DE102017116847A1 - Detection of a valve state of a sample separator by means of acting on the flow path of the valve signal - Google Patents

Abstract

A detection device (100) for detecting information indicative of a condition of a fluidic valve (95) of a sample separation device (10), the detection device (100) comprising stimulation means (102) for emitting a stimulation signal into a fluidic flow path (104) of the valve (95 ), detecting means (106) for detecting a response resulting from the stimulus signal indicative of a fluid's ability to flow through the fluidic flow path (104) of the valve (95) in the current state of the fluidic valve (95), and determining means (108) for determining the state indicative information based on the response.

Description

TECHNICAL BACKGROUND

 The present invention relates to a detection device, a valve assembly, a sample separation device, a method for detecting information indicative of a state of a fluidic valve of a sample separation device, and a use.

In an HPLC, a liquid (mobile phase) is typically run at a very precisely controlled flow rate (for example in the range of microliters to milliliters per minute) and at a high pressure (typically 20 to 1000 bar and beyond, currently up to 2000 bar). , in which the compressibility of the liquid can be felt, by a so-called stationary phase (for example, in a chromatographic column), moved to separate individual components of a sample liquid introduced into the mobile phase from each other. Such an HPLC system is known, for example from the EP 0,309,596 B1 same Applicant, Agilent Technologies, Inc.

 The accurate and reproducible control of a sample separator for generating a properly definable flow of a mobile phase requires exact knowledge of each state of a respective fluidic valve. This is traditionally difficult with sample separation equipment and limits the reproducibility of measurement results on HPLC equipment as well as other sample separation equipment.

EPIPHANY

 It is an object of the invention to operate a sample separation device having at least one fluidic valve with high reproducibility and accuracy. The object is achieved by means of the independent claims. Further embodiments are shown in the dependent claims.

 According to an exemplary embodiment of the present invention, a detection device (for example, partially configured as a processor) for detecting a state (eg, a check valve opening or closing state or a switching state of a rotor valve or a multi-way valve) of a fluidic valve (in particular a passive valve or an active valve) of a sample separation device (in particular a chromatographic sample separation device) indicative information, wherein the detection device comprises a stimulus device for emitting a stimulation signal in a fluidic flow path of the valve, a detection device for detecting a response resulting from the stimulation signal (in particular a response signal ) indicative of a capability of fluid (in particular a liquid and / or a gas or a substance in the supercritical state, optionally comprising solid particles) ativ is to flow through the fluidic valve in the current state of the fluidic valve, and has detection means for determining the state indicative information based on the response.

 According to another exemplary embodiment, there is provided a valve assembly for a sample separator having a fluidic valve with a fluidic flow path and a detection device having the features described above for detecting information indicative of a condition of the fluidic valve.

 According to another exemplary embodiment, a sample separator is provided for separating a fluidic sample (e.g., having multiple fractions), the sample separator having a fluid driver configured to drive a mobile phase and the fluid sample received therein, a sample separator (e.g., a chromatographic probe) Separation column) for separating the mobile phase in the fluidic sample, a fluidic valve with a - depending on a state of the fluidic valve - at least partially open or closed flow path to be flowed through by the mobile phase and / or the fluidic sample as a fluid when the valve is at least partially open, and has a detection device with the features described above for detecting information indicative of a state of the fluidic valve.

 According to yet another exemplary embodiment, there is provided a method of detecting indicia indicative of a condition of a fluidic valve of a sample separator, the method comprising sending a stimulus signal into a fluidic flow path of the valve, detecting a response resulting from the stimulus signal indicative of an ability of fluid is indicative of flowing through the fluidic valve in the current state (in particular, switching state or opening state) of the fluidic valve, and determining the state indicative information based on the response.

According to a further exemplary embodiment, information indicative of a condition of a fluidic valve of a sample separation device detected by means of a detection device with the features described above is provided for controlling the sample separation device, in particular for controlling a fluid drive of the sample separation device used.

 According to an exemplary embodiment of the invention, a sensor architecture is provided for detecting a condition of a fluid valve of a sample separator based on adapting a pacing signal to a valve flow path (at least partially open or closed depending on the valve state) (specifically, a flow path of the valve) Valve is exposed to a stimulus signal) and that the response - for example in the form of a response signal - the consisting of valve, including detection device, fluid and connecting lines system is detected on the stimulus signal. Depending on the degree of opening or state of the valve, the pacing signal may pass through or into the flow path to a different degree and / or be attenuated, distorted, converted, or altered to a different degree. In this way, even dynamic information about the temporal change of the state of the valve can be detected in a simple and precise manner. The degree of passing or not passing the stimulus signal through the flow path or intrusion into the flow path is detected and evaluated. The information about the valve state or its temporal change can be used, for example, for a precise control of the solvent composition in the sample separation device and finally for a reproducible, correct and precise operation thereof. A frequently inaccurate, difficult and expensive direct detection of variables such as pressure or flow rate in the immediate vicinity of the valve to determine a valve state can be dispensable.

 In addition, additional embodiments of the detection device, the valve assembly, the sample separation device and the method will be described.

 According to one embodiment, the determining means may be arranged to dynamically determine the state indicative information over a time course. For example, it can be determined how long a valve was open between two closing phases or how long a valve was closed between two opening phases. If the state of the valve is monitored over a time interval, for example, a process for proportioning solvents to form a solvent composition can be monitored and possibly corrected, in particular approximately in real time. This makes it possible to control with high precision which course, for example, has a gradient profile in the context of a chromatographic separation method exactly. This allows precise control of a sample separator.

• A) zur Steuerung und/oder Regelung der Parameter eingesetzt werden kann, ausgewählt aus einer Gruppe bestehend aus: – einer Lösungsmittelzusammensetzung (zum Beispiel eine zeitlich veränderliche Zusammensetzung aus zwei oder mehr Lösungsmitteln, beispielsweise einem organischen Lösungsmittel und einem anorganischen Lösungsmittel), insbesondere die Genauigkeit einer Lösungsmittelzusammensetzung, des Fluids in dem Probentrenngerät; die genaue Kenntnis, Steuerung, Regelung und/oder Einhaltung der Lösungsmittelzusammensetzung bei einem chromatografischen Trennverfahren erhöht die Richtigkeit und Präzision der Trennung – einer Flussrate (insbesondere eine Volumenflussrate, d.h. fließendes Fluidvolumen pro Zeit, oder eine Massenflussrate, d.h. fließende Fluidmasse pro Zeit) des Fluids in dem Probentrenngerät; die Kenntnis, Steuerung, Regelung und/oder Einhaltung der Flussrate erlaubt eine präzisere Steuerung einer Menge von gefördertem Fluid
• und/oder B) die – Druckverhältnisse, insbesondere einen Druckwert oder ein Verhältnis zweier Druckwerte zueinander (insbesondere in Form der Information, ob der eine Druckwert größer als, kleiner als oder gleich wie der andere Druckwert ist), in dem Probentrenngerät beschreibt; Druckwerte an bestimmten Positionen in einem fluidischen Probentrenngerät sind herkömmlich nur sehr schwierig erfassbar; durch ein dynamisches Erfassen eines Zustands eines Fluidventils kann auf bestimmte wichtige Druckverhältnisse präzise und einfach geschlossen werden; und/oder – Flussverhältnisse, insbesondere Vorhandensein/Nichtvorhandensein eines Flusses in dem Durchflusspfad, beschreibt. – Steuerinformationen zum Steuern des Probentrenngeräts, insbesondere eines Fluidantriebs des Probentrenngeräts; insbesondere kann die detektierte Information also zum Steuern des Probentrenngeräts oder Regeln seines Betriebs verwendet werden, weiter insbesondere zum Steuern oder Korrigieren einer vom Gerät hergestellten Lösungsmittelzusammensetzung oder einer Flussrate

According to one exemplary embodiment, the determination device can be set up to derive at least one piece of information based on the dynamically determined time profile

• A) can be used for controlling and / or regulating the parameters selected from a group consisting of: - a solvent composition (for example a time-varying composition of two or more solvents, for example an organic solvent and an inorganic solvent), in particular the accuracy a solvent composition, the fluid in the sample separator; The precise knowledge, control, and / or compliance of the solvent composition in a chromatographic separation process increases the accuracy and precision of the separation - a flow rate (especially volume flow rate, ie, fluid volume per unit time, or mass flow rate, ie, fluid mass per unit time) of the fluid in the sample separator; the knowledge, control, regulation and / or compliance with the flow rate allows a more precise control of a quantity of fluid delivered
• and / or B) the pressure ratios, in particular a pressure value or a ratio of two pressure values to each other (in particular in the form of information as to whether one pressure value is greater than, less than or equal to the other pressure value) in the sample separation device; Pressure values at certain positions in a fluidic sample separation device are conventionally very difficult to detect; by dynamically detecting a condition of a fluid valve, it is possible to precisely and easily close certain important pressure conditions; and / or flow conditions, in particular presence / absence of flow in the flow path. Control information for controlling the sample separation device, in particular a fluid drive of the sample separation device; In particular, the detected information can thus be used to control the sample separator or to control its operation, more particularly to control or correct a solvent composition or flow rate produced by the device

The parameters "solvent composition" and "flow rate" are the result of doing or operating the valve. For example, their variation or their deviations can be determined. In particular, it is possible to do the To detect and intervene in order to make the expected as a result of the valve function values of said parameters as accurate and correct. Advantageously, it may be possible by the opening and / or closing information, to control the device more precise or regulate, so that the listed target values are taken very precisely.

 According to one embodiment, the stimulation means may be arranged to emit an electrical stimulation signal (for example an electric current or a constant or oscillating electric field) into the fluidic flow path of the valve for interaction with or through the fluid. Coupling of an electrical signal as a stimulus signal reliably allows the distinction between an open and a closed state of the valve when the response of the system to the electrical stimulus signal is detected.

 According to one embodiment, the sensing means may be arranged to discriminate an electrical response between the case when the fluidic valve is in an at least partially open state and the electrical stimulation signal is passed through the fluidic flow path of the valve by means of electrically conductive fluid and when the fluidic valve is in a closed state. The detection device may e.g. be positioned or set up so that it is susceptible to the stimulus signal only in the valve open state.

