DE102019125170B4 - Detection system for charged aerosols, corresponding method and use - Google Patents

Abstract

Charged Aerosol Detector System (2000), the system comprising: a droplet generator (2003) designed to generate droplets, a drying unit (2005) designed to dry the droplets and thus generate particles, a charger configured to charge the particles, a current measuring unit (2010) configured to measure a current generated by the charged particles, and a measuring unit (100) configured to receive data for determining at least one parameter of the particles or the droplets, wherein the measuring unit (100) is upstream of the flow measuring unit (2010), wherein the at least one parameter is at least one size parameter for a size of the particles or the droplets; and / or at least one frequency parameter for a frequency of the particles or the droplets includes.

Description

The present invention relates generally to the field of charged aerosol detection (CAD). The invention is applicable to the field of chromatography, e.g. B. Liquid Chromatography (LC) and in particular the field of High Performance Liquid Chromatography (HPLC) and Ultra High Performance Liquid Chromatography (UHPLC).

LC is a technology based on chromatographic separation, in which a sample is separated into its components by pumping the sample through a chromatographic column together with an eluting solvent. Inside the column there is a solid that interacts with the liquid, i.e. the eluent containing the sample, with a strength of interaction that is characteristic of each component. Thus, different components can emerge from the column at different times depending on their respective strengths of interaction. In other words, the time it takes a component to leave the column is a characteristic of the component under the particular chromatographic conditions.

The components can thus be separated for later use or their proportions can be detected and quantified by a suitable detector downstream of the separation column. As the compound passes through the detector, a peak is obtained in the respective signal. Such a signal is called a chromatogram. Depending on the complexity of the sample, it consists of several peaks in quick succession.

HPLC systems can use different types of detection methods depending on the properties of the analyte or the system of interest. Some common detection methods include: Evaporative Light Scattering Detection (ELSD), which can be suitable for gradient and isocratic elution; Refractive Index (RI), with which an analyte can be detected based on the refractive index variation of the mobile phase; mass spectroscopic methods (MS) and methods based on spectroscopy of ultraviolet / visible light (UV-Vis). However, ELSD, MS and UV / Vis can be influenced by physical and / or chemical properties of the samples.

Another method is the detection of charged aerosols (CAD). CAD is a detection method capable of quantifying a particular chemical (or a variety of chemicals) in a sample after generating charged aerosol particles that are analyzed with an ammeter. CAD methods are widely used to quantify non-volatile and semi-volatile analytes and can provide a consistent analyte response regardless of chemical structure and molecular size.

In simple terms, CAD methods are independent of the presence of a chromophore, for example, and the ionization capacity of a molecule. Therefore, the detection of charged aerosols is able to provide an accurate and precise quantification of - without being limited to - lipids, carbohydrates, antibiotics, natural products, surfactants, biofuels, auxiliaries, amines and counterions that other detection methods, e.g. B. UV / Vis absorption, can not detect. In addition, detection methods of charged aerosols can provide a uniform response to measurements of analytes with chromophores and in particular independently of their extinction coefficient at a certain wavelength. CAD methods can also provide good quantitative estimates of unknown impurities, including degradation products. Thus, the detection methods for charged aerosols with respect to other detection methods, e.g. B. ELSD, considered beneficial in terms of sensitivity, dynamic range, and response uniformity.

For example disclosed US 6568245 B2 an aerosol detector, particularly for liquid chromatography applications, that includes a corona discharge source that is controlled to selectively charge the non-volatile residue particles of an aerosol. The aerosol initially consists of droplets of a liquid sample, the residue particles being created by droplet evaporation. The selectively charged residue particles are collected on a conductive filter. The electrical current along a conductor coupled to the filter is measured repeatedly or continuously to provide an indication of concentrations of the non-volatile material.

It also refers to US 2014/0352411 A1 on detectors of charged aerosols. In this document it is stated that it is desirable to produce a spray of droplets of uniformly small diameters. This document also relates to a nebulizer. The atomizer is equipped with a spray emitter for generating a droplet spray in a central area of a spray chamber. The central area is separated from an upper area by a horizontally protruding rib which defines a passage between the central and upper areas. The main direction of droplet movement within the upper region is essentially the reverse of the main direction of droplet movement within the central area. Larger droplets cannot curve from the center to the top and hit a back of the spray chamber.

While the prior art disclosures may be satisfactory in some respects, they nonetheless have certain disadvantages and shortcomings. In relation to US 2014/0352411 A1 the deposition of large droplets reduces the amount of analyte that reaches the detector, which can reduce measurement reliability. In addition, the method discussed can be highly dependent on the solvent used. That is, an amount of analyte in a first solvent can lead to a result that differs from a result with the same amount of analyte in a second solvent.

the US 5306412 A teaches the use of mechanical vibration to enhance the electrostatic dispersion of sample solutions into the small, highly charged droplets that ions from dissolved species can generate for mass spectrometric analysis. It is described that this is effective at ultrasonic frequencies for solutions with flow rates, conductivities and surface tensions that are too high for stable dispersion by electrostatic forces alone, such as with conventional electrospray ionization.

From the WO 02/075279 A1 an aerosol detector is known which is particularly suitable for liquid chromatography applications and which comprises a corona discharge source which is controlled in such a way that it selectively charges the non-volatile residue particles of an aerosol. The aerosol initially consists of droplets of a liquid sample, with the residue particles resulting from the evaporation of the droplets. The selectively charged residue particles are collected on a conductive filter. The electrical current along a conductor coupled to the filter is measured repeatedly or continuously to provide an indication of the concentrations of the non-volatile material.

the DE 102016007402 A1 discloses a system for the detection of non-volatile substances dissolved in a solution. The system comprises: a spray emitter system configured to receive a stream of solution and create an aerosol of droplets therefrom, the droplets produced having a limited range of sizes; a spray chamber adapted to receive the aerosol and to deliver a modified aerosol consisting of droplets with a diameter below a predetermined value; a conduit configured to receive a stream of the modified aerosol and evaporate the solvent to create an aerosol comprising particulate matter of the materials; a charging chamber configured to receive the aerosol and to apply an electrical charge to the particulate matter; and a detector configured to measure an amount of charge transferred to the solid particles, the limited size range being such that solid particles with diameters greater than 10 nm constitute a significant subset of all of the particles received by the charge chamber.

In view of the foregoing, it is an object to overcome, or at least mitigate, the deficiencies and disadvantages of the prior art. In particular, the present invention aims to provide a technology that enables the amount of analyte to be precisely determined. For example, the present invention can also aim to determine the amount of analyte independently of the solvent used.

These objects are achieved by the present invention.

A first aspect of the present invention relates to a Charged Aerosol Detector System (CAD system). The system comprises a droplet generator, which is configured to generate droplets, a drying unit, which is configured to dry the droplets and thus to generate particles, a charger, which is configured to charge the particles, and a current measuring unit, which is designed to measure a current generated by the charged particles. Furthermore, the system also comprises a measuring unit which is designed to provide data for determining at least one parameter of the particles or the droplets.

The system is thus able to determine the at least one parameter of the particles or the droplets. For example, a size parameter can be determined for a size of the droplet or particle, such as e.g. B. a size distribution.

The measuring unit can either be designed to observe the particles and provide data for determining the at least one parameter based on this observation, or to observe the droplets and provide data for determining the at least one parameter based on this observation.

This means that, depending on the position of the measuring unit within the system, it can be designed to observe either particles or droplets. Those skilled in the art will understand that droplets are the Droplet generator can occur downstream and upstream of the drying unit, while particles can typically occur downstream of the drying unit. In other words, droplets can typically comprise the effluent that is supplied to the droplet generator, while particles typically only comprise the analyte, since other parts of the effluent can be vaporized in the drying unit. It goes without saying that, depending on the exact position within the drying unit, both droplets and particles can be present within the drying unit.

The at least one parameter can comprise at least one size parameter for a size of the particles or droplets.

This can be advantageous for the following reason: It was found that the solvent dependency is mainly due to the fact that different solvents normally lead to different droplet size distributions. For example, the average droplet size differs depending on whether water or acetonitrile is used as the solvent.

However, the charging of the particles usually takes place in a diffusion charging process. During this process, the amount of charge deposited on a particle is roughly proportional to its diameter and thus to the third root of its volume (and the amount of sample). The creation of many small droplets thus leads to more charge being deposited and a higher current being measured. Since the droplet sizes (and thus also the particle sizes) depend on the solvent used, the resulting flow (for a given amount or concentration of analyte) depends on the solvent.

However, embodiments of the present invention determine the size parameters of the droplets or particles. For example, an average droplet or particle size and / or other parameters (e.g. a standard deviation) are determined. With these parameters, the measured current can be assigned to an analyte quantity (or concentration).

The at least one parameter can also comprise a total liquid flow from which the droplets are generated. This total flow can e.g. B. used in conjunction with a parameter of the droplet size to determine an analyte flow rate.

The at least one size parameter can comprise a mean value for the size of the particles or droplets and additionally or alternatively a breadth of a distribution for the size of the particles or droplets.

Additionally or alternatively, the at least one parameter can comprise at least one frequency parameter for a frequency of the particles or droplets. That is, a frequency parameter can provide information about the frequency with which particles or droplets pass a certain area or a certain volume.

Similar to the size parameter, this can be beneficial. For example, using the frequency parameter, either a size parameter of the droplets can be determined if the measuring unit is upstream of the drying unit and the total effluent flow supplied to the droplet generator is known, or it can be possible to determine a size parameter of the droplets if the measuring unit is located downstream of the drying unit and the current measured by the current measuring unit is taken into account. In the latter example it may also be possible to determine the analyte flow directly from the frequency parameter, i.e. H. without first determining the size parameter.

Thus, the determination of a frequency parameter can also make it possible to assign the measured current to an analyte amount (or concentration), whereby at least the effect of a varying particle size and thus the solvent dependency is reduced.

The frequency parameter can comprise an average value for the frequency of the particles or droplets.

That is, in embodiments of the present invention, in addition to the flow, at least one additional parameter of the particles or the droplets is determined, for example a size or frequency parameter.

These embodiments of the present invention thus not only provide the current, but also the additional parameter. By means of this additional parameter, for. For example, it can be determined whether the measured current was caused by many small particles or by fewer larger particles. It is understood that this z. B. can be achieved when measuring size or frequency parameters of the particles before reaching the current measuring unit.

However, it is not necessary to measure the size or frequency parameters of the particles. Instead, size or frequency parameters of the droplets can also be used. In general, it is understood that larger droplets (at a given analyte concentration) lead to larger particles, and droplets with a higher frequency lead to particles with a higher frequency. Thus, the size or frequency parameters of the droplets can also be used in connection with the flow in order to arrive at an improved estimate of the amount of analyte.

Additionally or alternatively, the at least one parameter can comprise at least one impulse parameter for the impulse of the particles or droplets, which can comprise an average value for the impulse of the particles or droplets in at least one direction.

Furthermore, the at least one parameter can comprise at least one speed parameter for the speed of the particles or droplets, which can comprise an average value for the speed of the particles or droplets in at least one direction.

In addition, the system can comprise a processing unit which is designed to receive and analyze the data from the measuring unit in order to determine the at least one parameter. In addition, the processing unit can be designed to determine an analyte flow rate based on the measured current and a subset of the at least one parameter.

That is to say, the processing unit can determine the at least one parameter based on the data provided by the measuring unit, e.g. B. the processing unit can determine an average value for the size of the particles or droplets. In addition, the processing unit can combine a subset of the at least one parameter with the current measured by the current measuring unit in order to estimate the corresponding analyte flow. It is understood that a subset includes at least one parameter. Furthermore, a sub-sentence of a sentence can also comprise the entire sentence, i. H. the subset of the at least one parameter can include all parameters.

