the molecules can be enriched in the vicinity of the detector unit 110 and consequently an intensified measurement signal can be obtained.
The device 100 also include a memory unit 130, in which the variation over time of the measurement signal recorded by the detector unit 110 is stored. Furthermore, at least one interface unit 150 is provided, for the wireless and/or cable-bound transmission of the signals to a receiver for the evaluation and/or presentation of the signals. In one embodiment, the measurement signal can also be transmitted to a receiver without intermediate storage, by way of wireless transmission.
The device 100 also includes a display unit 160 for the alphanumeric and/or graphic display of the intensity of the metabolic process and/or for indicating the trend of the metabolic process in the sense of increasing, decreasing or remaining constant. It further includes an alarm transmitter unit 170, which becomes active if the signal goes above or below a preset threshold value of the measurement signal. Finally, the device 100 also includes an input unit 165, for example a keypad, for setting device options or entering data, for example a threshold value; and a processor unit 140 for evaluating the measurement data and/or a dosing unit 175 for medicaments.
In one embodiment, at least the detector unit 110 and/or the processor unit 140 are in this case set up in such a way that only the presence or absence of the measurement signal or of the measurement signal lying above the threshold value of a background activity or a background noise is detected and used to conclude the presence or absence of the metabolic process being observed. In another embodiment, in which it is assumed that the intensity of the measured signal is proportional to the concentration of the component of the contrast agent that highlights the target molecules, consequently proportional to the concentration of the target molecule and to the intensity of the metabolic process, the detector unit 110 in particular is set up for intensity-sensitive detection.
Furthermore, in one embodiment the device 100 is set up in such a way that a point in time at which the contrast agent is delivered can be entered into the device 100 and stored, in order to be able to take this point in time into account in the evaluation and, if appropriate, presentation of the signals. Similarly, in one embodiment the amount of the contrast agent administered can be entered.
Furthermore, the device 100 includes a reservoir unit 185 for the contrast agent and an injection unit 180 for the contrast agent, by which parts of the contrast agent located in the reservoir unit 185 can be injected into the living being in a dosed amount on command or at time intervals which can be preset.
Finally,
In embodiments of the invention, the configurations of the devices 102 to 108 which can be carried on the body do not comprise all the units 110 to 185 described with respect to
Exemplary embodiments being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.
Number | Date | Country | Kind |
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10324600.2 | May 2003 | DE | national |
Number | Date | Country | |
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Parent | 10855406 | May 2004 | US |
Child | 12010246 | Jan 2008 | US |