• – einer Antwort infolge eines Transports von elektrischem Strom durch ein elektrisch leitfähiges Fluid durch den Durchflusspfad hindurch. Wenn das Fluid elektrisch leitfähig ist, leitet es ein elektrisches Stimuliersignal im offenen Ventilzustand durch den fluidischen Durchflusspfad des Ventils. Im Unterschied hierzu leitet es ein elektrisches Stimuliersignal im geschlossenen Ventilzustand durch den fluidischen Durchflusspfad des Ventils nicht, wenn die entsprechenden Komponenten des Ventils elektrisch isolierend ausgestaltet sind. Auf diese Weise ist durch eine elektrische Messung der Antwort auf das elektrische Stimuliersignal der Zustand des Ventils erkennbar oder detektierbar, vorwiegend oder ausschließlich wenn das Fluid elektrisch leitfähig ist.
• – einer Antwort infolge eines Polarisationsverhaltens eines dielektrischen Fluids bei einem Anlegen einer elektrischen Spannung. Wenn das Fluid dielektrisch ist (insbesondere eine hohe Dielektrizitätskonstante von zum Beispiel 20 oder mehr hat), wirkt es bei Anlegen eines elektrischen Wechselsignals wie ein Dielektrikum eines Kondensators etwa zwischen zwei Kondensatorplatten in Form elektrischer Anschlüsse von Stimuliereinrichtung und Erfasseinrichtung stromaufwärts und stromabwärts des Ventils. Dieser Kondensator hat unterschiedliche kapazitive Eigenschaften, wenn der Durchflusspfad des Ventils geöffnet oder geschlossen ist. Auf diese Weise ist durch eine elektrische Messung der Antwort auf das elektrische Stimuliersignal der Zustand des Ventils ermittelbar, wenn das Fluid dielektrische Eigenschaften hat.
• – einer Antwort auf ein wechselndes oder alternierendes elektrisches Stimuliersignal infolge eines kapazitiven oder reaktiven elektrischen Stroms im fluidischen Durchflusspfad durch ein dielektrisches Fluid

In particular, the capture device may be configured to capture at least one of a group consisting of:

• A response due to transport of electric current through an electrically conductive fluid through the flow path. When the fluid is electrically conductive, it conducts an electrical stimulus signal in the valve open state through the fluidic flow path of the valve. In contrast, it does not conduct an electrical stimulus signal in the closed valve state through the fluidic flow path of the valve when the corresponding components of the valve are made electrically insulating. In this way, the state of the valve can be detected or detected by an electrical measurement of the response to the electrical stimulation signal, predominantly or exclusively when the fluid is electrically conductive.
• A response due to a polarization behavior of a dielectric fluid upon application of an electrical voltage. When the fluid is dielectric (in particular, has a high dielectric constant of, for example, 20 or more), it acts like a dielectric of a capacitor between two capacitor plates in the form of electrical connections of stimulator and detector upstream and downstream of the valve. This capacitor has different capacitive characteristics when the flow path of the valve is open or closed. In this way, by an electrical measurement of the response to the electrical stimulus signal, the state of the valve can be determined when the fluid has dielectric properties.
• A response to a changing or alternating electrical stimulation signal due to a capacitive or reactive electric current in the fluidic flow path through a dielectric fluid

 According to an exemplary embodiment, the stimulation device may comprise a stimulation electrode (for example in a fluid channel connected to the valve) for emitting the stimulation signal upstream of the fluidic valve (in particular a valve seat of the valve) and the detection device a detection electrode (for example in an other fluid channel connected to the valve ) for detecting the response downstream of the fluidic valve (in particular a valve seat of the valve). According to another embodiment, the stimulation means may comprise a stimulation electrode (for example in a fluid channel connected to the valve) for emitting the stimulation signal downstream of the fluidic valve (in particular a valve seat of the valve) and the detection means a detection electrode (for example in another connected to the valve Fluid channel) for detecting the response upstream of the fluidic valve (in particular a valve seat of the valve). Such electrodes may, for example, be attached, for example vapor deposited, to an inner surface of a fluid-carrying capillary or other fluid conduit or to the valve itself. Such electrodes do not affect the fluidic function of the valve and its fluidic ports, yet allow precise determination of the condition of the valve. In particular, a stimulation electrode and a detection electrode or a functionally combined electrode, in particular as a single electrode on one side of the valve and a ground electrode or a current sink (also as electrically conductive component of the chromatography device) can be mounted on the other side of the valve, wherein a reduction the response signal for opening the valve may be indicative. In particular, using only one electrode, e.g. Voltage can be used as a stimulus signal and current as a response signal, or; vice versa; Current as stimulus signal and voltage as response signal.

According to one embodiment, it is also possible to detect the valve state with only one electrode, for example when there is a current sink on the opposite side. Then, for example, at this one electrode can be stimulated with an electrical voltage, for example, and the current can be detected.

 According to an exemplary embodiment, the stimulation device can be set up to emit an electrical alternating current, voltage or field signal as a stimulation signal. The oscillating or generally alternating electrical signal can in particular be provided with a frequency of at least 10 Hz, more particularly with a frequency of at least 1000 Hz, preferably with a frequency of at least 10,000 Hz. The use of a preferably high-frequency electrical signal as a stimulation signal in an electrical determination of the valve state is particularly preferred in view of the specific conditions in a sample separation device, since the mobile phase or the fluidic sample by an alternating electrical signal neither the unwanted effect of electromigration nor that of electrolysis is exposed. As a result, when using an electrical stimulation signal sample separation remains undisturbed, the chemical nature of the mobile phase unchanged and spared the parts of the analyzer and the stimulation and detection device from electrocorrosion.

 According to one exemplary embodiment, the stimulation device can be set up a stimulus signal of an electromagnetic nature, in particular an optical stimulation signal (ie a stimulation signal in the form of electromagnetic radiation, in particular in the visible wavelength range) in the fluidic flow path of the valve for propagating along a transparent path for the electromagnetic radiation, in particular optically transparent, emit fluids. Also, a stimulating signal in the form of electromagnetic waves does not affect a flow of fluid nor the (subsequent) process of separating a fluidic sample in the sample separating device. The coupling of the stimulation signal in the form of the electromagnetic radiation is preferably carried out in the fluid itself, so that propagates the electromagnetic radiation to the fluidic flow path. If the current state of the valve permits (i.e., when the valve is fully or partially open), the electromagnetic stimulus signal propagates through the fluidic flow path to the other valve side where it may be detected as the response of the system. On the other hand, if the current state of the valve does not permit propagation of the electromagnetic stimulation signal through the fluidic passageway of the valve (i.e., if the valve is closed), electromagnetic radiation of the stimulus signal on the other valve side can not arrive and therefore can not be detected. In this way, the detected response of the system to the coupling of the electromagnetic stimulus signal is indicative of the current state of the valve.

 According to one embodiment, the detection device may be arranged or arranged to detect or detect an electromagnetic, in particular optical, response only when the fluidic valve is in an at least partially open state and the electromagnetic, in particular optical, stimulation signal by means of the for the transparent, in particular optically transparent, fluid is passed through the fluidic flow path of the valve. In the case of fluids used for (in particular chromatographic) sample separation devices, sufficient optical transparency in a relevant wavelength range (in particular in the region of visible light) is generally given without problems. This makes it possible to at least partially coincide a fluidic propagation path and a propagation path of the electromagnetic stimulation signal. Then, an intensity of the electromagnetic stimulus signal on the opposite valve side reflects the ability of the fluid to flow through the valve, thus providing a reliable indicator of the valve's currently open state.

According to an exemplary embodiment, the stimulation device may comprise an electromagnetic radiation source (in particular a light source, such as a light emitting diode) for emitting the stimulation signal upstream of the fluidic valve (in particular a valve seat of the valve) and the detection device an electromagnetic radiation detector (for example a photodiode) for detecting the Answer downstream of the fluidic valve (in particular a valve seat of the valve). According to another embodiment, the stimulation means may comprise an electromagnetic radiation source (in particular a light source, such as a light emitting diode) for emitting the stimulation signal downstream of the fluidic valve (in particular a valve seat of the valve) and the detection means detecting an electromagnetic radiation detector (for example a photodiode) the response upstream of the fluidic valve (in particular a valve seat of the valve). The electromagnetic radiation emitted by the electromagnetic radiation source can be coupled, for example, by means of a light guide (in particular an optical fiber) from the electromagnetic radiation source into the flow path in the region of the valve. Alternatively or additionally, it is downstream the valve also possible to extract a possible response in the form of a part / fraction of the emitted / introduced electromagnetic radiation in the case of an open valve by means of a light guide (in particular an optical fiber) from the flow path and fed to the electromagnetic radiation detector for detection.

 It is possible to further increase the accuracy of the detection in that the electromagnetic radiation source emits electromagnetic radiation having a predetermined modulation pattern and / or only at a certain wavelength (or only in a certain wavelength range) and the electromagnetic radiation detector extract electromagnetic radiation with this modulation pattern or only at a certain wavelength (or only in a certain wavelength range) can detect. Thereby, a differentiability between the detection of the electromagnetic stimulation signal under detection of stray light can be enhanced.

 According to an exemplary embodiment, the stimulation device may comprise an electromagnetic radiation source for emitting the stimulation signal and the detection device comprises an electromagnetic radiation detector for detecting the response, wherein the stimulation device and the detection device on the same side of the fluidic valve (in particular both upstream or both downstream of the fluidic valve (in particular a Valve seat of the valve, which can be closed by a valve body)) are arranged. For example, in response to the fluidic system responding to the initiated electromagnetic stimulus signal, electromagnetic response radiation generated in an open valve state beyond the fluidic flow path of the valve on the opposite valve side upon receipt of the stimulus signal may be detected.