In particular in embodiments in which the at least one parameter comprises at least one size parameter, the processing unit can be designed to determine an analyte flow rate based on the measured current and the at least one size parameter.

Alternatively, in embodiments in which the at least one parameter comprises at least one frequency parameter, the processing unit can be designed to determine an analyte flow rate based on the measured current and the at least one frequency parameter.

In addition, the processing unit can be designed to use machine learning methods in order to improve the analysis of the data from the measuring unit. That is to say, the processing unit can be designed to use algorithms using machine learning methods to improve the data analysis. Such machine learning methods can be, for example, monitored, unsupervised, reinforcement or feature learning.

The system can furthermore comprise a terminal and the processing unit can be designed to send the at least one parameter, the measured current and / or the analyte flow rate to the terminal. The terminal can be designed to convert at least a portion of the received data into a human-readable signal, which can be at least one chromatographic spectrum.

That is, the terminal can receive data such as B. receive the at least one parameter, the measured current and / or the analyte flow rate from the processing unit and convert at least a portion thereof into a human-readable signal. One such human readable signal can be a chromatographic spectrum, which typically indicates a time-resolved amount of analyte in the liquid being supplied to the system.

The processing unit can comprise at least one microprocessor, such as e.g. B. a central processing unit (CPU) and / or at least one circuit such. B. an application-specific integrated circuit (ASCI) or a field-programmable gate array (FPGA).

Furthermore, the system can comprise at least one memory, such as. B. at least one non-volatile storage device (e.g. a solid state drive (SSD)) and / or at least one volatile device (e.g. random access memory (RAM)).

The measuring unit can comprise an imaging device and the imaging device can comprise an image sensor. The image sensor can be a charge coupled device (CCD) or an active pixel sensor (API).

That is to say, the measuring unit can comprise a device for imaging the droplets or particles, for example a camera. Typically, the imaging device can comprise an image sensor which can be configured to provide the corresponding image data, such as e.g. B. a CCD or an API.

An angle between a direction of flow of the particles or droplets and an axis perpendicular to the image sensor of the imaging device can be in the range of 45 ° to 135 °, preferably 75 ° to 105 °, such as. B. 85 ° to 95 °.

The imaging device can further comprise optical elements that are designed to improve the imaging capability of the image sensor. That is, the imaging device can for example comprise a lens and / or a diaphragm in order to improve the imaging capability, such as e.g. B. the light intensity or the magnification of the image.

The measuring unit can furthermore comprise a light source. A light source can be, for example, an LED or a halogen lamp. In some embodiments, the light source can be a coherent laser light source. That is, the light source can be a source of coherent laser light, such as e.g. B. a semiconductor-based laser diode.

Furthermore, the light source can be designed to operate in a pulsed mode, and preferably the light source can be a stroboscope or a pulsed laser. That is, in contrast to continuously emitting light, the light source can emit light pulses at a given frequency.

The light source can also be designed to be modulated. That is, the light source can be designed to manipulate a property of the light beam, e.g. B. amplitude, polarization and / or phase. For example, the light source can be an optical modulator, such as. B. an absorbing modulator or a refractive modulator.

The light source can also comprise optical elements that are designed to modify the propagation of the light. Similar to the imaging device, such optical elements can include, for example, a lens, a diaphragm, a fiber or a waveguide. Optical elements can, for example, also contain glass fibers and waveguides, which can be advantageous in the case of certain spatial requirements within the system. Other optical elements can be, for example, a diffraction grating or a polarizer.

The measuring unit can comprise a control unit which is designed to ensure the synchronous operation of the imaging device and the light source. For example, if the light source is pulsed, the control unit can ensure that the imaging device images the droplets or particles synchronously with the light pulses.

The measuring unit can comprise a light sensor. That is, a sensor that is designed to detect light and provide a corresponding signal. The light sensor may be one of a photodiode, a photoresistor, or a phototransistor. In addition, the light sensor can also comprise optical elements that are designed to modify the propagation of the light.

The measuring unit can comprise a light barrier, which comprises the light source and the light sensor, wherein the light barrier can be designed to provide data on particles or droplets that pass through the light barrier. That is, the light source and the light sensor can be arranged such that the light beam is directed onto the light sensor. A particle or droplet passing the light beam can reduce or block the light reaching the light sensor. Thus, the light sensor can provide data about the particles or droplets passing through the sensor, e.g. B. the time at which a particle or droplet passes the detector.

The light barrier can be a one-way light barrier, i. H. the light source and the light sensor can be arranged opposite one another, so that the light emitted by the light source reaches the light sensor directly. Alternatively, the light barrier can also be a reflection light barrier, i. H. the light emitted by the light source can be reflected by a reflector before it reaches the light sensor.

The memory can include machine readable code. The machine-readable code can be designed to cause the processing unit to calculate the at least one parameter and / or the analyte flow rate.

The system can further comprise an ion trap, wherein the ion trap is arranged downstream of the charger and upstream of the current measuring unit. The ion trap can, for example, ions with high electrical mobility, such as. B. charged gas particles, eliminate.

Furthermore, the droplet generator can be designed to generate the droplets with a defined droplet generation frequency. That is, the droplet generator can generate the droplets at a frequency that can be controlled, for example, by a user.

Additionally or alternatively, the system can further comprise a flow control unit for controlling a flow towards the droplet generator. This means that the flow control unit can, for example, define a constant flow at a defined flow rate.

The drying unit comprises an end upstream of the drying unit and an end downstream of the drying unit. That is, the droplets generated by the droplet generator can enter the drying unit at the end upstream of the drying unit and, after passing through the drying unit, the resulting particles can leave the drying unit at the end downstream of the drying unit.

In embodiments in which the measuring unit is designed to observe the droplets, the measuring unit can be arranged downstream of the droplet generator and upstream of the end downstream of the drying unit. The determination of a property of the droplet can e.g. B. be advantageous for the following reason: It goes without saying that the particles (formed by the analyte) are typically significantly smaller than the droplets (formed by the analyte and the solvent). Thus, it may be easier to determine the properties of the larger droplets than the smaller particles, and less sophisticated equipment can be used.

Alternatively, in embodiments in which the measuring unit is designed to observe the particles, the measuring unit can be arranged downstream of the end located in front of the drying unit. Furthermore, the measuring unit can be arranged downstream of the end downstream of the drying unit. In addition, the measuring unit can be arranged upstream of the charger. Alternatively, the measuring unit can also be located in the charger.

The measuring unit can be arranged downstream of the charger. Furthermore, the measuring unit can be arranged downstream of the ion trap and upstream of the current measuring unit. This can be advantageous since the properties of the particles can thus be determined immediately before they enter the current measuring unit.

The processing unit can be designed such that the determined analyte flow rate is proportional to (V̅) ^-2/3 , where V̅ is an average volume of the particles or the droplets.

In other embodiments of the present invention it relates to a method for determining an analyte flow rate. The method includes providing a flow of a liquid comprising the analyte, creating droplets of the liquid, drying the droplets and thereby creating particles, charging the particles, and measuring a current generated by the charged particles. Furthermore, the method also includes determining at least one parameter of the particles or the droplets.

It will be understood that when reference is made herein to an amount of an analyte, the absolute amount of the analyte (e.g., expressed in kg, m ³ ), the concentration of the analyte in a solvent (e.g., expressed in kg / m ³ ) and also their time derivatives (such as an analyte flow, expressed in kg / s or m ³ / s, or a concentration, expressed in kg / (m ³ * s)) can be referred to. All of these statements indicate an amount of an analyte and all of these statements may be meant when reference is made herein to an amount of an analyte.

The method can include observing the particles and determining the at least one parameter based on this observation. Alternatively, the method can also include observing the droplets and determining the at least one parameter based on this observation.

Determining the at least one parameter can include determining at least one size parameter for a size of the particles or the droplets. Determining the at least one size parameter can include determining an average value for the size of the particles or droplets. The mean value can be, for example, the mean volume or the mean diameter of a particle or droplet. Additionally or alternatively, determining the at least one size parameter can include determining a width of a distribution for the size of the particles or droplets.

Furthermore, determining the at least one parameter can include determining at least one frequency parameter for a frequency of the particles or the droplets. Determining the at least one frequency parameter can include determining an average value for the frequency of the particles or droplets.

The determination of the at least one parameter can further comprise the determination of at least one pulse parameter for a pulse of the particles or droplets in at least one direction. Determining at least one pulse parameter can include determining an average value for the pulse of the particles or droplets.

Additionally or alternatively, the determination of the at least one parameter can further comprise the determination of at least one speed parameter for a speed of the particles or droplets in at least one direction. Determining the at least one speed parameter can include determining an average value for the speed of the particles.

Furthermore, the method can comprise the use of a system as described above.

In embodiments in which the system comprises an imaging device, the method can further comprise that the imaging device the images at intervals in a range from 1 ns to 10,000 ns, preferably 10 ns to 1,000 ns, further preferably 50 ns to 150 ns, such as z. B. 100 ns.

In embodiments where the system includes a light source, the method may further include pulsing the light source. Additionally or alternatively, the method can further comprise modulating the light source.

In embodiments in which the system comprises a control unit, the method may further comprise the control unit controlling the synchronous operation of the imaging device and the light source.

The method can further include the processing unit receiving and analyzing data from the measuring unit and the processing unit determining the parameters. Furthermore, the method can include the processing unit determining the analyte flow rate based on the measured current and a subset of the at least one parameter.

The method can further include that the processing unit uses machine learning methods for improved analysis of the data from the imaging device.

In embodiments in which the system includes a memory that includes machine-readable code, the machine-readable code stored in the memory of the processing unit can cause the processing unit to calculate the parameters.

In embodiments of the method, the system can take photos of the aerosol with the imaging device and it generates image data, analyzes the image data in the processing unit and determines the at least one parameter, and determines the analyte flow rate based on the measured current and a subset of the at least one parameter. Furthermore, the system can send the at least one parameter, the measured current and / or the analyte flow rate to the terminal.

The method may include steps wherein the system measures an angular intensity of light diffraction of the particles or droplets with the imaging device and generates image data, analyzes the image data in the processing unit and determines the at least one parameter, and the analyte flow rate based on the measured current and a subset of the at least one parameter is determined. Furthermore, the system can send the at least one parameter, the measured current and / or the analyte flow rate to the terminal.

The method may include the processing unit receiving flow data on the amount of liquid flow comprising the analyte that is provided to the droplet generator. That is, the processing unit can receive flow data on the liquid flow to the droplet generator. This flow data can for example be provided by a flow sensor or a user input.

The method may include steps wherein the system measures the droplets passing the light barrier and generates frequency data, analyzes the frequency data in the processing unit and determines the at least one frequency parameter, and the analyte flow rate based on the measured current, the flow data and the at least one Frequency parameters determined. Furthermore, the system can send the at least one frequency parameter, the measured current and / or the analyte flow rate to the terminal.

The method may include steps whereby the system measures the particles that pass the light barrier and generates frequency data, analyzes the frequency data in the processing unit and determines the at least frequency parameter, and determines the analyte flow rate based on the measured current and the at least one frequency parameter. Furthermore, the system can send the at least one frequency parameter, the measured current and / or the analyte flow rate to the terminal.

The system can be designed to carry out the method as described above.

The present invention can also relate to the use of a Charged Aerosol Detector System for the method according to the present invention.

It can be used in chromatography.

It can be used in liquid chromatography.

It can be used in high-performance liquid chromatography.

It can be used in ultra-high performance liquid chromatography.

That is to say, embodiments of the present invention relate to a charged aerosol detector system, the system being designed to determine a parameter of an aerosol within a CAD system.

In other words, in embodiments of the present technology, a parameter for a property of the particles or droplets is determined by the measuring unit, such as e.g. B. a size parameter or a frequency parameter. This parameter enables the measurement signal to be corrected, i.e. H. of the current, for different particle or droplet sizes and thus a more precise determination of the amount of analyte in a sample. As a result, the dependency of the result on the solvent used and the liquid flow rate can be eliminated or at least significantly reduced.

Furthermore, the technology described here can also be particularly suitable for use with solvent gradients, which are often used in chromatography. This means that the composition of the eluent changes during an analysis run. This can also be problematic as the size of the droplets (and particles) generated and thus the signal per analyte can depend on the solvent used. Since these problems are overcome by the present technology, the present technology can be particularly useful when using such solvent gradients.

The present technology is also defined by the following numbered embodiments.

• S1. Charged Aerosol Detector System, wobei das System Folgendes umfasst:
  • einen Tröpfchengenerator, der dazu ausgelegt ist, Tröpfchen zu erzeugen,
  • eine Trocknungseinheit, die dazu ausgelegt ist, die Tröpfchen zu trocknen und so Partikel zu erzeugen,
  • ein Ladegerät, das dazu ausgelegt ist, die Partikel aufzuladen,
  • eine Strommesseinheit, die dazu ausgelegt ist, einen von den geladenen Partikeln erzeugten Strom zu messen, und
  • eine Messeinheit, die dazu ausgelegt ist, Daten zum Bestimmen mindestens eines Parameters der Partikel oder der Tröpfchen bereitzustellen.
• S2. System nach der vorstehenden Ausführungsform, wobei die Messeinheit dazu ausgelegt ist, die Partikel zu beobachten und Daten zum Bestimmen des mindestens einen Parameters basierend auf dieser Beobachtung bereitzustellen.
• S3. System nach der vorletzten Ausführungsform, wobei die Messeinheit dazu ausgelegt ist, die Tröpfchen zu beobachten und Daten zum Bestimmen des mindestens einen Parameters basierend auf dieser Beobachtung bereitzustellen.
• S4. System nach einer der vorstehenden Ausführungsformen, wobei der mindestens eine Parameter mindestens einen Größenparameter für eine Größe der Partikel oder der Tröpfchen und vorzugsweise einen Gesamtflüssigkeitsfluss, aus dem die Tröpfchen gebildet werden, umfasst.
• S5. System nach der vorstehenden Ausführungsform, wobei der mindestens eine Größenparameter einen Mittelwert für die Größe der Partikel oder Tröpfchen umfasst.
• S6. System nach einer der 2 vorstehenden Ausführungsformen, wobei der mindestens eine Größenparameter eine Breite einer Verteilung für die Größe der Partikel oder Tröpfchen umfasst.
• S7. System nach einer der vorstehenden Ausführungsformen, wobei der mindestens eine Parameter mindestens einen Frequenzparameter für eine Frequenz der Partikel oder der Tröpfchen umfasst.
• S8. System nach der vorstehenden Ausführungsform, wobei der mindestens eine Frequenzparameter einen Mittelwert für die Frequenz der Partikel oder Tröpfchen umfasst.
• S9. System nach einer der vorstehenden Ausführungsformen, wobei der mindestens eine Parameter mindestens einen Impulsparameter für den Impuls der Partikel oder Tröpfchen umfasst.
• S10. System nach der vorstehenden Ausführungsform, wobei der mindestens eine Impulsparameter einen Mittelwert für den Impuls der Partikel oder Tröpfchen in mindestens einer Richtung umfasst.
• S11. System nach einer der vorstehenden Ausführungsformen, wobei der mindestens eine Parameter mindestens einen Geschwindigkeitsparameter für die Geschwindigkeit der Partikel oder Tröpfchen umfasst.
• S12. System nach der vorstehenden Ausführungsform, wobei der mindestens eine Geschwindigkeitsparameter einen Mittelwert für die Geschwindigkeit der Partikel oder Tröpfchen in mindestens einer Richtung umfasst.
• S13. System nach einer der vorstehenden Ausführungsformen, wobei das System eine Verarbeitungseinheit umfasst, die dazu ausgelegt ist, die Daten von der Messeinheit zu empfangen und zu analysieren, um den mindestens einen Parameter zu bestimmen.
• S14. System nach der vorstehenden Ausführungsform, wobei die Verarbeitungseinheit dazu ausgelegt ist, eine Analytflussmenge basierend auf dem gemessenen Strom und einem Teilsatz des mindestens einen Parameters zu bestimmen.
• S15. System nach der vorstehenden Ausführungsform und mit den Merkmalen von S4, wobei die Verarbeitungseinheit dazu ausgelegt ist, eine Analytflussmenge basierend auf dem gemessenen Strom und dem mindestens einen Größenparameter zu bestimmen.
• S16. System nach der vorletzten Ausführungsform mit den Merkmalen von S7, wobei die Verarbeitungseinheit dazu ausgelegt ist, eine Analytflussmenge basierend auf dem gemessenen Strom und dem mindestens einen Frequenzparameter zu bestimmen.
• S17. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen von S13, wobei die Verarbeitungseinheit dazu ausgelegt ist, maschinelle Lernverfahren einzusetzen, um die Analyse der Daten der Messeinheit zu verbessern.
• S18. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen von S14, wobei das System ferner ein Endgerät umfasst, und wobei die Verarbeitungseinheit dazu ausgelegt ist, den mindestens einen Parameter, den gemessenen Strom und/oder die Analytflussmenge an das Endgerät zu senden.
• S19. System nach der vorstehenden Ausführungsform, wobei das Endgerät dazu ausgelegt ist, mindestens einen Teil der empfangenen Daten in ein von Menschen lesbares Signal umzuwandeln.
• S20. System nach der vorstehenden Ausführungsform, wobei das vom Menschen lesbare Signal mindestens ein chromatografisches Spektrum ist.
• S21. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen von S13, wobei die Verarbeitungseinheit mindestens einen Mikroprozessor, wie z. B. eine Zentraleinheit (CPU) und/oder mindestens eine Schaltung, wie eine anwendungsspezifische integrierte Schaltung (ASCI) oder ein feldprogrammierbares Gate-Array (FPGA), umfasst.
• S22. System nach einer der vorstehenden Ausführungsformen, wobei das System mindestens einen Speicher, wie z. B. mindestens eine nichtflüchtige Speichervorrichtung (z. B. ein Solid-State-Laufwerk (SSD)) und/oder mindestens eine flüchtige Vorrichtung (z. B. Random-Access-Speicher (RAM)) umfasst.
• S23. System nach einer der vorstehenden Ausführungsformen, wobei die Messeinheit eine Bildgebungsvorrichtung umfasst.
• S24. System nach der vorstehenden Ausführungsform, wobei die Bildgebungsvorrichtung einen Bildsensor umfasst.
• S25. System nach der vorstehenden Ausführungsform, wobei der Bildsensor eine ladungsgekoppelte Vorrichtung (CCD) oder ein aktiver Pixel-Sensor (API) ist.
• S26. System nach einer der 2 vorstehenden Ausführungsformen, wobei ein Winkel zwischen einer Flussrichtung der Partikel oder Tröpfchen und einer Achse senkrecht zum Bildsensor der Bildgebungsvorrichtung im Bereich von 45° bis 135°, vorzugsweise 75° bis 105°, wie z. B. 85° bis 95°, liegt.
• S27. System nach einer der 3 vorstehenden Ausführungsformen, wobei die Bildgebungsvorrichtung ferner optische Elemente umfasst, die dazu ausgelegt sind, die Abbildungsfähigkeit des Bildsensors zu verbessern.
• S28. System nach einer der vorstehenden Ausführungsformen, wobei die Messeinheit ferner eine Lichtquelle umfasst.
• S29. System nach der vorstehenden Ausführungsform, wobei die Lichtquelle eine kohärente Laserlichtquelle ist.
• S30. System nach einer der 2 vorstehenden Ausführungsformen, wobei die Lichtquelle dazu ausgelegt ist, in einem gepulsten Modus zu arbeiten, und vorzugsweise wobei die Lichtquelle ein Stroboskop oder ein gepulster Laser ist.
• S31. System nach einer der 3 vorstehenden Ausführungsformen, wobei die Lichtquelle dazu ausgelegt ist, moduliert zu werden.
• S32. System nach einer der 4 vorstehenden Ausführungsformen, wobei die Lichtquelle optische Elemente umfasst, die dazu ausgelegt sind, die Ausbreitung von Licht zu modifizieren.
• S33. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen von S23 und S28, wobei die Messeinheit eine Steuereinheit umfasst, die dazu ausgelegt ist, den synchronen Betrieb der Bildgebungsvorrichtung und der Lichtquelle sicherzustellen.
• S34. System nach einer der vorstehenden Systemausführungsformen, wobei die Messeinheit einen Lichtsensor umfasst.
• S35. System nach der vorstehenden Ausführungsform, wobei der Lichtsensor eines von einer Fotodiode, einem Fotowiderstand oder einem Fototransistor ist.
• S36. System nach einer der zwei vorstehenden Ausführungsformen, wobei der Lichtsensor optische Elemente umfasst, die dazu ausgelegt sind, die Ausbreitung von Licht zu modifizieren.
• S37. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen von S28 und S34, wobei die Messeinheit eine Lichtschranke umfasst, die die Lichtquelle und den Lichtsensor umfasst, wobei die Lichtschranke dazu ausgelegt ist, Daten über Partikel oder Tröpfchen bereitzustellen, die die Lichtschranke passieren.
• S38. System nach der vorstehenden Ausführungsform, wobei die Lichtschranke eine Einweg-Lichtschranke ist.
• S39. System nach der vorletzten Ausführungsform, wobei die Lichtschranke eine Reflexions-Lichtschranke ist.
• S40. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen der Ausführungsform S22, wobei der Speicher maschinenlesbaren Code umfasst.
• S41. System nach der vorstehenden Ausführungsform und mit den Merkmalen von mindestens einer der Ausführungsformen S13 und S14, wobei der maschinenlesbare Code dazu ausgelegt ist, die Verarbeitungseinheit dazu zu veranlassen, den mindestens einen Parameter und/oder die Analytflussmenge zu berechnen.
• S42. System nach einer der vorstehenden Ausführungsformen, wobei das System ferner eine Ionenfalle umfasst, wobei die Ionenfalle dem Ladegerät nachgelagert und der Strommesseinheit vorgelagert angeordnet ist.
• S43. System nach einer der vorstehenden Ausführungsformen, wobei der Tröpfchengenerator dazu ausgelegt ist, die Tröpfchen mit einer definierten Tröpfchenerzeugungsfrequenz zu erzeugen.
• S44. System nach einer der vorstehenden Ausführungsformen, wobei das System ferner eine Flusssteuereinheit zum Steuern eines Flusses hin zum Tröpfchengenerator umfasst.
• S45. System nach einer der vorstehenden Ausführungsformen, wobei die Trocknungseinheit ein der Trocknungseinheit vorgelagertes Ende und ein der Trocknungseinheit nachgelagertes Ende umfasst.
• S46. System nach der vorstehenden Ausführungsform und mit den Merkmalen der Ausführungsform S3, wobei die Messeinheit dem Tröpfchengenerator nachgelagert und dem der Trocknungseinheit nachgelagerten Ende vorgelagert angeordnet ist.
• S47. System nach der vorletzten Ausführungsform und mit den Merkmalen der Ausführungsform S2, wobei die Messeinheit dem der Trocknungseinheit vorgelagerten Ende nachgelagert angeordnet ist.
• S48. System nach der vorstehenden Ausführungsform, wobei die Messeinheit dem der Trocknungseinheit nachgelagerten Ende nachgelagert angeordnet ist.
• S49. System nach der vorstehenden Ausführungsform, wobei die Messeinheit dem Ladegerät vorgelagert angeordnet ist.
• S50. System nach der vorletzten Ausführungsform, wobei die Messeinheit in dem Ladegerät angeordnet ist.
• S51. System nach der Ausführungsform S48, wobei die Messeinheit dem Ladegerät nachgelagert angeordnet ist.
• S52. System nach der vorstehenden Ausführungsform und mit den Merkmalen der Ausführungsform S42, wobei die Messeinheit der Ionenfalle nachgelagert und der Strommesseinheit vorgelagert angeordnet ist.
• S53. System nach einer der vorstehenden Ausführungsformen mit den Merkmalen der Ausführungsformen S5 und S14, wobei die Verarbeitungseinheit so ausgelegt ist, dass die bestimmte Analytflussmenge proportional zu (V̅)^-2/3 ist, wobei V̅ ein mittleres Volumen der Partikel oder der Tröpfchen ist.