 According to one embodiment, the detection device may comprise a signal converter, which is set up to convert this signal when acted upon by the stimulation signal and thereby to generate a response signal to be detected. Preferably, this response is generated by the signal converter by converting the stimulus signal into a distinct signal (eg, due to another type of signal - such as electrical stimulus signal versus electromagnetic response signal - or due to another signal property - eg, a changed frequency or wavelength). In this context, a signal converter is to be understood as meaning, in particular, a medium, a component or a device to which the stimulation signal can act in such a way that, as a result of this action, the signal converter generates a response signal whose detection allows it to be inferred Interaction between the stimulus signal and the signal converter has come. If the signal converter is arranged on the valve side, which is opposite to another valve side, on which the stimulus device is arranged, the detection of a response signal generated by the signal converter allows the conclusion that the stimulus signal could pass through the valve's flow path, hence the valve in an at least partially open state is located.

• – Fluoreszenzmaterial, einschließlich Phosphoreszenz- und Anti-Stokes-Fluoreszenzmaterial, das eingerichtet ist, bei Bestrahlung mit elektromagnetischer Strahlung als Stimuliersignal elektromagnetische Strahlung mit anderer Frequenz bzw. Wellenlänge als Antwortsignal zu erzeugen; bei einem solchen Ausführungsbeispiel erzeugt das den Signalwandler bildende elektromagnetische Lumineszenzmaterial bei Bestrahlung mit dem elektromagnetischen Stimuliersignal ein elektromagnetisches Antwortsignal einer charakteristischen Frequenz (insbesondere einer Frequenz, die kleiner als die Frequenz des Stimuliersignals ist), sodass die Detektion oder Nicht-Detektion dieses spezifischen elektromagnetischen Antwortsignals den Schluss zulässt, in welchem Zustand sich das fluidische Ventil befindet
• – Elektrolumineszenzmaterial (wobei unter Elektrolumineszenz insbesondere ein Phänomen verstanden wird, bei der ein Festkörper durch Anlegen eines insbesondere wechselnden elektrischen Feldes bzw. einer elektrischen Spannung dazu angeregt wird, elektromagnetische Strahlung, zum Beispiel in Form von Licht, zu emittieren), das eingerichtet ist, bei Beaufschlagung mit einem elektrischen Stimuliersignal (d.h. mit einem elektrischen Feld-, Strom- oder Spannungssignal) elektromagnetische Strahlung als Antwort zu erzeugen; bei einem solchen Ausführungsbeispiel erzeugt das den Signalwandler bildende Elektrolumineszenzmaterial bei Beaufschlagung mit einem elektrischen Feld, einem elektrischen Strom oder einer elektrischen Spannung als Stimuliersignal ein elektromagnetisches Antwortsignal (d.h. emittiert elektromagnetische Antwortstrahlung) einer charakteristischen Frequenz, sodass die Detektion oder Nicht-Detektion dieses spezifischen elektromagnetischen Antwortsignals den Schluss zulässt, in welchem Zustand sich das fluidische Ventil befindet, wobei die Passierbarkeit des fluidischen Pfades gleich für zwei stark unterschiedliche Signale (elektrisches Feld und Licht) vorteilhaft für die Antwortdetektion ist, was unter bestimmten Umständen die Zuverlässigkeit der Zustandserkennung erhöhen kann.

According to one embodiment, the signal converter may be selected from a group consisting of:

• - Fluorescence material, including phosphorescence and anti-Stokes fluorescent material, which is adapted to generate when irradiated with electromagnetic radiation as a stimulation signal electromagnetic radiation with a different frequency or wavelength as a response signal; In such an embodiment, the electromagnetic luminescent material forming the signal transducer generates an electromagnetic response signal of a characteristic frequency (in particular a frequency which is less than the frequency of the stimulation signal) upon irradiation with the electromagnetic stimulation signal, so that the detection or non-detection of this specific electromagnetic response signal Final allows in which state the fluidic valve is located
• Electroluminescent material (electroluminescence being understood in particular as a phenomenon in which a solid is excited by the application of a particularly alternating electric field or an electrical voltage to emit electromagnetic radiation, for example in the form of light), which is set up upon application of an electrical stimulus signal (ie, with an electric field, current or voltage signal) to generate electromagnetic radiation in response; In such an embodiment, the electroluminescent material constituting the signal converter generates an electromagnetic response signal (ie, emits electromagnetic response radiation) of a characteristic frequency upon application of an electric field, electric current, or voltage as a stimulus signal, so that the detection or non-detection of this specific electromagnetic response signal allows the conclusion in which state the fluidic valve is, wherein the passability of the fluidic path equal for two highly different signals (electric field and light) is advantageous for the response detection, which under certain circumstances can increase the reliability of the state detection.

 According to one embodiment, the signal converter may be arranged on one side of the fluidic valve, which is opposite to another side of the fluidic valve, on which other side the stimulation device and the detection device are arranged. In this way, it can be ensured that the detection of an electromagnetic response signal generated by the signal converter beyond the valve in response to the coupling of a stimulus signal on this side of the valve only in an open state of the valve, not in a closed state of the valve, is possible.

 According to one embodiment, the signal converter may be configured to generate a differentiable response from the stimulus signal. In particular, this differentiability can be achieved by means of a frequency-selective component, for example a frequency filter, the detection device or in front of the detection device. When the generation of an electromagnetic response signal by the signal converter based on. Electroluminescence or, in particular, fluorescence or phosphorescence, a response of the system may be expected as a result of the emission of a stimulus signal in the form of an emission of electromagnetic radiation of a particular wavelength or wavelength range. If a detection device (for example by equipping with a corresponding frequency filter) is configured to be able to detect electromagnetic response radiation only at this wavelength or this wavelength range, discrimination of the electromagnetic response radiation from other signals (stimulus signal, scattered radiation, etc.) is reliably enabled.

 According to one exemplary embodiment, the stimulation device can be designed to emit a substantially monochromatic electromagnetic, in particular optical, signal as a stimulation signal. The emission of a substantially monochromatic electromagnetic stimulation signal is possible, for example, by a laser, in particular a laser diode, and enables a reliable differentiation of the stimulation signal from a response by means of a frequency analysis.

 According to one embodiment, the stimulus device for emitting and the detection device for detecting a respective signal to be set up, which may be an acoustic signal (in particular an ultrasonic signal) or a heat signal (in particular a heat radiation signal or a heat conduction signal). It is thus also possible to use different other stimulus signals or responses from electrical and electromagnetic stimulation signals or responses

 According to one exemplary embodiment, the stimulation device, the detection device and the flow path of the fluidic valve can be arranged relative to one another such that the stimulation signal can only propagate in an at least partially open state of the fluidic valve from the stimulation device through the flow path to the detection device and can be detected there as an answer is. For this purpose, the propagation paths of the fluid on the one hand and the stimulation signal on the other hand, at least partially and partially matching formed. Then, detection of a stimulus signal that has passed through to the detection device allows a conclusion to be drawn about a current ability of the fluid to pass through the flow path of the valve, and thus a conclusion about the state of the valve.

 According to one embodiment, the determination device may be configured to determine whether the fluidic valve is open or closed. According to such an embodiment, it is determined qualitatively (in particular based on a yes / no logic) whether the valve is open or closed.

 According to another embodiment, the determining means may be arranged to determine to what degree the fluidic valve is opened. For example, an intensity of the propagated stimulus signal at the location of the detector or an intensity of a response signal generated in response to the stimulus signal by the fluidic system may be defined as a measure of the degree of opening (where the degree of opening is defined as or by one of the values from the list) the width of the opening gap, the free open path cross section, the flow permeability of the path (as reciprocal of the fluidic resistance) or even the flow rate, whereby the degree of opening can be either as absolute value or as relative value (approximately to 100% of the theoretically possible opening degree Clearly, the farther the fluidic valve is opened, the greater the amount of pacing signal the valve can pass through, so a quantitative analysis of the response of the system to the pacing signal can go beyond a yes / no logic to the derivative of quantitative Allow information about the opening of the valve.

According to one embodiment, the Determination device be configured to detect a transition of the fluidic valve between a closed state and an open state based on a (in particular abrupt) change in the response. In particular, the determination device can be set up, a transition of the fluidic valve from a closed state to an open state by means of a (in particular erratic) increase (or a (particular abrupt) reduction) a strength of the response and / or a transition of the fluidic valve of a open state to a closed state based on a (in particular abrupt) reduction (or a (in particular erratic) increase) to recognize a strength of the answer. However, depending on the design of the detection means, an increase in the response signal, the closing of the valve and a reduction in a magnitude of the response of the response signal may mean opening the valve. This is the case, for example, when the stimulation device and the detection device are arranged on one side of the valve, and a signal sink on the other side. For example, the transmitter and receiver may be in front of and a ground may be located behind the valve. Also, the light source and detector can be located in front of and a light absorbing part can be placed behind the valve. In this case, opening the valve would result in the loss of part of the signal and thus in the reduction of received signal strength. It has been shown that a temporal assignment of a step or a jump when switching the valve when using high-frequency stimulation signals (in particular with a frequency of at least 10,000 Hz) can be achieved particularly easily and precisely. Thus, the use of a high-frequency stimulus signal leads to a particularly good solubility of a switching time of the valve and thus when operating a Probetrenngeräts to a particularly accurate and correct handling of the fluid involved.

 According to one embodiment, the valve arrangement or the sampling device may have a control device which is set up to adapt an operation of the sample separation device based on the information indicative of the state of the fluidic valve. In particular, in this way a piston movement of a fluid drive (in one embodiment as a piston pump) of the sample separation device can be adjusted. Further, in particular, it is possible to make such an adjustment with regard to an amplitude and / or with regard to a speed and / or a timing of temporally subsequent switching operations of the fluidic valve or of another fluidic valve of the sample separating device. Thus, according to an exemplary embodiment, a device or a method can be provided in which the information obtained about the switching state of the valve for adjusting or regulating the device operation are used, in particular for adjusting the piston movement in terms of their amplitude and / or speed, the timing of temporally subsequent switching operations of the valve and / or another valve in the device.

According to one embodiment, in the valve arrangement, the fluidic valve may have at least one further fluidic flow path and the valve arrangement may have at least one further detection device with the features described above, wherein each of the detection devices is associated with a respective one of the flow paths and is adapted to detect whether fluid is present in the current one State of the fluidic valve is able to flow through the respectively associated fluidic flow path of the valve. In the case of a rotor valve, a proportioning valve or another multi-way valve, a plurality of alternative or simultaneously switchable flow paths can be provided (see for example reference signs) 29 in 2 ). In order to determine the switching state of such a valve, each of the flow paths can be assigned a detection device which detects by sending a stimulus signal in the respective flow path and detecting and evaluating the answer, if the respectively associated flow path is currently open or closed or which partial opening of the has respective flow path straight. However, the detection devices associated with the individual flow paths may have partly common units or components or elements, for example they may have a common stimulus device and separate detection devices or conversely a common detection device and separate stimuli devices (which may emit signals of different characteristics such as frequency).

 According to one embodiment, the fluidic valve of the sample separator or valve assembly may be a proportioning valve, a check valve, an injector valve, a rotor valve, a one-way valve, or a multi-way valve. A proportioning valve is used in a sample separator to produce a solvent mixture having an accurately and precisely controlled composition. The particularly dynamic determination of a state of a proportioning valve allows a precise conclusion on a solvent proportioning and thus a particularly accurate achievement of a desired solvent composition and thus a particularly correct and reproducible performance of a sample separation experiment. Check valves may, for example, be arranged at an inlet or an outlet of a piston pump or between a plurality of stages of a multi-stage piston pump and may control the fluid flow there. Rotor valves are suitable, for example, for a sample injector or a sample application unit.

According to one embodiment, the separation device can be designed as a chromatographic separation device, in particular as a chromatography separation column. In a chromatographic separation, the chromatographic separation column may be provided with an adsorption medium. At this, the fluidic sample can be stopped and only then with appropriate eluent (isocratic) or in the presence of a specific solvent composition (gradient) fractionally detached again, thus the separation of the sample is accomplished in their fractions.

 The sample separation device may be a microfluidic measuring device, a life science device, a liquid chromatography device, a high performance liquid chromatography (HPLC), an UHPLC device, an SFC (Supercritical Liquid Chromatography) device, a gas chromatography device, an electrochromatography device, and / or a gel electrophoresis device , However, many other applications are possible.

 For example, the fluid drive or fluid pump may be configured to convey the mobile phase through the system at a high pressure, for example, from a few hundred bars up to 1000 bars or more.

 The sample separation device may comprise a sample injector or a sample introduction unit for introducing the sample into the fluidic separation path. Such a sample injector may comprise a syringe-dockable injection needle in a corresponding fluid path, which needle may be withdrawn from that seat to receive sample, wherein upon reintroduction of the needle into the seat, the sample is in a fluid path which, for Example, by switching a valve, can be switched into the separation path of the system, which leads to the introduction of the sample in the fluidic separation path.

 The sample separator may include a fraction collector for collecting the separated components. Such a fraction collector may carry the various components, for example, into different liquid containers. The analyzed sample can also be fed to a drain tank.

 Preferably, the sample separation device may comprise a detector for detecting the separated components. Such a detector may generate a signal which can be observed and / or recorded and which is indicative of the presence and amount of sample components in the fluid flowing through the system.

BRIEF DESCRIPTION OF THE FIGURES

 Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more particular description of embodiments taken in conjunction with the accompanying drawings. Features that are substantially or functionally the same or similar are given the same reference numerals.

1 shows a trained as HPLC system sample separation device with a detection device according to an exemplary embodiment of the invention.

2 shows a part of a sample separation device with a detection device according to an exemplary embodiment of the invention.

3 and 4 show a valve assembly of a fluid valve and a detection device for electrically detecting a state of the fluid valve according to an exemplary embodiment of the invention, wherein the fluid valve in 3 closed and in 4 is open.

5 and 6 show a fluid valve and a detection device for optically detecting a state of the fluid valve according to an exemplary embodiment of the invention, wherein the fluid valve in FIG 5 closed and in 6 is open.

7 and 8th show a fluid valve and a detection device for fluorescence-based detection of a state of the fluid valve according to an exemplary embodiment of the invention, wherein the fluid valve in 7 closed and in 8th is open.

9 FIG. 12 is a graph showing, depending on the time, the course of a response that changes characteristically when a fluidic valve equipped with a detection device according to an exemplary embodiment of the invention is switched. FIG.

10 11 shows a diagram from which it can be seen how the reproducibility or correctness of a solvent composition in a sample separator can be increased on the basis of a dynamic detection of the state of a valve according to an exemplary embodiment of the invention.

11 shows a fluid valve with a detection device for electrically detecting a State of the fluid valve according to an exemplary embodiment of the invention.

12 shows a fluid valve with a detection device for optically detecting a state of the fluid valve according to an exemplary embodiment of the invention.

13 shows a fluid valve with a detection device for detecting a state of the fluid valve by means of a signal converter according to an exemplary embodiment of the invention.

 The illustration in the drawings is schematic.

Before describing exemplary embodiments with reference to the figures, some basic considerations will be summarized based on which exemplary embodiments of the invention have been derived.

According to an exemplary embodiment, a valve state in a sample separator is determined by detecting the transmissibility of a signal through a fluidic flow path of the valve in its respective state (i.e., whether it is fully or partially opened or closed).

 To control a sample separation device, it is advantageous to know the current state of a fluidic valve (in particular a gas valve or a liquid valve). It is not always possible or desirable to determine this information based on the presence of flow through the fluidic valve, or on the desired state, expected state, or estimate. It is also advantageous for certain control tasks to know the status information about a valve state dynamically (that is to say in particular with respect to its time profile), which is not always or simply not possible with the static detection of pressure or flow rate in the region of the valve. This problem relates in particular to fluidic valves of a sample separation device, in particular in HPLC (more particularly in UHPLC). In particular, the knowledge of such information is advantageous for the operation of valves, whose switching operation is particularly time-critical, in particular of Proportionierventilen (for example, a MultiChannel gradient valve) for proportioning individual solvent components to a mobile phase. But active or passive check valves of a sample separation, in particular a HPLC system, are exposed to the problem described.

 According to an exemplary embodiment, the transmission of a signal is measured through a flow path of the fluid modulated by the valve. It can be used with advantage the circumstance that the transmission capability of the signal through the fluid in the immediate vicinity of the valve structure often varies depending on its state (especially in the open state of the valve is higher than in the closed state).

 According to an exemplary embodiment, an electrical signal is used as the stimulus signal for detecting a state of a valve. In particular, if an electrically conductive fluid or a fluid having a comparatively high dielectric constant is used, it makes sense to detect the electrical properties of an associated portion of the fluidic path with the valve. Depending on the conductivity of the nearest part of a fluid line, it may be useful to place corresponding sensing electrodes near switching elements of the valve. Advantageously, these switching elements can be made according to the described embodiment of an electrically insulating material. The electrical conductivity can be determined by analyzing the response to the coupling of the stimulus signal. In this case, an alternating electrical signal is preferably used as the stimulation signal, in particular an alternating current signal with a high frequency in order to avoid artefacts due to electromigration and electrolysis. For example, according to such an embodiment, on one side of the valve, an electrical signal source can be arranged as a stimulus device and an electrical signal receiver can be attached to the other side of the valve as the detection device. When the valve is open, the electrical signal on the receiver side is significantly higher than in another state where the valve is closed.

 According to another embodiment, a light signal is used as the stimulation signal. For example, a light emitter may be arranged as a stimulator on one side of the valve, and a light sensor may be arranged as a detector on the other side of the valve. In an open state of the valve, when the flow path has an opening that can be penetrated by the fluid and light, the light sensor can detect the light. Conversely, if in a closed state of the valve, the flow path has no opening that can be penetrated by the fluid and light, the light sensor can not detect light. Advantageously, in such an embodiment, the valve components may be made from a non-transparent material at the wavelength used.

According to yet another exemplary embodiment, a signal converter may be used to detect the condition of a valve. In this case, for example, a sent back signal can be detected as an answer and provide information about the state of the valve. In such an embodiment, for example, a light emitter as a stimulating means and a light receiver as detecting means may be arranged on the same side of the valve. A signal converter, in particular designed as a fluorescent material, can be arranged on the other side of the valve. The permeability of the valve and thus the state can be detected by detecting a response signal of the signal converter. In the example of the fluorescent material, fluorescence radiation can be detected. If such a response signal is detected, it can be concluded that the valve is fully or partially open. If the valve is closed, the particular optical (alternatively electric) stimulation signal can not pass through the valve, so that no response signal can be detected. It should also be noted that in the detection of the state of a valve by means of a signal converter, other stimulation signals are possible than optical. For example, an electrical stimulus signal can excite a corresponding electroluminescent material by electroluminescence.

 It should also be noted in general that other types of signal can be used to detect the condition of a valve as an alternative to electrical and optical signals. For example, an acoustic signal, a heat signal, or a heat radiation signal may be coupled into the flow path of the valve, and an answer thereto may be detected on the other side of the valve.

1 shows an HPLC system as an example of a sample separator 10 with a control device coupled thereto 70 according to an exemplary embodiment of the invention.

1 shows the basic structure of an HPLC system as an example of a sample separation device 10 trained measuring device, as it can be used for example for liquid chromatography. A fluid pump as a fluid drive 20 containing solvents from a supply unit 25 supplied drives a mobile phase through a separator 30 (such as a chromatographic column) containing a stationary phase. A degasser 27 can degas the solvents before they drive the fluid 20 be supplied. A sample application unit 40 is between the fluid pump 20 and the separator 30 arranged to introduce a sample liquid in the fluidic separation path. The stationary phase of the separator 30 is suitably chosen and intended to separate components of the sample. A detector 50 a flow cell detects separated components of the sample, and a fractionator may be provided to dispense separated components of the sample into dedicated containers. Liquids no longer needed can drain into a drain 60 be issued.