System embodiments are referred to below. These embodiments are abbreviated by the letter “S” followed by the number. Whenever "system embodiments" are referred to in this document, these embodiments are meant.

• S1. Charged Aerosol Detector System, which system comprises:
  • a droplet generator designed to generate droplets,
  • a drying unit designed to dry the droplets and thus generate particles,
  • a charger designed to charge the particles,
  • a current measuring unit configured to measure a current generated by the charged particles, and
  • a measuring unit which is designed to provide data for determining at least one parameter of the particles or the droplets.
• S2. System according to the above embodiment, wherein the measuring unit is designed to observe the particles and to provide data for determining the at least one parameter based on this observation.
• S3. System according to the penultimate embodiment, wherein the measuring unit is designed to observe the droplets and to provide data for determining the at least one parameter based on this observation.
• S4. System according to one of the preceding embodiments, wherein the at least one parameter comprises at least one size parameter for a size of the particles or the droplets and preferably a total liquid flow from which the droplets are formed.
• S5. System according to the preceding embodiment, wherein the at least one size parameter comprises an average value for the size of the particles or droplets.
• S6. System according to one of the 2 preceding embodiments, wherein the at least one size parameter comprises a width of a distribution for the size of the particles or droplets.
• S7. System according to one of the preceding embodiments, wherein the at least one parameter comprises at least one frequency parameter for a frequency of the particles or the droplets.
• S8. System according to the preceding embodiment, wherein the at least one frequency parameter comprises an average value for the frequency of the particles or droplets.
• S9. System according to one of the preceding embodiments, wherein the at least one parameter comprises at least one pulse parameter for the pulse of the particles or droplets.
• S10. System according to the preceding embodiment, wherein the at least one pulse parameter comprises an average value for the pulse of the particles or droplets in at least one direction.
• S11. System according to one of the preceding embodiments, wherein the at least one parameter comprises at least one speed parameter for the speed of the particles or droplets.
• S12. System according to the preceding embodiment, wherein the at least one speed parameter comprises an average value for the speed of the particles or droplets in at least one direction.
• S13. System according to one of the preceding embodiments, wherein the system comprises a processing unit which is designed to receive and analyze the data from the measuring unit in order to determine the at least one parameter.
• S14. System according to the preceding embodiment, wherein the processing unit is configured to determine an analyte flow rate based on the measured current and a subset of the at least one parameter.
• S15. System according to the above embodiment and having the features of S4, wherein the processing unit is designed to determine an analyte flow rate based on the measured current and the at least one size parameter.
• S16. System according to the penultimate embodiment having the features of S7, wherein the processing unit is designed to determine an analyte flow rate based on the measured current and the at least one frequency parameter.
• S17. System according to one of the preceding embodiments having the features of S13, wherein the processing unit is designed to use machine learning methods in order to improve the analysis of the data from the measuring unit.
• S18. System according to one of the preceding embodiments with the features of S14, wherein the system further comprises a terminal, and wherein the processing unit is designed to send the at least one parameter, the measured current and / or the analyte flow rate to the terminal.
• S19. System according to the preceding embodiment, wherein the terminal is designed to convert at least part of the received data into a human-readable signal.
• S20. The system of the previous embodiment, wherein the human readable signal is at least one chromatographic spectrum.
• S21. System according to one of the preceding embodiments with the features of S13, wherein the processing unit has at least one microprocessor, such as. B. a central processing unit (CPU) and / or at least one circuit, such as an application-specific integrated circuit (ASCI) or a field-programmable gate array (FPGA).
• S22. System according to one of the preceding embodiments, wherein the system comprises at least one memory, such as e.g. B. comprises at least one non-volatile storage device (e.g. a solid state drive (SSD)) and / or at least one volatile device (e.g. random access memory (RAM)).
• S23. System according to one of the preceding embodiments, wherein the measuring unit comprises an imaging device.
• S24. The system of the previous embodiment, wherein the imaging device comprises an image sensor.
• S25. The system of the previous embodiment, wherein the image sensor is a charge coupled device (CCD) or an active pixel sensor (API).
• S26. System according to one of the 2 preceding embodiments, wherein an angle between a direction of flow of the particles or droplets and an axis perpendicular to the image sensor of the imaging device is in the range from 45 ° to 135 °, preferably 75 ° to 105 °, e.g. B. 85 ° to 95 °.
• S27. System according to one of the 3 preceding embodiments, wherein the imaging device further comprises optical elements which are designed to improve the imaging capability of the image sensor.
• S28. System according to one of the preceding embodiments, wherein the measuring unit further comprises a light source.
• S29. The system of the previous embodiment, wherein the light source is a coherent laser light source.
• S30. System according to one of the 2 preceding embodiments, wherein the light source is adapted to operate in a pulsed mode, and preferably wherein the light source is a stroboscope or a pulsed laser.
• S31. System according to one of the 3 preceding embodiments, wherein the light source is designed to be modulated.
• S32. System according to one of the 4 preceding embodiments, wherein the light source comprises optical elements which are designed to modify the propagation of light.
• S33. System according to one of the preceding embodiments with the features of S23 and S28, wherein the measuring unit comprises a control unit which is designed to ensure the synchronous operation of the imaging device and the light source.
• S34. System according to any of the preceding system embodiments, wherein the measuring unit comprises a light sensor.
• S35. The system according to the above embodiment, wherein the light sensor is one of a photodiode, a photoresistor or a phototransistor.
• S36. System according to one of the two preceding embodiments, wherein the light sensor comprises optical elements which are designed to modify the propagation of light.
• S37. System according to one of the preceding embodiments with the features of S28 and S34, wherein the measuring unit comprises a light barrier which comprises the light source and the light sensor, the light barrier being designed to provide data on particles or droplets that pass through the light barrier.
• S38. System according to the previous embodiment, wherein the light barrier is a one-way light barrier.
• S39. System according to the penultimate embodiment, wherein the light barrier is a reflection light barrier.
• S40. System according to one of the preceding embodiments having the features of the embodiment S22 wherein the memory comprises machine readable code.
• S41. System according to the preceding embodiment and having the features of at least one of the embodiments S13 and S14 wherein the machine-readable code is designed to cause the processing unit to calculate the at least one parameter and / or the analyte flow rate.
• S42. System according to one of the preceding embodiments, wherein the system further comprises an ion trap, wherein the ion trap is arranged downstream of the charger and upstream of the current measuring unit.
• S43. System according to one of the preceding embodiments, wherein the droplet generator is designed to generate the droplets with a defined droplet generation frequency.
• S44. The system according to any of the preceding embodiments, wherein the system further comprises a flow control unit for controlling a flow towards the droplet generator.
• S45. System according to one of the preceding embodiments, wherein the drying unit comprises an end upstream of the drying unit and an end downstream of the drying unit.
• S46. System according to the above embodiment and having the features of the embodiment S3 , wherein the measuring unit is arranged downstream of the droplet generator and upstream of the end downstream of the drying unit.
• S47. System according to the penultimate embodiment and having the features of the embodiment S2 , wherein the measuring unit is arranged downstream of the end upstream of the drying unit.
• S48. System according to the preceding embodiment, wherein the measuring unit is arranged downstream of the end downstream of the drying unit.
• S49. System according to the preceding embodiment, wherein the measuring unit is arranged upstream of the charger.
• S50. System according to the penultimate embodiment, wherein the measuring unit is arranged in the charger.
• S51. System according to the embodiment S48 , wherein the measuring unit is arranged downstream of the charger.
• S52. System according to the above embodiment and having the features of the embodiment S42 , wherein the measuring unit is arranged downstream of the ion trap and upstream of the current measuring unit.
• S53. System according to one of the preceding embodiments having the features of the embodiments S5 and S14 , wherein the processing unit is designed such that the determined analyte flow rate is proportional to (V̅) ^-2/3 , where V̅ is an average volume of the particles or the droplets.

• M1. Verfahren zum Bestimmen einer Menge eines Analytflusses, wobei das Verfahren Folgendes umfasst:
  • Bereitstellen eines Flusses einer Flüssigkeit, die den Analyten umfasst, Erzeugen von Tröpfchen der Flüssigkeit,
  • Trocknen der Tröpfchen und somit Erzeugen von Partikeln, Aufladen der Partikel,
  • Messen eines von den geladenen Partikeln erzeugten Stroms und Bestimmen mindestens eines Parameters der Partikel oder der Tröpfchen.
  Es versteht sich, dass, wenn hierin auf eine Menge eines Analyten Bezug genommen wird, auf die absolute Menge des Analyten (z. B. ausgedrückt in kg, m³), die Konzentration des Analyten in einem Lösemittel (z. B. ausgedrückt in kg/m³) und auch auf deren Zeitderivate (wie z. B. einen Analytfluss, ausgedrückt in kg/s oder m³/s, oder eine Konzentration, ausgedrückt in kg/(m³*s)) Bezug genommen werden kann. Alle diese Angaben geben eine Menge eines Analyten an und alle diese Angaben können gemeint sein, wenn hierin auf eine Menge eines Analyten Bezug genommen wird.
• M2. Verfahren nach der vorstehenden Verfahrensausführungsform, wobei das Verfahren das Beobachten der Partikel und das Bestimmen des mindestens einen Parameters basierend auf dieser Beobachtung umfasst.
• M3. Verfahren nach der vorletzten Verfahrensausführungsform, wobei das Verfahren das Beobachten der Tröpfchen und das Bestimmen des mindestens einen Parameters basierend auf dieser Beobachtung umfasst.
• M4. Verfahren nach einer der vorstehenden Verfahrensausführungsformen, wobei das Bestimmen des mindestens einen Parameters das Bestimmen mindestens eines Größenparameters für eine Größe der Partikel oder der Tröpfchen umfasst.
• M5. Verfahren nach dem vorstehenden Verfahren, wobei das Bestimmen des mindestens eines Größenparameters das Bestimmen eines Mittelwerts für die Größe der Partikel oder Tröpfchen umfasst.
• M6. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen von M4, wobei das Bestimmen von mindestens einem Größenparameter das Bestimmen einer Breite einer Verteilung für die Größe der Partikel oder Tröpfchen umfasst.
• M7. Verfahren nach einer der vorstehenden Verfahrensausführungsformen, wobei das Bestimmen des mindestens einen Parameters das Bestimmen von mindestens einem Frequenzparameter für eine Frequenz der Partikel oder der Tröpfchen umfasst.
• M8. Verfahren nach der vorstehenden Verfahrensausführungsform, wobei das Bestimmen des mindestens einen Frequenzparameters das Bestimmen eines Mittelwerts für die Frequenz der Partikel oder Tröpfchen umfasst.
• M9. Verfahren nach einer der vorstehenden Verfahrensausführungsformen, wobei das Bestimmen des mindestens einen Parameters ferner das Bestimmen von mindestens einem Impulsparameter für einen Impuls der Partikel oder Tröpfchen in mindestens einer Richtung umfasst.
• M10. Verfahren nach der vorstehenden Ausführungsform, wobei das Bestimmen mindestens eines Impulsparameters das Bestimmen eines Mittelwerts für den Impuls der Partikel oder Tröpfchen umfasst.
• M11. Verfahren nach einer der vorstehenden Verfahrensausführungsformen, wobei das Bestimmen des mindestens einen Parameters ferner das Bestimmen von mindestens einem Geschwindigkeitsparameter für eine Geschwindigkeit der Partikel oder Tröpfchen in mindestens einer Richtung umfasst.
• M12. Verfahren nach der vorstehenden Ausführungsform, wobei das Bestimmen des mindestens eines Geschwindigkeitsparameters das Bestimmen eines Mittelwerts für die Geschwindigkeit der Partikel umfasst.
• M13. Verfahren nach einer der vorstehenden Verfahrensausführungsformen, wobei das Verfahren das Verwenden eines Systems nach einer der vorstehenden Systemausführungsformen umfasst.
• M14. Verfahren nach der vorstehenden Verfahrensausführungsform, wobei das System die Merkmale der Ausführungsform S23 umfasst, wobei das Verfahren ferner umfasst, dass die Bildgebungsvorrichtung Bilder in Intervallen in einem Bereich von 1 ns bis 10.000 ns, vorzugsweise 10 ns bis 1.000 ns, ferner vorzugsweise 50 ns bis 150 ns, wie z. B. 100 ns, aufnimmt.
• M15. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsform M13, wobei das System die Merkmale der Ausführungsform S30 umfasst, wobei das Verfahren ferner das Pulsieren der Lichtquelle umfasst.
• M16. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen von M13, wobei das System die Merkmale der Ausführungsform S31 umfasst, wobei das Verfahren ferner das Modulieren der Lichtquelle umfasst.
• M17. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsform M13, wobei das System die Merkmale der Systemausführungsform S33 umfasst, wobei das Verfahren ferner umfasst, dass die Steuereinheit den Synchronbetrieb der Bildgebungsvorrichtung und der Lichtquelle steuert.
• M18. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsform M13, wobei das System die Merkmale der Systemausführungsform S13 umfasst, wobei das Verfahren ferner umfasst, dass die Verarbeitungseinheit Daten von der Messeinheit empfängt und analysiert und die Verarbeitungseinheit den mindestens einen Parameter bestimmt.
• M19. Verfahren nach den vorstehenden Verfahrensausführungsformen, wobei das Verfahren umfasst, dass die Verarbeitungseinheit die Analytflussmenge basierend auf dem gemessenen Strom und einem Teilsatz des mindestens einen Parameters bestimmt.
• M20. Verfahren nach der vorstehenden Verfahrensausführungsform, wobei das Verfahren ferner umfasst, dass die Verarbeitungseinheit maschinelle Lernverfahren zur verbesserten Analyse der Daten von der Bildgebungsvorrichtung verwendet.
• M21. Verfahren nach einer der 2 vorstehenden Verfahrensausführungsformen, wobei das System die Merkmale der Ausführungsform S40 umfasst, wobei der im Speicher der Verarbeitungseinheit gespeicherte maschinenlesbare Code die Verarbeitungseinheit dazu veranlasst, die Parameter zu berechnen.
• M22. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsform M13, wobei das System die Merkmale der Systemausführungsformen S14, S18 und S23 umfasst, wobei das System mit der Bildgebungsvorrichtung Fotos des Aerosols aufnimmt und Bilddaten erzeugt; die Bilddaten in der Verarbeitungseinheit analysiert und den mindestens einen Parameter bestimmt; die Analytflussmenge basierend auf dem gemessenen Strom und einem Teilsatz des mindestens einen Parameters bestimmt; und den mindestens einen Parameter, den gemessenen Strom und/oder die Analytflussmenge an das Endgerät sendet.
• M23. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsform M13, wobei das System die Merkmale der Systemausführungsformen S14, S18 und S23 umfasst, wobei das System eine Winkelintensität der Lichtbeugung der Partikel oder Tröpfchen mit der Bildgebungsvorrichtung misst und Bilddaten erzeugt; die Bilddaten in der Verarbeitungseinheit analysiert und den mindestens einen Parameter bestimmt; die Analytflussmenge basierend auf dem gemessenen Strom und einem Teilsatz des mindestens einen Parameters bestimmt; und den mindestens einen Parameter, den gemessenen Strom und/oder die Analytflussmenge an das Endgerät sendet.
• M24. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen von M13, wobei das System die Merkmale der Systemausführungsform S13 umfasst, wobei das Verfahren umfasst, dass die Verarbeitungseinheit Flussdaten über die Menge des Flüssigkeitsflusses empfängt, die den Analyten umfasst, der dem Tröpfchengenerator zugeführt wird.
• M25. Verfahren nach der vorstehenden Verfahrensausführungsform mit den Merkmalen von M3, M7 und M13, wobei das System die Merkmale der Systemausführungsformen S14, S18 und S37 umfasst, wobei das System die Tröpfchen, die die Lichtschranke passieren, misst und Frequenzdaten erzeugt; die Frequenzdaten in der Verarbeitungseinheit analysiert und den mindestens einen Frequenz-Parameter bestimmt; die Analytflussmenge basierend auf dem gemessenen Strom, den Flussdaten und dem mindestens einen Frequenzparameter bestimmt; und den mindestens einen Frequenzparameter, den gemessenen Strom und/oder die Analytflussmenge an das Endgerät sendet.
• M26. Verfahren nach einer der vorstehenden Verfahrensausführungsformen mit den Merkmalen der Ausführungsformen M2, M7 und M13, wobei das System die Merkmale der Systemausführungsformen S14, S18 und S37 umfasst, wobei das System die Partikel, die die Lichtschranke passieren, misst und Frequenzdaten erzeugt; die Frequenzdaten in der Verarbeitungseinheit analysiert und den mindestens Frequenzparameter bestimmt; die Analytflussmenge basierend auf dem gemessenen Strom und dem mindestens einen Frequenzparameter bestimmt; und den mindestens einen Frequenzparameter, den gemessenen Strom und/oder die Analytflussmenge an das Endgerät sendet.
• S54. System nach einer der vorstehenden Systemausführungsformen, wobei das System dazu ausgelegt ist, das Verfahren nach einer der vorstehenden Verfahrensausführungsformen auszuführen. Nachstehend wird auf Verwendungsausführungsformen Bezug genommen. Diese Ausführungsformen werden durch den Buchstaben „U“ mit nachfolgender Nummer abgekürzt. Wann immer in diesem Schriftstück auf „Verwendungsausführungsformen“ Bezug genommen wird, sind diese Ausführungsformen gemeint.
• U1. Verwendung des Charged Aerosol Detector Systems nach einer der vorstehenden Systemausführungsformen in einem Verfahren nach einer der vorstehenden Verfahrensausführungsformen.
• U2. Verwendung nach der vorstehenden Ausführungsform in der Chromatografie.
• U3. Verwendung nach der vorstehenden Ausführungsform in der Flüssigkeitschromatografie.
• U4. Verwendung nach der vorstehenden Ausführungsform in der Hochleistungs-Flüssigkeitschromatografie.
• U5. Verwendung nach der vorstehenden Ausführungsform in der Ultrahochleistungs-Flüssigkeitschromatografie erfolgt.

Reference is made below to method embodiments. These embodiments are abbreviated by the letter “M” followed by the number. Whenever "method embodiments" are referred to in this document, these embodiments are meant.

• M1. A method of determining an amount of analyte flow, the method comprising:
  • Providing a flow of a liquid comprising the analyte, generating droplets of the liquid,
  • Drying the droplets and thus creating particles, charging the particles,
  • Measuring a current generated by the charged particles and determining at least one parameter of the particles or the droplets.
  It will be understood that when reference is made herein to an amount of an analyte, the absolute amount of the analyte (e.g., expressed in kg, m ³ ), the concentration of the analyte in a solvent (e.g., expressed in kg / m ³ ) and also their time derivatives (such as an analyte flow, expressed in kg / s or m ³ / s, or a concentration, expressed in kg / (m ³ * s)) can be referred to. All of these statements indicate an amount of an analyte and all of these statements may be meant when reference is made herein to an amount of an analyte.
• M2. Method according to the above method embodiment, wherein the method comprises observing the particles and determining the at least one parameter based on this observation.
• M3. Method according to the penultimate method embodiment, wherein the method comprises observing the droplets and determining the at least one parameter based on this observation.
• M4. Method according to one of the preceding method embodiments, wherein determining the at least one parameter comprises determining at least one size parameter for a size of the particles or the droplets.
• M5. Method according to the above method, wherein determining the at least one size parameter comprises determining an average value for the size of the particles or droplets.
• M6. Method according to one of the above method embodiments with the features of M4, wherein the determination of at least one size parameter comprises the determination of a width of a distribution for the size of the particles or droplets.
• M7. Method according to one of the preceding method embodiments, wherein the determination of the at least one parameter comprises the determination of at least one frequency parameter for a frequency of the particles or the droplets.
• M8. Method according to the above method embodiment, wherein determining the at least one frequency parameter comprises determining a mean value for the frequency of the particles or droplets.
• M9. Method according to one of the preceding method embodiments, wherein determining the at least one parameter further comprises determining at least one pulse parameter for a pulse of the particles or droplets in at least one direction.
• M10. Method according to the preceding embodiment, wherein determining at least one pulse parameter comprises determining a mean value for the pulse of the particles or droplets.
• M11. Method according to one of the preceding method embodiments, wherein determining the at least one parameter further comprises determining at least one speed parameter for a speed of the particles or droplets in at least one direction.
• M12. Method according to the preceding embodiment, wherein determining the at least one speed parameter comprises determining an average value for the speed of the particles.
• M13. Method according to one of the preceding method embodiments, the method comprising using a system according to one of the preceding system embodiments.
• M14. Method according to the above method embodiment, wherein the system has the features of the embodiment S23 wherein the method further comprises that the imaging device images at intervals in a range of 1 ns to 10,000 ns, preferably 10 ns to 1,000 ns, further preferably 50 ns to 150 ns, such as. B. 100 ns.
• M15. Method according to one of the above method embodiments with the features of the embodiment M13 , the system having the features of the embodiment S30 wherein the method further comprises pulsing the light source.
• M16. Method according to one of the above method embodiments having the features of M13, wherein the system has the features of the embodiment S31 wherein the method further comprises modulating the light source.
• M17. Method according to one of the above method embodiments with the features of the embodiment M13 , the system having the characteristics of the system embodiment S33 wherein the method further comprises that the control unit controls the synchronous operation of the imaging device and the light source.
• M18. Method according to one of the above method embodiments with the features of the embodiment M13 , the system having the characteristics of the system embodiment S13 wherein the method further comprises that the processing unit receives and analyzes data from the measuring unit and the processing unit determines the at least one parameter.
• M19. Method according to the above method embodiments, wherein the method comprises that the processing unit determines the analyte flow rate based on the measured current and a subset of the at least one parameter.
• M20. Method according to the above method embodiment, wherein the method further comprises that the processing unit uses machine learning methods for improved analysis of the data from the imaging device.
• M21. Method according to one of the 2 above method embodiments, wherein the system has the features of the embodiment S40 wherein the machine-readable code stored in the memory of the processing unit causes the processing unit to calculate the parameters.
• M22. Method according to one of the above method embodiments with the features of the embodiment M13 , the system having the characteristics of the system embodiments S14 , S18 and S23 wherein the system with the imaging device takes photos of the aerosol and generates image data; analyzes the image data in the processing unit and determines the at least one parameter; determine the analyte flow rate based on the measured current and a subset of the at least one parameter; and sends the at least one parameter, the measured current and / or the analyte flow rate, to the terminal device.
• M23. Method according to one of the above method embodiments with the features of the embodiment M13 , the system having the characteristics of the system embodiments S14 , S18 and S23 wherein the system measures an angular intensity of light diffraction of the particles or droplets with the imaging device and generates image data; analyzes the image data in the processing unit and determines the at least one parameter; determine the analyte flow rate based on the measured current and a subset of the at least one parameter; and sends the at least one parameter, the measured current and / or the analyte flow rate, to the terminal device.
• M24. Method according to one of the above method embodiments having the features of M13, wherein the system has the features of the system embodiment S13 wherein the method comprises the processing unit receiving flow data on the amount of the liquid flow comprising the analyte being delivered to the droplet generator.
• M25. Method according to the above method embodiment with the features of M3, M7 and M13, wherein the system has the features of the system embodiments S14 , S18 and S37 wherein the system measures the droplets passing the photoelectric switch and generates frequency data; the frequency data is analyzed in the processing unit and the at least one frequency parameter is determined; determine the analyte flow rate based on the measured current, the flow data and the at least one frequency parameter; and sends the at least one frequency parameter, the measured current and / or the analyte flow rate to the terminal.
• M26. Method according to one of the above method embodiments with the features of the embodiments M2 , M7 and M13 , the system having the characteristics of the system embodiments S14 , S18 and S37 wherein the system measures the particles passing the light barrier and generates frequency data; the frequency data is analyzed in the processing unit and the at least frequency parameter is determined; determine the analyte flow rate based on the measured current and the at least one frequency parameter; and sends the at least one frequency parameter, the measured current and / or the analyte flow rate to the terminal.
• S54. System according to one of the preceding system embodiments, the system being designed to carry out the method according to one of the preceding method embodiments. Reference is made below to use embodiments. These embodiments are abbreviated by the letter “U” followed by a number. Whenever "use embodiments" are referred to in this document, these embodiments are meant.
• U1. Use of the Charged Aerosol Detector System according to one of the above system embodiments in a method according to one of the above method embodiments.
• U2. Use according to the above embodiment in chromatography.
• U3. Use according to the above embodiment in liquid chromatography.
• U4. Use according to the above embodiment in high-performance liquid chromatography.
• U5. Use according to the above embodiment takes place in ultra-high-performance liquid chromatography.