A control device 70 controls the individual components 20 . 25 . 27 . 30 . 40 . 50 . 60 of the meter 10 ,

1 It can also be seen that at various points of the sample separator 10 fluidic valves 95 can be implemented. For example, one or more fluidic valves 95 on and / or in the fluid drive 20 be implemented as closer in 2 shown. Fluidic valves 95 in connection with the fluid drive 20 may be coupled in particular as non-return valves before or between individual stages of a multi-stage piston pump in the fluidic path. Fluidic valves 95 related to the operation of the fluid drive 20 For example, a proportioning valve may be used to proportion different solvents of a solvent composition as a mobile phase. As further in 1 also includes the sample application unit 40 one or more fluidic valves 95 , For example, such a fluidic valve 95 be designed as a rotor valve in which to form different fluid coupling fluid ports (for example, ports) of a stator with fluid lines (in particular grooves) of a rotor depending on a particular switching state of the rotor valve can be fluidly coupled or fluidly decoupled from each other. As fluidic valves 95 of the Probetrenngeräts 10 So can in particular a Proportionierventil, a check valve, in particular a passive, semi-active or active ball-seat valve (ie without external drive, with a drive, the valve 95 can only open or only close, or with a drive, the valve 95 both open and close), an injector valve, etc. can be used.

To the controller 70 a precise and correct control of the sample separation device 10 to allow the control device 70 be supplied over a period of time with appropriate dynamic information, at which times the individual fluidic valves 95 in which switching positions or switching states are located. In particular, the control device 70 as the basis for the control of the sample separation device 10 Use information when, for how long, at which operating phases or in which Operating conditions, and / or to what extent the individual valves 95 are open or closed. For this purpose, as in 1 shown schematically, the individual fluidic valves 95 with a respective detection device 100 whose structure and function will be described in more detail below. The respective detection device 100 provides for the respective fluidic valve 95 that for a respective opening or closing state of a respective fluidic valve 95 of the sample separator 10 indicative information. This can be the control device 70 for controlling the sample separation device 10 or to use (particularly precise) rules, in particular for generating or correcting a solvent composition. 2 illustrates the positions of fluidic valves 95 and associated detection devices 100 in the area of the fluid drive 20 in detail.

2 shows a part of the sample separator 10 with the control device 70 according to an exemplary embodiment of the invention in a more detailed representation.

The feeder 25 according to 2 four supply lines 304 to 307 each of which is associated with a respective one of four fluid component sources 300 to 303 for providing a respective fluidic component A to D is fluidly coupled. A according to the embodiment shown in a Proportionierventil as a fluidic valve 95 integrated mixing device 29 is between the supply lines 304 to 307 and an inlet 189 a primary piston pump 111 arranged. The in the embodiment shown also proportioning mixing device 29 is by means of the control device 70 for modulating the composition of the fluid from packets of the fluidic components A to D upstream of the primary piston pump 111 by sequentially coupling selected ones of the feed lines 304 to 307 with the primary piston pump 111 controllable. This means that the control device 70 the proportioning mixer 29 (in particular according to a multiplexer scheme) so as to sequentially sequence fluid packets of the components of group A, B, C and D (not all four components need to be used, for example a composition of two components A, B may be generated ) through a fluid line 109 by a here designed as a check valve inlet valve as another fluidic valve 95 and through the inlet 189 the primary piston pump 111 flow. It should be noted that other proportioning devices can be implemented as the proportioning valve according to 2 , It is also possible to use a mixing device 29 form together with a Proportioniereinrichtung, or separately. The mixing device 29 or the proportioning device has the fluidic valve 95 on, which may be formed, for example, as a rotor valve. The fluidic valve 95 the proportioning device has a plurality of flow paths (four here, one for each solvent component A, B, C or D), of which no more than one is opened at any time (the respective solvent component A, B, C being opened by the respective opened flow path or D can flow).

The primary piston pump 111 (see also reference numeral "I"), by means of the feeder 25 fluid to be pumped with a time-varying solvent composition (for example, according to a gradient run) can be fed, has one for conveying the fluid in a primary piston chamber 117 Reciprocatable arranged primary piston 115 on. The primary piston 115 and one between the primary piston pump 111 and a secondary piston pump 162 (see also reference numeral "II") switched and here also designed as a check valve further fluidic valve 95 (in a fluidic connection line 187 ) for selectively enabling or disabling fluid communication between the two piston pumps 111 . 162 are optionally also by means of the control device 70 controllable (this fluidic valve 95 For example, by means of the control device 70 must be controllable or designed as a passive valve, not in the middle of the connecting line 187 be arranged, but this can also be upstream or downstream). The secondary piston pump 162 is by means of the primary piston pump 111 pumped fluid can be supplied if that between the two piston pumps 111 . 162 arranged fluidic valve 95 is in a corresponding switching state (for example, when the pressure in the primary piston pump 111 is higher than in the secondary piston pump 162 , whereby the interposed fluidic valve 95 For example, by means of the control device 70 controllable or can be designed as a passive valve, can open). The secondary piston pump 162 has one for conveying the fluid in a secondary piston chamber 120 Reciprocatable arranged secondary piston 188 on, its position and / or speed also by means of the control device 70 is controllable and puts at its outlet 180 Fluid ready through a fluid line 121 and finally into the sample separator 30 and then into the detector 50 flows. Preferably, the piston pumps produce 111 and 162 in a coordinated function a continuous and substantially pulsation-free flow. Furthermore, the arrangement according to 2 have a different number of piston or syringe pumps, for example, one or four, which are not necessarily consecutively connected (ie as a primary and secondary) but also in parallel. Also is a use of Displacement pumps of other types, such as diaphragm pumps, possible.

The control device 70 is also programmatically set up so that it changes the composition of the fluidic solvent in time according to a predetermined time-varying composition profile. The predetermined temporal composition profile may in particular be a gradient profile for a chromatographic separation of the fluidic sample. Parameters for such a gradient profile or for a chromatographic method can be stored in a memory device or database 172 stored on which the control device 70 can access. With reference number 199 is shown schematically such a gradient profile in which the percentage% B of the fluidic component B (for the example of a mixture with one or more of the fluidic components A, C and D, respectively) varies as a function of the time t.

As in 2 shown is each of the fluidic valves 95 (Alternatively, only one or only a part of the fluidic valves 95 ) a respective detection device 100 associated with the current state (in particular open or closed) of the respective valve 95 can detect (as with reference to 3 to 8th . 11 to 13 will be described in detail). This information can be from the respective detection device 100 the control device 70 provided with this information for controlling the sample separation device 10 can use. valves 95 with multiple flow paths 104 (for example, the valve 95 the proportioning device) can with multiple detection devices 100 be equipped, for example, a respective detection device 100 per flow path.

Advantageously, the detection device 100 for dynamically determining the for the opening or closing state of the individual valves 95 be set up indicative information over the course of time. The detection device 100 or the controller 70 In particular, it can be set up, based on the dynamically determined time course, a functional accuracy of a pump when creating a solvent composition of the fluid in the sample separation device 10 to monitor. The proportioning mixer 29 is a valve 95 associated packages of the individual solvent components A, B, C and D respectively adds to the flowing fluid. The knowledge of the valve position of the associated valve 95 Over time and, for example, its comparison with a desired value thus makes it possible to determine the accuracy and accuracy of the contributions of the solvent components A, B, C and D in the total fluid flow. The detection of the state of the valve 95 the proportioning mixer 29 can by the associated detection device 100 be performed and the controller 70 be communicated. Any discrepancies between an actual value and a desired value of the solvent composition can be determined by the control device 70 be compensated by, for example, the valve 95 the proportioning mixer 29 is controlled corrective. In a corresponding manner, for example, a flow rate of the fluid in the sample separator 10 , a pressure value in the sample separator 10 and / or control information for controlling the fluid drive 20 of the sample separator 10 from the means of the detection device 100 Detected information to be determined or derived, in particular with regard to their deviations from predetermined or expected values. As a result, thus, the accuracy of the solvent composition in the sample separator 10 increases and therefore the reproducibility and reliability of an analysis result can be improved.

3 to 8th and 11 to 13 show exemplary embodiments of detection devices 100 , which are for the individual fluidic valves 95 according to 1 respectively. 2 can be implemented. It should be noted that the embodiments according to 3 to 8th such as 11 to 13 each for a check valve as an example of a fluidic valve of a sample separator 10 are shown. However, it will be apparent to one skilled in the art that other types of fluidic valves 95 can be configured accordingly. For example, a rotor valve (for example, the sample application unit 40 according to 1 or the proportioning / mixing device 29 according to 2 ) with one or more detection devices 100 corresponding 3 to 8th respectively. 11 to 13 be equipped. In such a rotor valve or other multi-way valve in which there are several fluidic flow paths (see reference numeral 104 ) and in which in a respective switching state of the valve, a flow of any, one, several or all paths or flow paths is allowed, for example, for each flow path, a separate detection device 100 are provided, which sensor the switching state of the valve 95 capture by the detection devices 100 for each individual flow path detect whether the respective flow path at a certain time or within a certain time interval is open or closed.

3 and 4 show a fluidic valve 95 and a detection device 100 for electrically detecting a condition of the fluidic valve 95 according to an exemplary embodiment of the invention, wherein the fluidic Valve 95 in 3 closed and in 4 is open.

The valve 95 according to 3 and 4 is designed as a passive check valve and has a valve seat 190 , A here designed as a ball movable valve body 192 and a biasing device formed here as a mechanical spring 194 for mechanically biasing the valve body 192 in the valve seat 190 on. The pretensioner 194 ensures that at low pressure differences between a fluid line 196 upstream of the valve 95 (see the arrows in 4 indicating the flow direction of the fluid) and another fluid line 198 downstream of the valve 95 the passive valve 95 in the 3 shown closed state is located. Only when the differential fluid pressure between a position immediately upstream of the valve 95 and another position immediately downstream of the valve 95 exceeds a threshold, the valve body 192 under the pressure of the flowing fluid according to 4 pressed to the right, so the valve 95 then the in 4 illustrated opening state occupies.