• 1 zeigt ein CAD-System nach dem Stand der Technik, wobei Komponenten dieses Systems auch in Ausführungsformen der vorliegenden Erfindung verwendet werden können;
• 2 zeigt ein CAD-System nach Ausführungsformen der vorliegenden Erfindung;
• 3 zeigt ein CAD-System nach Ausführungsformen der vorliegenden Erfindung;
• 4 zeigt eine Schemazeichnung einer Messeinheit;
• 5 zeigt eine Schemazeichnung der Lichtschranke in zwei verschiedenen Konfigurationen;
• 6A zeigt die Abhängigkeit des Stroms von dem Analytfluss und der Partikelgröße; und
• 6B und 6C zeigen die Abhängigkeit des Stroms von dem Analytfluss bzw. von der Partikelgröße.

Embodiments of the present invention will now be described with reference to the accompanying drawings. These embodiments are only intended to give examples of the present invention, but not to limit them.

• 1 Figure 3 shows a prior art CAD system, components of which system may also be used in embodiments of the present invention;
• 2 Figure 3 shows a CAD system in accordance with embodiments of the present invention;
• 3 Figure 3 shows a CAD system in accordance with embodiments of the present invention;
• 4th shows a schematic drawing of a measuring unit;
• 5 shows a schematic drawing of the light barrier in two different configurations;
• 6A shows the dependence of the current on the analyte flow and the particle size; and
• 6B and 6C show the dependence of the current on the analyte flow or on the particle size.

It should be noted that not all drawings have all reference symbols. Instead, some of the reference numbers have been omitted in some drawings for reasons of space and simplicity of illustration. Embodiments of the present invention will now be described with reference to the accompanying drawings.

Throughout the description, the term “in the direction of flow” is used. This is the direction in which a liquid or an aerosol moves through the various phases of a CAD system. In the in 4th The illustrated embodiment is the flow direction from left to right, ie the drying unit 2005 (which also acts as a drying line 2005 is further down the flow direction than the imaging device 102 . An element arranged further forward in the flow direction can also be referred to as “forward” or “downstream”. That is, the drying line 2005 is the imaging device 102 downstream. Similarly, the opposite term “upstream” refers to an element that is closer to the origin of the flow than another element. That is, the imaging device 102 is the drying line 2005 upstream.

In general, an HPLC effluent can comprise a liquid system which can further comprise at least one eluent and at least one sample. The HPLC effluent can also be referred to as HPLC liquid or simply as effluent or liquid. In the following mostly only the term “liquid” is used. It should be understood that the liquid typically comprises the sample to be analyzed and at least one solvent. In many cases it includes the sample and a mixed solvent.

In CAD systems, an HPLC effluent can first be converted into an aerosol. The eluent of the aerosol droplets is evaporated so that the analyte to be measured is converted into a secondary, mostly dry aerosol. This aerosol can then be electrically charged. The charge of the aerosol can be measured in an ammeter. The measured current can be a measure of the amount of analyte. One difference to the widely used UV detectors is that the CAD method does not require any chromophores in the analyte. This detector is therefore called a universal detector.

1 shows a CAD system 1000 According to the state of the art. The charged aerosol detector can also be used as a system 1000 are designated. Simply put, the system includes 1000 an effluent inlet 1001 for guiding the liquid and a gas inlet 1002 to supply of the system 1000 with a gas. The gas can be an inert gas, such as. B. Nitrogen (N ₂ ). In some embodiments, the CAD system 1000 be used in an HPLC system and actually be part of an HPLC system. In such systems, the effluent inlet 1001 also as HPLC inlet 1001 because it can take up effluent from an HPLC column. It goes without saying, however, that the technology described here is not restricted to an application in HPLC and can actually also be used in other applications.

The gas inlet 1002 can also be used as an inert gas inlet 1002 are designated. This can be used for safety reasons, ie not to produce a flammable (or explosive) composition. But it may also be possible to use other gases, such as. B. air to use. The HPLC inlet 1001 can also be used as HPLC column effluent inlet 1001 or simply as a sample inlet 1001 are designated. The system 1000 further comprises an atomizer 1003 (as an example of a droplet generator) for generating a spray of fine droplets of a liquid flowing through the sample inlet 1001 is fed.

Simply put, an HPLC effluent becomes an atomizer 1003 via an effluent inlet 1001 fed. At the same time the atomizer will 1003 via a gas inlet 1002 fed with a gas. Simply put, the atomizer comprises 1003 a capillary inlet that connects to the HPLC inlet 1001 and one coaxial with one gas inlet 1002 fed inert gas flow is connected. The atomizer 1003 creates a spray of fine droplets of an HPLC effluent, ie an aerosol.

The system also includes 1000 a spray chamber 1004 who have favourited the spray in the atomizer 1003 fine droplets formed. As soon as a spray mist flows into the spray chamber 1004 is directed, the droplets formed move over a certain distance. Droplets of sufficiently small size, ie small mass, are drawn into the upper area of the spray chamber by the gas flow 1004 carried away. The droplets become a drying pipe 1005 that also acts as a drying tube 1005 , Evaporation pipe 1005 or evaporation line 1005 can be designated. The droplets that are not in the top area inside the spray chamber 1004 that are droplets that are not small enough to move from the gas to the top of the spray chamber 1004 to be transported hit the rear wall of the spray chamber 1004 . These relatively large droplets thus collect as a liquid on the rear wall of the spray chamber 1004 , also known as an impactor. Thus, relatively large droplets become part of the liquid formed on the impactor and the liquid flows downwards and eventually runs out of the spray chamber 1004 in a sequence 1006 away. The smaller droplets that are in the top of the spray chamber 1004 can get through the drying tube 1005 which allows the evaporation of the remaining volatile components of the droplets, e.g. B. the evaporation of remaining solvent. The evaporation of the remaining volatile fraction of the droplets can be achieved, for example, by heating the drying tube 1005 can be achieved.

In other words, they are from the atomizer 1003 formed droplets of a spray chamber 1004 supplied, in which the smaller size droplets make their way to the top of the spray chamber 1004 can travel to then pass through a heated evaporation section, which acts as a drying tube 1005 is called to arrive. When passing through the drying tube 1005 the droplets are dried by eliminating the volatile residual liquid, ie the solvent. Thus, dry solid particles are generated which the drying tube 1005 leaving. Generally it is understood that the purpose of the drying tube 1005 consists in removing the solvent. Most substances form at the end of the drying tube when all of the solvent is removed 1005 dry particles (that is, they are solid). However, depending on the details of the phase transition, some substances (even if all of the solvent has been removed) may also be in the liquid phase. For the sake of simplicity, these substances can also be summarized under the term “particles” when the solvent has been removed after the drying tube.

After drying, the particles become a mixing chamber 1008 fed through a gas inlet 1002 is also supplied with an inert gas flow. Before entering the mixing chamber 1008 becomes the inert gas with an ionizer 1007 electrically charged, ie ionized, and the mixing chamber 1008 supplied in excess. It should be understood that the ionizer 1007 and the mixing chamber 1008 together represent an example of a charger designed to charge the particles generated by the drying of the droplets. The charged (inert) gas interacts with the particles in the charger to form electrically charged particles, which together with the excess charged gas lead to a collector 1010 be directed. Before entering the collector 1010 the charged particles and the excess charged gas pass through an ion trap 1009 , which eliminates ions with high electrical mobility, ie the ion trap 1009 removes charged gas particles (e.g. charged N ₂ particles) and also other small charged particles (e.g. particles with a size of up to 6 nm). Of the collector 1010 is an ammeter, so it can also be used as an ammeter 1010 or simply as an ammeter 1010 are designated. The ammeter then transmits 1010 a signal to a terminal 1011 . The one from the ammeter 1010 emitted signal is the result of the discharge of the charged particles. The intensity of the signal is proportional to the amount of charge contained in the particles, which is related to the amount of analyte contained in the particles (and thus also in the droplets).

In short, the charged aerosol detector works 1000 by having an (inert) gas flow (injected through a gas inlet 1002 ) by means of an atomizer 1003 a liquid supplied from an effluent inlet 1001 is fed to generate droplets. Unsuitable droplets will be in the drain 1006 and then the remaining solvent is drained through an evaporation line 1005 evaporates. In a mixing chamber 1008 of the charger, the particles are removed from the ionizer by means of one 1007 supplied ionized gas is charged with a surface charge and particles with high electrical mobility are trapped by an ion trap 1009 eliminated. Finally, the charged particles are measured by an ammeter 1010 is measured and the measured charge is related to the amount of analyte in the injected sample and displayed on a terminal 1011 expressed as a chromatographic spectrum.