In the area of the valve 95 is a detection device 100 for detecting a condition of the valve 95 of the sample separator 10 indicative information. More specifically, in the check valve according to 3 and 4 to be detected state information of the valve 95 the information, whether the valve 95 straight (like in 3 shown) closed or (as in 4 shown) is opened.

To detect this, the detection device 100 a stimulus device 102 for emitting a stimulus signal into a fluidic flow path 104 of the valve 95 on. Advantageously, the stimulus device 102 to emit a high-frequency (for example, with a frequency of at least 10 kHz) electrical alternating signal as a stimulation signal, in particular to avoid unwanted electrolysis of an electrically conductive fluid. More specifically, the stimulus device is 102 according to 3 and 4 configured to provide an alternating electrical current as an electrical stimulation signal in the fluidic flow path 104 of the valve 95 to be transported by an electrically conductive fluid. The stimulus device 102 has a stimulation electrode for this purpose 110 for introducing the stimulus signal upstream of the fluidic valve 95 on. An acquisition device 106 has a detection electrode 112 for detecting the response to the stimulus signal downstream of the fluidic valve 95 on. The stimulation electrode 110 and the detection electrode 112 For example, at a respective inner surface of the respective fluid conduit 196 . 198 or directly on the valve body (for example on the valve seat 190 ) are applied (in particular vapor-deposited).

The detection device 106 the detection device 100 is used to detect a response resulting from the stimulus signal indicative of an ability of (from the valve 95 controlled) fluid, in the current state of the fluidic valve 95 through the fluidic valve 95 of the sample separator 10 to be able to flow (see 4 ) or not to be able to flow (see 3 ). According to 3 and 4 is the capture device 106 set up a response of the system according to 3 and 4 due to transport of electric current through the electrically conductive fluid at the detection electrode 112 capture. However, the capture device is 106 positioned the answer in the form of the fluidic flow path 104 only to detect, detect or detect the passing electrical stimulation signal when the fluidic valve 95 is in an open state and the electrical stimulation signal by means of the electrically conductive fluid through the fluidic flow path 104 of the valve 95 can be passed through (see 4 ). In the closed state of the valve 95 according to 3 on the other hand, such an electrical stimulation signal can not affect the now interrupted fluidic flow path 104 and therefore can not pass through the detection device 106 downstream of the valve 95 be recorded. It is advantageous if the constituents of the valve 95 (In particular, the valve seat 190 , the valve body 192 , the pretensioner 194 as well as the fluid lines 196 . 198 ) are made of an electrically insulating material or at least in the immediate vicinity of the valve 95 and / or in particular of the electrodes at the points have an electrically insulating surface coating, where it can come into contact with the fluid. In other words, all are preferably the flow path 104 at its separation point (ie at the point where the flow path 104 is interrupted or opened, depending on the switching state of the valve 95 ) limiting components of the fluidic valve 95 according to 3 and 4 made of an electrically insulating material. Therefore, one of the detection means 106 electrical signal detected in response to the emission of the electrical stimulus signal provides information about the valve condition. According to 3 and 4 are the stimuli device 102 , the recording device 106 and the flow path 104 of the fluidic valve 95 arranged relative to each other such that the stimulation signal only in the opened state of the fluidic valve 95 according to 4 and not in the valve closed state according to 3 from the stimulation electrode 110 the stimulus device 102 through the flow path 104 up to the detection electrode 112 of the Erfasseinrichtung 106 can propagate and can be detected there as an answer.

Furthermore, the detection device 100 a detection device 108 for determining the state indicative information based on the response to. The determination device 108 can with the stimulus device 102 and with the detection device 106 be coupled, for example, synchronize their operation. More precisely, the detection means 108 set up, based on the answer as for the state indicative information to determine whether the fluidic valve 95 is open or closed. Furthermore, the determination device 108 set up a transition of the fluidic valve 95 from a closed state to an open state based on a sudden increase in a strength of the response or a transition of the fluidic valve 95 to recognize from an open state to a closed state by means of a sudden decrease in a strength of the response (cf. 9 ).

The detection of the valve state is carried out according to 3 and 4 as follows: By means of the stimulation electrode 110 the electrical stimulation signal is transmitted as an electrical current into the electrically conductive fluid passing through the valve 95 is fed, fed. Only if the valve 95 according to 4 is open, the electrical stimulation signal can up to the detection electrode 112 propagate and recorded there as an electrical signal. When the valve 95 according to 3 is closed, given the electrically insulating design of the corresponding valve components, there is no coherent electrical path from the stimulation electrode 110 to the detection electrode 112 at which the electrical stimulation signal therefore does not arrive. The determination device 108 can be the opening or closing state of the valve 95 according to 3 and 4 So determine and this information the controller 70 as a basis for controlling the sample separation device 10 to transfer.

Stands in the fluid lines 196 . 198 no electrically conductive fluid available, but dielectric fluid is promoted, the reference to 3 and 4 As described, the power line based detection of the valve state can be replaced by a capacitive detection of the valve state, which clearly shows the electrodes 110 . 112 how capacitor plates and the dielectric fluid act as a dielectric of the capacitor. Expressed in clear terms, the capacity of the arrangement then changes between the closed valve state according to FIG 3 and the open valve state according to 4 so that a capacitive measurement allows conclusion to the valve state. In other words, in this case, detection of an active current (via the active resistance of the measurement path) can be replaced by detection of a reactive current (via the reactive resistance of the measurement path).

5 and 6 show a fluidic valve 95 and a detection device 100 for optically detecting a condition of the fluidic valve 95 according to an exemplary embodiment of the invention, wherein the fluidic valve 95 in 5 closed and in 6 is open.

In contrast to 3 and 4 is according to 5 and 6 the stimulus device 102 configured, an optical stimulus signal (for example, a light pulse, a continuous light signal or a sequence of light pulses) in the fluidic flow path 104 of the valve 95 for propagating along a visually transparent to the visible light fluid. In a corresponding manner is according to 5 and 6 the detection device 106 arranged, an optical response (that is, up to the detection device 106 propagating light of the stimulus device 102 ) only if the fluidic valve 95 is in an open state (see 6 ). For this purpose, the stimulus device 102 a light source as an electromagnetic radiation source 114 for emitting the optical stimulation signal upstream (or downstream) of the fluidic valve 95 and can the capture device 106 a light detector as electromagnetic radiation detector 116 for detecting the response downstream (or upstream of the fluidic valve 95 exhibit. In order to ensure a distinction between detection light and scattered light, the stimulation device can advantageously be used 102 emit a frequency-modulated optical light signal as a stimulus signal. The electromagnetic radiation source 114 can then be formed, for example, as a laser diode, the detection device 116 as a photodiode. In order in the closed valve state according to 5 at the detection device 106 to measure no unwanted detection signal, according to 5 and 6 beneficial all the flow path 104 limiting components of the fluidic valve 95 be made of an optically impermeable material. 5 and 6 further show a first optical fiber 191 (For example, a first optical fiber) for coupling the optical stimulation signal from the electromagnetic radiation source 114 in the fluid-carrying lumen of the fluid line 196 , In a similar way is in 5 and 6 in addition, a second light guide 193 (For example, another optical fiber) for coupling the in the fluid line 198 propagated optical stimulation signal from the fluid-carrying lumen of the fluid line 198 in the electromagnetic radiation detector 116 arranged.

The detection of the valve state is carried out according to 5 and 6 in the following way: By means of the electromagnetic radiation source 114 is controlled by the stimulus device 102 , the optical stimulus signal as visible light into the optically transparent fluid passing through the valve 95 is fed, fed. Only if the valve 95 according to 6 is open, the optical stimulation signal can up to the second light guide 193 and from there to the electromagnetic radiation detector 116 propagate and recorded there as an optical signal. When the valve 95 according to 5 is closed, there is no continuous optical path from the first light guide in view of the opaque design of the corresponding valve components 191 to the second light guide 193 at which the optical stimulus signal therefore does not arrive. The determination device 108 can be the opening or closing state of the valve 95 according to 5 and 6 So determine and this information the controller 70 as a basis for controlling the sample separation device 10 to transfer. It should be noted that no route with direct view of the light guide 191 on the light guide 193 necessary is. Advantageously, this can also be done once or several times on the elements of the valve 95 reflected or scattered light can be detected as a response signal.

7 and 8th show a fluidic valve 95 and a detection device 100 for fluorescence-based detection of a state of the fluidic valve 95 according to an exemplary embodiment of the invention, wherein the fluidic valve 95 in 7 closed and in 8th is open.

As per 5 and 6 is also according to 7 and 8th the opening or closing state of the valve 92 detected by an optical detection. However, according to 7 and 8th different than according to 5 and 6 the stimulus device 102 and the detection device 106 on the same valve side, ie in this example both upstream of the valve 95 , Downstream of the valve 95 is, however, according to 7 and 8th a signal converter 118 (For example, formed as a wall coating of the fluid line 198 ) intended.

According to 7 and 8th has the stimulus device 102 again an electromagnetic radiation source 114 for emitting the electromagnetic stimulation signal, which by means of optical fibers 191 into the lumen of the fluid line 196 upstream of the valve 95 is coupled. The detection device 106 has an electromagnetic radiation detector 116 for detecting a response signal in response to the transmission of the stimulus signal. The signal converter 118 is arranged to generate upon application of the electromagnetic stimulation signal, the electromagnetic response signal having a different, in particular lower frequency or greater wavelength compared to the electromagnetic stimulation signal. According to 7 and 8th is the signal converter 118 formed as a fluorescent material which is adapted to generate upon irradiation with the electromagnetic stimulation signal of a stimulation frequency by means of fluorescence electromagnetic radiation of a modified frequency as a response signal. In the illustrated embodiment, the signal converter 118 as a coating of an inner wall of the fluid line 198 formed, for example, made of ruby. Given the fluorescent properties of ruby is the signal converter 118 configured to generate a responsive signal distinguishable from the electromagnetic stimulus signal due to the frequency shift. The electromagnetic radiation detector 116 the detection device 106 is to achieve a frequency selectivity with a wavelength or frequency filter 181 at the detection device 106 Mistake. The frequency filter 181 may be configured so that only the electromagnetic response signal has a suitable frequency, the frequency filter 181 to happen and by means of the detection device 106 but not the electromagnetic stimulus signal with its other frequency.