In simpler terms, it uses the CAD system 1000 a pneumatic nebulizer 1003 to generate an aerosol from a solvent comprising a sample. This aerosol is also known as the primary aerosol. This primary aerosol is then placed in a drying tube 1005 dried, which can optionally be heated to create a secondary aerosol, typically comprising solid particles. The transport of the aerosol through this drying tube 1005 is through that through the gas inlet 1002 supplied gas from the nebulizer 1003 influenced. At the end of the drying tube 1005 the solvent has evaporated. Then the secondary aerosol is z. B. by means of charged nitrogen ions in a mixing chamber 1008 of a charger. This charging process is essentially a diffusion charging process. The charged particles are then placed in a filter ammeter 1010 discharged, whereby the discharge current is measured. The filter ammeter 1010 upstream is an ion trap 1009 arranged. This ion trap 1009 removes charged nitrogen ions from the gas flow, as these are not in the ammeter 1010 should be measured. Another component is one in the spray chamber 1004 arranged impactor, also known as the back wall of the spray chamber 1004 . The function of the impactor is to remove very large droplets from the aerosol. This is to prevent excess liquid from entering the drying tube 1005 is introduced for which complete evaporation cannot be achieved because the transport flow in the drying tube 1005 is saturated. Furthermore, it can serve to at least reduce the overall size distribution of the droplets contained in the aerosol by eliminating the large droplets.

Although the CAD system 1000 Although it can produce satisfactory results in some cases, it may have certain disadvantages and limitations. In particular, it was found that the 1 CAD system shown 1000 is not ideal. In particular, the results (ie the one with the ammeter 1010 measured current) strongly depend on the solvent used. This means that the same sample in different solvents can produce different currents on the ammeter 1010 result, which can make the further use of the results cumbersome and limit the overall usability.

Put simply, previous CAD systems can have the disadvantage of being highly dependent on the solvent used. For example, the same concentration of a sample can lead to different currents depending on whether the sample was dissolved in water or in methanol.

There are several reasons for reliance on solvents in previous systems, such as: B. the system 1000 from 1 . The amount of liquid that goes into the drying tube 1005 depends on the size of the portion that is separated off by the impactor and thus of course cannot contribute to the measurement. Furthermore, the physical properties of the liquid in pneumatic atomization lead to droplets of different sizes. This means that different liquids lead to a significantly different size distribution of the droplets generated. A certain amount of liquid, distributed over a few large droplets, leads to a certain measuring current. However, if the same amount of liquid is distributed over many small droplets, the measuring current is significantly higher. For the correct interpretation of the measurement results, it can therefore be advantageous to know the amount of liquid and, in particular, the size distribution of the droplets or particles.

With reference to 2 Embodiments of the present invention can overcome or at least mitigate these shortcomings and disadvantages. It will be understood that the present invention can utilize any of the features described above in connection with the prior art. The CAD system 2000 However, in addition to the components described above, it also includes a measuring unit 100 . the Measuring unit 100 can be designed to provide data for determining at least one parameter of the particles or the droplets, such as e.g. B. a size and / or frequency parameter to provide. The measuring unit is located in the embodiment shown 100 between the spray chamber 2004 and the drying tube 2005 . This measuring unit can thus measure the at least one parameter of the droplets before they enter the drying tube 2005 measure up. In other embodiments of the present invention, however, it is also possible to determine the at least one parameter of the particles contained in the secondary aerosol, ie on one of the drying unit 2005 downstream point. In the in 2 illustrated embodiment, the measuring unit 100 however, determine at least one parameter of the droplets.

The system 2000 may include any of the components typically used in prior art CAD systems, as in 2 shown, or in other embodiments, the measuring unit 100 be integrated into a CAD system that includes only part of the prior art and possibly other components. An example (see 3 ) can be a system that has a droplet generator 2003 which can provide means for directly controlling the droplet size distribution. Thus, in some embodiments, the system may not have a spray chamber 2004 and / or no expiration 2006 requires.

A known droplet size distribution can make it possible to interpret the from the flow measuring unit 2010 to improve the measured signal. That is, by knowing the droplet size distribution (and / or the particle size distribution) means can be provided to obtain a more precise measurement of the analyte amount, since different droplet sizes lead to different particle sizes and thus to different signals for the same total analyte amount. Thus, embodiments of the present invention can overcome the problem of the droplet size and / or the solvent dependency of the measurement results. In general, the means mentioned above can make the interpretation of the measurement result relatively independent of the solvent used.

In some embodiments (not shown) the measuring unit 100 the drying unit 2005 be arranged downstream. That is, the unit of measurement 100 can the drying tube 2005 determine at least one parameter of the particles downstream.

2 shows a CAD system 2000 according to embodiments of the present invention. The CAD system 2000 can also be used as a system 2000 are designated. Simply put, the system includes 2000 a gas inlet 2002 to supply the system 2000 with a gas, for example an inert gas, such as. B. nitrogen, and an effluent inlet 2001 . In some embodiments, the inlet can be an HPLC inlet 2001 for directing an HPLC column effluent. The gas inlet 2002 can also be used as an inert gas inlet 2002 are designated. The HPLC inlet 2001 can also be used as an HPLC column effluent inlet 2001 or simply as a liquid inlet 2001 are designated. Here, too, it goes without saying that it is not crucial that the present technology is used in an HPLC system, ie the sample can also be supplied from a unit other than an HPLC column.

The system 2000 also includes a droplet generator 2003 for creating a spray of fine droplets from a liquid emerging from a liquid inlet 2001 is supplied, the droplets in a gas flow emanating from a gas inlet 2002 is supplied to be carried away. Such a droplet generator unit can, for example, be an atomizer 1003 as known in the art.

In simple terms, a liquid (e.g. an HPLC effluent) becomes a droplet generator 2003 via an effluent inlet 2001 fed. At the same time the droplet generator is 2003 via a gas inlet 2002 fed with a gas. The droplet generator 2003 creates a droplet spray by breaking the liquid into droplets that are ejected into a flow of inert gas. The droplets formed can pass through a spray chamber 2004 that contains an impactor to remove very large droplets from the aerosol (but this may be optional). Excess fluid can lead to a drain 2006 and thus do not contribute to the measurement. This is to prevent excess liquid from getting into the drying unit 2005 is introduced, for example, a drying tube 2005 (also as an evaporation pipe 2005 designated) can be.

Embodiments of the present technology can include a measurement unit 100 include that of the drying unit 2005 is arranged upstream or downstream (not shown). The unit of measurement 100 can determine at least one parameter of the aerosol, such as. B. a size parameter or a frequency parameter of the droplets or particles. A size parameter can be, for example, a mean value for a distribution for the size of the droplets or particles and / or a width of a distribution for the size of the droplets or particles, while a frequency parameter can be, for example, a mean frequency of particles / droplets passing through the measuring unit. Here the measurement concerns droplets, if the measuring unit 100 the drying unit 2005 is arranged upstream, and particles, if they are the drying unit 2005 is arranged downstream. It goes without saying that certain analytes remain in the drying unit even after the solvent has been removed 2005 can be in a liquid phase. For the sake of simplicity, the analyte can after the drying unit 2005 can also be summarized under the term “particle” when it is in a liquid phase.

In the following, the measurements are discussed with reference to droplets. However, those skilled in the art will understand that the same applies to particles when the measuring unit 100 the drying unit 2005 is arranged downstream.

In particular, the measuring method of the measuring unit 100 be non-destructive. That is, the process of measuring the at least one parameter must not change the movement path of the droplets significantly and / or modify the individual droplet sizes. The measurement result (ie that of a current measurement unit 2010 , also as an ammeter 2010 designated, measured current) is therefore not significantly affected. In other words, it is the one with the ammeter 2010 measured current regardless of the use of the measuring unit 100 .

After drying, particles are produced that enter a charger, and especially a mixing chamber 2008 of the charger. The charger charges the particles, for example by diffusion charging, as discussed. That is, in the mixing chamber 2008 the aerosol is combined with an influx of ionized protective gas. In such a configuration the system can 2000 (and especially the charger) also has an ionizer 2007 include, which is designed to ionize the protective gas, ie to charge it electrically. It should be understood that the gas inlet 2002 for the gas supply after the drying unit 2005 the gas inlet 2002 can be that the gas to the droplet generator 2003 feeds. In other embodiments, however, separate gas inlets (which can also be referred to as gas supplies) for the droplet generator can also be used 2003 and the charger 2008 be used. The person skilled in the art understands that the charging process described is only an example and that other means for charging the aerosol particles can be used in the charger. Such methods, for example, may not require a supply of an inert gas and / or an ionizer 2007 .

Before entering the current measuring unit 2010 the charged particles and the excess charged gas can create an ion trap 2009 happen that eliminates the ions of high electrical mobility, ie the ion trap 2009 eliminates charged gas particles as well as small charged particles - typically particles smaller than about 6 nm can be removed by the ion trap. These particles can also be referred to as beta-1 particles. The current measuring unit 2010 can be an ammeter and it can also be used as an ammeter 2010 or simply as an ammeter 2010 are designated.

The ammeter then transmits 2010 a signal to a terminal 2011 . The one from the ammeter 2010 emitted signal is the result of the discharge of the charged particles. The intensity of the signal is proportional to the amount of charge contained in the particles. It will be understood that a higher amount of sample in the liquid in the primary aerosol will generally result in more charge and higher currents. The charge (and the current) is therefore also a measure of the amount of sample, also known as the analyte, in the liquid.

In short, the CAD system works 2000 by making it from a liquid and a gas that a droplet generator 2003 is supplied, a droplet spray, also known as an aerosol, is generated. Large droplets can be in a spray chamber 2004 deposited with an impactor and removed from the aerosol. Then, for example, the droplet size or frequency of the aerosol can be measured by the measuring unit 100 can be determined non-destructively. The droplets are in the drying unit 2005 can be dried to produce particles, and the particles can be passed from a gas flow to a charger, e.g. B. a mixing chamber 2008 a charger. In the charger, the particle is charged with a surface charge, e.g. B. acted upon by an ionized gas and charges with high mobility can pass through an ion trap 2009 be eliminated. Then the charged particles are measured with an ammeter 2010 measured and the measured current is related to the amount of analyte in the injected sample and can be used in the terminal 2011 expressed as a chromatographic spectrum.

It goes without saying that the measuring unit 100 can also determine at least one parameter of the secondary aerosol, ie the particles. In other words, the measuring unit 100 also the drying unit 2005 downstream, for example adjacent to the charger, between the ion trap 2009 and the current measuring unit 2010 , etc. be arranged. In some embodiments, the measurement unit 100 the ion trap 2009 downstream and the current measuring unit 2010 be arranged upstream.

With reference to 3 In some embodiments, the CAD system may include a droplet generator 2003 which can produce an aerosol with a relatively controlled size distribution. Thus, in some embodiments of the present invention, the spray chamber 2004 can be omitted.