The detection of the valve state is carried out according to 7 and 8th in the following way: By means of the electromagnetic radiation source 114 is controlled by the stimulus device 102 , the electromagnetic stimulation signal (for example, blue light) in the fluid passing through the valve 95 be fed, fed. Only if the valve 95 according to 8th is open, the electromagnetic stimulation signal can be the signal converter 118 reach from ruby directly or as reflected or scattered light and there trigger the generation of the electromagnetic response signal in the form of frequency-shifted electromagnetic secondary radiation (recognizable as red glow of the ruby). The response signal can only in the open state of the valve 95 according to 8th be generated and to the electromagnetic radiation detector 116 propagate, the frequency filter 181 happen and then by means of the detection device 106 be recorded. When the valve 95 according to 7 is closed, there is no passable optical path from the optical fiber in view of the opaque design of the corresponding valve components 191 to the signal converter 118 at which the electromagnetic stimulation signal therefore does not arrive at all. The determination device 108 can be the opening or closing state of the valve 95 according to 7 and 8th So determine and this information the controller 70 as a basis for controlling the sample separation device 10 to transfer.

9 shows a diagram 200 which, depending on the time, represents the course of a response that changes characteristically when an associated fluidic valve 95 is switched. The diagram 200 has an abscissa 202 along which time is plotted. Along an ordinate 204 is one of the capture device 106 according to 3 respectively. 4 plotted detectable electrical signal that can be measured when using the stimulus device 102 an electric current having a frequency of, for example, 10,000 Hz is fed into the fluid. Will the valve 95 from an opening state (area on the left of reference numeral 206 ) to a closed state (area right hand of reference numerals 206 ), as indicated by reference numerals 206 Fig. 10 illustrates a sudden signal drop indicating detection of the switching of the valve 95 and the dynamic detection of its switching state as a function of time allowed.

The experiment according to 9 was carried out with 0.2% formic acid in water as a fluid on a model valve. It can be seen in the range of reference numerals 206 over about two to three periods of the carrier frequency, an additional short opening phase of the valve 95 , Even higher carrier frequencies lead to an even more precise detection of such transient states and thus to a further refinement of the temporal resolution of a valve switching time. In addition, high carrier frequencies of 10 kHz and more can advantageously prevent unwanted effects in the conductive fluid, particularly electrolysis.

10 shows a diagram 400 which can be seen as based on a dynamic detection of the state of a valve 95 and thus a precise determination of opening times or periods according to an exemplary embodiment of the invention, the reproducibility or correctness of a solvent composition in a sample separation device 10 can be increased.

The diagram 400 has an abscissa 402 along which time is plotted. Along an ordinate 404 is a piston position of a piston pump (see reference numeral 111 respectively. 162 in 2 ) applied.

Below the diagram 400 associated operating states of the piston pump are applied. A distinction is made between a respective delivery phase 406 . 408 and a suction phase 410 that occur between two consecutive delivery phases 406 . 408 lies. An associated inlet valve associated with the piston pump (see reference numeral 95 directly upstream of the piston pump 111 or directly upstream of the piston pump 162 in 2 ) can during the delivery phases 406 . 408 closed and during the intake phase 410 to be open. One with reference number 412 illustrated time interval corresponds to a process of decompressing a residual volume in the pump 111 , Only when a channel or flow path 104 of the respective valve 95 opened, solvent packages of appropriate solvents (in 10 with A, B, C, A called) are sucked. The flow of solvent in the intake path is with a curve 414 shown.

A box 416 symbolizes a temporal uncertainty concerning the exact moment of the beginning of the intake phase 410 , which corresponds to a valve switching. The suction phase can not begin until the decompression phase has ended; however, the duration of the decompression phase is not necessarily well known a priori, for instance due to uncertainty or inaccuracy of the assumptions on the compressibility of the fluids, the elasticity of the system behavior, etc. Thus, the exact beginning of the aspiration phase 410 linked with an indeterminacy or temporal blur ..

10 schematically shows a stroke cycle of a quaternary pump, for example implemented as a fluid drive 20 a sample separator 10 , The inflow of solvent begins upon completion of the decompression phase, indicated by reference numerals 412 , Information characterizing this event is not directly available, especially not in real time. Only one estimation can be made, the exact timing being subject to uncertainty with a bias component and a jitter. However, knowledge of the exact timing of the initiation of solvent saponification is important to predict and control the volume of total solvent soak, particularly the volume of the first solvent package (in 10 on the left side with A).

When according to an exemplary embodiment of the invention, dynamically monitoring the state of an associated valve 95 by means of a detector device 100 takes place, the opening or closing state of the respective valve 95 can be precisely determined and used as a direct indicator of the beginning of the solvent suction. The generation of the solvent composition can thereby be more correct and precise, which consequently also the correctness and reproducibility of results of a sample analysis by means of a Probetrenngeräts 10 improved. Illustratively, a detection device 100 the width of the blur interval 416 reduce, as a switching time of the associated valve 95 can be determined more precisely.

11 shows a fluidic valve 95 with a detection device 100 for electrically detecting a condition of the fluidic valve 95 according to an exemplary embodiment of the invention. The embodiment according to 11 resembles that according to 3 and 4 , According to 11 is the detection device 100 in the valve 95 integrated. In 11 are electrical signal lines 210 . 212 shown the stimulus device 102 or the detection device 106 assigned. Further, on the signal line 212 a pre-processing device 214 for pre-processing one along the signal line 212 connected signal. This preprocessing may include, for example, signal amplification and / or signal analysis. Optionally, the preprocessing device 214 with the stimulus device 102 which also functions as an AC signal source. The determination device 108 can according to 11 also take on tax tasks. For example, the determiner 108 determine the valve state and in particular the dynamic change of a valve state over time and (possibly cooperating with control device 70 ) the operation of the sample separator 10 and / or the subsequent switching of the valve 95 based on the detected (static or dynamic) valve state information.

12 shows a fluidic valve 95 with a detection device 100 for optically detecting a condition of the fluidic valve 95 according to an exemplary embodiment of the invention. The embodiment according to 12 resembles that according to 5 and 6 , According to 12 is the detection device 100 in the valve 95 integrated. In 12 are optical signal lines 220 . 222 shown the stimulus device 102 or the detection device 106 assigned. Further, to the signal line 222 a pre-processing device 224 for pre-processing one along the signal line 222 connected signal. This preprocessing may, for example, comprise signal amplification and / or signal analysis or signal conversion. Optionally, the preprocessing device 224 with the stimulus device 102 be coupled. In 12 denotes reference numeral 240 the optical stimulus signal.

13 shows a fluidic valve 95 with a detection device 100 for detecting a condition of the fluidic valve 95 by means of a fluorescence-based signal converter 118 according to an exemplary embodiment of the invention. The embodiment according to 13 resembles that according to 7 and 8th , According to 13 is the detection device 100 in the valve 95 integrated. The embodiment according to 13 has some of the components referring to 12 have been described.

For example, the electromagnetic radiation source 114 generate blue light as an optical stimulus signal and by means of the optical signal line 220 in the valve 95 inject. Only if the valve 95 is in the open state (as in 13 shown as the valve body 192 from the valve seat 190 led out), the optical stimulation signal to the here in the region of the valve seat 190 arranged (for example, annular) signal converter 118 (For example, a fluorescent Rubinkörper) get there and generate electromagnetic fluorescence radiation in the form of red light as a response signal. This can be done through the optical signal line 222 to the capture device 106 reach. The preprocessing device 224 can according to 13 a signal discriminator (in particular designed as a frequency filter 181 ), which can pass the red light to be detected and filter away the blue light that is not relevant for the detection. In 13 denotes reference numeral 240 the electromagnetic stimulus signal and reference numerals 250 the electromagnetic response signal caused by fluorescence on the annular signal transducer 118 is generated when this with the electromagnetic stimulation signal 240 is irradiated. It should be noted that the input and output of the stimulus and response signal in this example can also be done via the same light guide, the separation of the stimulation and response signal paths only in the detection device 100 (using light filters or dichroids, etc.).

It should be noted that the term "comprising" does not exclude other elements and that the "on" does not exclude a plurality. Also, elements described in connection with different embodiments may be combined. It should also be noted that reference signs in the claims should not be construed as limiting the scope of the claims.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 0309596 B1 [0002]

Claims (20)

Detection device ( 100 ) for detecting a condition of a fluidic valve ( 95 ) of a sample separation device ( 10 ) indicative information, wherein the detection device ( 100 ) comprises: a stimulus device ( 102 ) for sending a stimulus signal into a fluidic flow path ( 104 ) of the valve ( 95 ); an acquisition device ( 106 ) for detecting or detecting a response resulting from the stimulus signal which is indicative of a capability of fluid in the present state of the fluidic valve ( 95 ) through the fluidic flow path ( 104 ) of the valve ( 95 ) to flow; and a determination device ( 108 ) for determining the state indicative information based on the response. Detection device ( 100 ) according to claim 1, wherein the determining device ( 108 ) is arranged to determine the information indicative of the condition over time. Detection device ( 100 ) according to claim 2, wherein the determining device ( 108 ) is arranged, based on the determined time course, to derive at least one information selected from a group, consisting of: one as a result of the function of the fluidic valve ( 95 ) expected solvent composition, in particular the accuracy of a solvent composition, the fluid in the sample separation device ( 10 ); one as a result of the function of the fluidic valve ( 95 ) expected flow rate of the fluid in the sample separation device ( 10 ); Pressure ratios, in particular a ratio of two pressure values, in the sample separation device ( 10 ); Control information for controlling the sample separation device ( 10 ), in particular a fluid drive ( 20 ) of the sample separation device ( 10 ). Detection device ( 100 ) according to one of claims 1 to 3, wherein the stimulation device ( 102 ) is adapted, an electrical stimulation signal in the fluidic flow path ( 104 ) of the valve ( 95 ) for propagation through the fluid. Detection device ( 100 ) according to claim 4, wherein the detection device ( 106 ) is adapted to detect at least one of a group consisting of: a response to the electrical stimulation signal due to a transport of electric current through the fluidic flow path ( 104 ) by means of an electrically conductive fluid; in response to a changing or alternating electrical stimulation signal due to a capacitive or reactive electrical current in the fluidic pathway ( 104 by a dielectric fluid; a response to the electrical stimulus signal due to capacitive behavior of a dielectric fluid due to application of an electrical voltage. Detection device ( 100 ) according to one of claims 1 to 5, wherein the stimulation device ( 102 ) a stimulation electrode ( 110 ) for transmitting the stimulation signal upstream or downstream of the fluidic valve ( 95 ), in particular a valve seat ( 190 ) of the valve ( 95 ), and the recording device ( 106 ) a detection electrode ( 112 ) for detecting the response to the stimulation signal downstream or upstream of the fluidic valve (FIG. 95 ), in particular a valve seat ( 190 ) of the valve ( 95 ), having. Detection device ( 100 ) according to one of claims 1 to 6, wherein the stimulation device ( 102 ) is arranged to emit an electrical alternating signal as a stimulation signal, in particular with a frequency of at least 10 Hz, more particularly with a frequency of at least 1000 Hz, preferably with a frequency of at least 10,000 Hz. Detection device ( 100 ) according to one of claims 1 to 7, wherein the stimulation device ( 102 ) is set up, an electromagnetic, in particular optical, stimulation signal in the fluidic flow path ( 104 ) of the valve ( 95 ) for propagating along a transparent, in particular optically transparent, fluid for the electromagnetic stimulation signal. Detection device ( 100 ) according to claim 8, wherein the detection device ( 106 ) is adapted to detect or detect an electromagnetic, in particular optical, response to the electromagnetic, in particular optical, stimulation signal only when the fluidic valve ( 95 ) is in an at least partially open state and the electromagnetic, in particular optical, stimulation signal by means of the transparent for the electromagnetic stimulation signal, in particular optically transparent, fluid through the fluidic flow path ( 104 ) of the valve ( 95 ) can be passed through Detection device ( 100 ) according to one of claims 1 to 9, comprising one of the following features: wherein the stimulation device ( 102 ) an electromagnetic radiation source ( 114 ) for transmitting the stimulation signal upstream or downstream of the fluidic valve ( 95 ), in particular a valve seat ( 190 ) of the valve ( 95 ), and the recording device ( 106 ) an electromagnetic Radiation detector ( 116 ) for detecting the response downstream or upstream of the fluidic valve ( 95 ), in particular a valve seat ( 190 ) of the valve ( 95 ), having; the stimulus device ( 102 ) an electromagnetic radiation source ( 114 ) for transmitting the stimulation signal and the detection device ( 106 ) an electromagnetic radiation detector ( 116 ) for detecting the response, wherein the stimulus device ( 102 ) and the detection device ( 106 ) on the same side of the fluidic valve ( 95 ) or the fluidic flow path ( 104 ), in particular both upstream of the fluidic valve ( 95 ), in particular a valve seat ( 190 ) of the valve ( 95 ) are arranged. Detection device ( 100 ) according to one of claims 1 to 10, wherein the detection device ( 100 ) a signal converter ( 118 ) arranged to generate the response upon application of the stimulus signal by converting the stimulus signal to a response signal differentiable from the stimulus signal. Detection device ( 100 ) according to claim 11, wherein the signal converter ( 118 ) is selected from a group consisting of: electromagnetic luminescent material, in particular fluorescent material and / or phosphorescent material, which is set up to generate electromagnetic radiation of changed frequency in response to irradiation with electromagnetic radiation as a stimulation signal; An electroluminescent material configured to generate electromagnetic radiation in response to an electrical stimulation signal. Detection device ( 100 ) according to claim 11 or 12, comprising at least one of the following features: wherein the signal converter ( 118 ) on one side of the fluidic valve ( 95 ) disposed on another side of the fluidic valve ( 95 ), on which other side the stimulus device ( 102 ) and the detection device ( 106 ) are arranged; the signal converter ( 118 ) is arranged to generate a response signal which can be distinguished from the stimulation signal, in particular distinguishable by means of a frequency filter ( 181 ) of or before the detection device ( 106 ). Detection device ( 100 ) according to one of claims 1 to 13, comprising at least one of the following features: wherein the stimulation device ( 102 ) for transmitting the stimulation signal and the detection device ( 106 ) for detecting the response are arranged such that the stimulus signal and the response are selected from a group consisting of an acoustic signal and a heat signal, in particular a heat radiation signal or a heat conduction signal; the stimulus device ( 102 ), the recording device ( 106 ) and the flow path ( 104 ) of the fluidic valve ( 95 ) are arranged relative to each other such that the stimulation signal only in an at least partially open state of the fluidic valve ( 95 ) from the stimulus device ( 102 ) through the flow path ( 104 ) to the capture device ( 106 ) and can be detected there as an answer; the determination device ( 108 ) is arranged to determine, based on the response as information indicative of the state, whether the fluidic valve ( 95 ), in particular the or a respective flow path ( 104 ) of the fluidic valve ( 95 ), opened or closed; the determination device ( 108 ) is arranged to determine, based on the response as information indicative of the state, to what degree the fluidic valve ( 95 ), in particular the or a respective flow path ( 104 ) of the fluidic valve ( 95 ), is open; the determination device ( 108 ) is arranged, a transition of the fluidic valve ( 95 ) from a closed state to an open state on the basis of an, in particular sudden, increase or, in particular abrupt, reduction of the response and / or a transition of the fluidic valve ( 95 ) from an open state to a closed state on the basis of a, in particular sudden, reduction or a, in particular abrupt, rise in the response to recognize. Valve arrangement for a sample separation device ( 10 ), comprising: a fluidic valve ( 95 ) with a fluidic flow path ( 104 ); a detection device ( 100 ) according to one of claims 1 to 14 for detecting a condition of the fluidic valve ( 95 ) indicative information. Valve arrangement according to claim 15, comprising a control device ( 70 ), which is set up based on the state of the fluidic valve ( 95 ) indicative information an operation of the sample separation device ( 10 ), in particular a piston movement of a fluid drive ( 20 ) of the sample separation device ( 10 ), in particular with respect to an amplitude and / or with respect to a speed of the timing of subsequent switching operations of the fluidic valve ( 95 ) or another fluidic valve ( 95 ) of the sample separation device ( 10 ); wherein the fluidic valve ( 95 ) at least one further fluidic flow path ( 104 ) having; comprising at least one further detection device ( 100 ) according to any one of claims 1 to 14; each of the detection devices ( 100 ) a respective one of the flow paths ( 104 ) and is adapted to detect whether fluid in the current state of the fluidic valve ( 95 ) is enabled by the respective associated fluidic flow path ( 104 ) of the valve ( 95 ) to flow. Sample Separator ( 10 ) for separating a fluidic sample, wherein the sample separation device ( 10 ) comprises: a fluid drive ( 20 ) configured to drive a mobile phase and the fluidic sample received therein; a sample separator ( 30 ) for separating the fluidic sample in the mobile phase; a fluidic valve ( 95 ) with one, depending on a state of the fluidic valve ( 95 ), at least partially open or closed flow path ( 104 ), which is to be flowed through by the mobile phase and / or the fluidic sample as fluid, when the valve ( 95 ) is at least partially open; and a detection device ( 100 ) according to one of claims 1 to 14 for detecting the condition of the fluidic valve ( 95 ) indicative information. Sample Separator ( 10 ) according to claim 17, further comprising at least one of the following features: wherein all the flow path ( 104 ) at its separation point limiting components of the fluidic valve ( 95 ) comprise or consist of an electrically insulating and / or an optically impermeable material; wherein the fluidic valve ( 95 ) is formed as at least one of a group consisting of a proportioning valve, a check valve, an injector valve, a rotor valve, a one-way valve and a multi-way valve; the sample separator ( 30 ) is designed as a chromatographic separation device, in particular as a chromatography separation column; the sample separator ( 10 ) is configured to analyze at least one physical, chemical and / or biological parameter of at least one fraction of the fluidic sample; the sample separator ( 10 ) comprises at least one of the group consisting of a chemical, biological and / or pharmaceutical analysis apparatus and a chromatographic apparatus, in particular a liquid chromatography apparatus, a gas chromatography apparatus, a supercritical liquid chromatography apparatus, an HPLC apparatus and a UHPLC apparatus; the fluid drive ( 20 ) is configured to drive the mobile phase at a high pressure; the fluid drive ( 20 ) is configured to drive the mobile phase at a pressure of at least 100 bar, in particular at least 500 bar, more particularly at least 1000 bar; the sample separator ( 10 ) is configured as a microfluidic device; the sample separator ( 10 ) is configured as a nanofluidic device; the sample separator ( 10 ) has a sample application unit ( 40 ) for introducing the fluidic sample into a fluidic path between the fluid drive ( 20 ) and the sample separation device ( 30 ) on; the sample separator ( 10 ) has a detector ( 50 ), in particular a fluorescence detector or UV absorption detector, for detecting the separated fluidic sample; the sample separator ( 10 ) has a sample fractionator ( 60 ) for fractionating the separated fluidic sample. Method for detecting a state of a fluidic valve ( 95 ) of a sample separation device ( 10 indicative information, the method comprising: emitting a stimulus signal into a fluidic flow path ( 104 ) of the valve ( 95 ); Detecting a response resulting from the stimulus signal that is indicative of a fluid's ability in the current state of the fluidic valve ( 95 ) through the fluidic flow path ( 104 ) of the valve ( 95 ) to flow; and determining the state indicative information based on the response. Use of by means of a detection device ( 100 ) according to one of claims 1 to 14, for a state of a fluidic valve ( 95 ) of a sample separation device ( 10 ) indicative information for controlling the sample separation device ( 10 ).

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