Such a droplet generator 2003 can for example generate droplets with a defined droplet generation frequency. That is, the droplet generator 2003 can apply a frequency to avoid disturbances in a liquid jet, e.g. B. effluents, which lead to the fact that the jet is broken up into droplets. The frequency used can be adjusted according to the flow of liquid from the droplet generator 2003 is supplied, be set so that the disturbances caused at least approximately coincide with the fastest growing natural disturbance in the liquid jet. In this way, the droplets formed can predominantly have a diameter which is directly related to the diameter of the outlet opening, ie where the liquid jet enters the pipeline of the droplet generator 2003 leaves. Such frequency-controlled droplet formation can lead to a relatively narrow droplet size distribution that is independent of the constituents of the effluent, e.g. B. the solvents used is. Further details can be found in the German patent application filed by Dionex Softron GmbH on November 11, 2018 DE 10 2018 129 812.9 which is incorporated herein by reference in its entirety.

The system can also 2000 a flow control unit that controls the flow to the droplet generator 2003 can control. That is, the flow unit can supply a relatively constant flow of liquid to the droplet generator, e.g. B. provide effluents independent of the fluctuations in the liquid flow at the inlet of the flow control unit. Again, further details of the flow control unit are in the German patent application filed on November 11, 2018 DE 10 2018 129 812.9 of Dionex Softron GmbH, which is incorporated herein by reference in its entirety.

In particular, a combination of a flow control unit and a frequency-controlled droplet generator can be advantageous, since it enables a very stable generation of a relatively constant and narrow droplet size distribution independent of flow fluctuations and effluent components.

Now is on 4th Reference is made to an exemplary of the drying unit 2005 upstream (and the droplet generator 2003 downstream) measuring unit 100 represents. The unit of measurement 100 can be an imaging device 102 which is intended to take pictures of the aerosol, e.g. B. a camera system or simply an image sensor. The imaging device 102 can be arranged in a plane parallel to the direction of flow of the aerosol. That is, the imaging device 102 may be oriented to provide means for capturing images of the aerosol with droplets passing through the frame of the imaging device from left to right and far enough away so as not to interfere with the droplet spray. The term “recording of images” can refer to a process of generating image data in accordance with an image captured by the image sensor.

The camera axis, ie the axis perpendicular to the image sensor of the imaging device 102 , or in other words the viewing direction of the imaging device, can form an angle with the flow direction of the aerosol. The angle can range from 45 ° to 135 °, preferably 75 ° to 105 °, such as. B. 85 ° to 95 °.

The imaging device can also include optical elements, such as e.g. B. lenses, include to improve the imaging ability of the image sensor. For example, lenses can provide means to adjust the focus in the correct plane and / or to increase the light reaching the image sensor.

Furthermore, the measuring unit 100 a light source 101 include. The light source 101 can either be a continuous light source, such as B. LEDs or a gas discharge lamp, or a pulsed light source such. B. a stroboscope. That is, in some embodiments the light source can provide precisely defined light pulses and in other embodiments it can provide light continuously. In some embodiments, the light source can also be a coherent laser light source, such as a laser light source. B. a continuous wave (CW) - or a pulsed laser.

The light source can be arranged to provide illumination for the imaging device 102 but does not affect the aerosol. For example, the light source 101 in the same direction as the imaging device 102 (not shown) facing or facing the imaging device 102 be placed.

In the in 4th The embodiment shown is the measuring unit 100 the drying unit 2005 arranged downstream. In this case it measures the unit of measurement 100 the droplets, ie it provides data for determining at least one parameter of the droplets, e.g. B. Size parameters (e.g., an average size and a standard deviation). As discussed, however, this is only an example. As discussed, it is understood that the measuring unit 100 can also be arranged downstream of the charger, for. B. the ion trap 2009 downstream and the current measuring unit 2010 upstream. In this case, the measuring unit would provide data in order to determine at least one parameter of the particles, e.g. B. Size parameters.

In the in 4th The embodiment shown is the measuring unit 100 as a size measurement unit 100 implemented so that size parameters can be determined in this embodiment. It should be understood, however, that this is only exemplary. As a further example, the measuring unit 100 can also be implemented as a frequency measuring unit for measuring a frequency of droplets or particles. In this case the measuring unit can 100 can be implemented as a light barrier.

The Charged Aerosol Detector System 2000 can also include a processing unit 2012 which is designed to be used by the measuring unit 100 and / or the current measuring unit 2010 to receive and analyze the provided data. The processing unit 2012 can use the at least one parameter from the measurement unit 100 Determine delivered data and determine an analyte flow rate based on the measured current and a subset of the at least one parameter. The subset can include at least one parameter and it is understood that a subset can also include all of the processing unit 2012 may include certain parameters. In other words, a subset of a sentence may include the entire sentence.

The processing unit 2012 can furthermore be designed to transmit the parameters (or a selection thereof), the measured current and / or the determined analyte flow to the terminal device 2011 to send. The terminal can be designed to convert at least part of the received data into a human-readable signal. The human readable signal can include a chromatographic spectrum.

The processing unit 2012 can at least one microprocessor, such as. B. a central processing unit (CPU) and / or at least one circuit such. B. an application specific integrated circuit (ASIC), field programmable gate arrays (FPGAs), etc. include.

Furthermore, the CAD system 2000 at least one memory, such as. B. comprise at least one non-volatile storage device (e.g. a solid-state drive (SSD)) and / or at least one volatile storage device (e.g. random access memory (RAM)). Machine-readable program code can be stored in memory. When executed on the processor or the circuit, the machine-readable code can be designed for the processing unit 2012 to cause the tasks and steps to be carried out which are necessary for the extraction of at least one parameter of an aerosol.

Furthermore, the measuring unit 100 a control unit 103 that is configured to enable the synchronous operation of the imaging device 102 and the light source 101 ensure, especially in cases where the light source 101 is a pulsed light source. The pulsation of the light source 101 synchronous with the imaging device 102 can change the resolution and performance of the measuring unit 100 optimize.

In some embodiments of the present invention, the measuring unit can 100 use the direct imaging of the aerosol to determine the at least one parameter. That is, the imaging device 102 can take digital photos of the aerosol. These photos are then used by the processing unit 2012 processed and analyzed to determine the at least one parameter. The imaging system can thus be, for example, a high-speed camera. It goes without saying that images or photos can be used interchangeably, and an image can be represented by image data, that is, a processing unit 2012 that analyzes an image can refer to the processing unit 2012 which analyzes the image data.

In further embodiments of the present invention, the measuring unit 100 based on a method of light diffraction, in particular laser diffraction. Thus, the light source can 101 be a coherent laser light source directly opposite the imaging device 102 is located. The laser beam from the light source can pass through the aerosol spray before leaving the imaging device 102 is captured.

Smaller particles scatter the light at larger angles with respect to the laser beam compared to larger particles that scatter at smaller angles. Thus, this includes as angular intensity on the imaging device 102 recorded angular diffraction patterns information on particle sizes. Therefore, this can be done by the imaging device 102 then recorded patterns by the processing unit 2012 be analyzed, in particular to identify at least one size parameter of the particles or droplets. The pattern can can be described using the Mie theory. However, this method can also lead to a frequency parameter.

The laser light source can be used to optimize resolution and performance 101 synchronous with the imaging device 102 be pulsed.

The processing unit 2012 can machine learning such as Example, use pattern recognition algorithms to improve the accuracy of the analysis of the imaging device data.

It should be noted that while the system is primarily designed to determine a magnitude or frequency parameter, it can also be used to extract other parameters, e.g. B. velocity or momentum components of the droplets or particles, which can further improve the accuracy of the measurements.

The following is the unit of measurement 100 mainly as the drying unit 2005 upstream described. The unit of measurement 100 however, it can alternatively be placed at any point near the droplet generator 2003 downstream and the current measuring unit 2010 , ie the ammeter 2010 , is upstream. In other words, the measuring unit can, for example, be the drying unit 2005 directly upstream (as in 4th shown), right next to the charger (which is the mixer changer 2008 inside the charger, between the ion trap 2009 and the ammeter 2010 etc. can be placed.

With reference to 5 can the measuring unit 100 in some embodiments of the present invention, a light barrier 110 include, which is designed to detect any object that the light path of the light barrier 110 blocked.

In general, a light barrier can be a light source 101 , also as a light transmitter 101 and a light sensor 105 , also as a photoelectric receiver 105 or just recipient 105 referred to include. The light can come from the light source 101 to the light sensor 105 as indicated by the arrow. Whenever an object is the light path (arrow) between the light source 101 and the light sensor 105 blocked, the light barrier registers 110 the absence (or at least the reduction) of light hitting the light sensor 105 achieved.

In some embodiments, the light source can 101 and the light sensor 105 facing each other, as in the left field of 5 shown. That is, the light barrier 110 can be a one-way light barrier. Whenever there is a droplet or particle between the light source 101 and the light sensor 105 the light sensor registers 105 the reduction or absence of light reaching the sensor 105 achieved because the droplet or particle is blocking the light path.

In further embodiments, the light source 101 and the light sensor 105 aligned in the same direction next to each other and the light can come from a reflector 106 be reflected, as in the right field of 5 shown. This means that the light barrier can be a reflection light barrier. Preferably the light sources are 101 and the light sensor 105 placed directly next to each other in order to minimize the total path length of the light (indicated by the arrows) and / or the angle of reflection. Similar to before, due to the reduction or absence of light reaching the light sensor, any droplets or particles that pass the light path can be registered. The reflector 106 can generally be a surface suitable for the wavelength of the light source 101 emitted light is highly reflective, e.g. B. a mirror with a corresponding coating.

For the one-way light barrier, the one from the light source happens 101 light beam emitted the volume of interest only once, ie the area in which the droplets or particles can be detected, which is preferable to the reflection light barrier, which can be slightly less accurate due to the longer light beam and the angle of reflection.

The light source 101 and / or the light sensor 105 may include optical elements designed to modify the propagation of light. For example, the light source can comprise a lens in order to focus the light by refraction in order to achieve precisely defined light rays. Analogously, the light sensor can comprise a lens in order to direct the incident light onto the sensor section of the light sensor 105 to focus. Furthermore, the light sensor 101 and / or the light sensor 105 be equipped with optical fibers, for example if the special requirements of the light source 101 and the light sensor 105 for the desired position of the light barrier 110 are too high.

Typically the light source can 101 for example an LED or a laser diode. In some embodiments, the light source can 101 be modulated. This can be beneficial if there are other light sources nearby, as this will affect the light sensor 105 can enable that from the intended light source 101 to distinguish emitted light from other light sources.

The light sensor 105 can be an optoelectronic sensor such. B. a photodiode Photo resistor or a photo transistor. That is, the light sensor 105 can be designed to convert light into an electrical signal using the photoelectric effect.

In general, the photocell can 110 detect the presence of a particle or droplet in the light beam and thus for an aerosol that passes through the light beam of the light barrier 110 flows, generate frequency data. That is, it can generate data about the frequency of a particle or droplet that crosses the light barrier 110 happened.

The frequency data can make it possible to determine the mean value for the size of the particles or droplets. For measurements of droplets, the average volume of a droplet can be derived taking into account the total effluent flow to the droplet generator. Those skilled in the art will understand that the droplets of the drying unit 2005 measured upstream.

$\raisebox{1ex}{$N$}\!\left/ \!\raisebox{-1ex}{$t$}\right..$

Die Gesamtzahl N kann in Form des Gesamtvolumens V_t und des durchschnittlichen Tröpfchenvolumens V̅ ausgedrückt werden.The light barrier 110 can provide an average droplet frequency v̅ _d , which can be approximated as the total number of droplets N over the time t: ${\overline{v}}_d=\raisebox{1ex}{$N$}\!\left/ \!\raisebox{-1ex}{$t$}\right..$

$\raisebox{1ex}{$N$}\!\left/ \!\raisebox{-1ex}{$t$}\right..$

The total number N can be expressed in terms of the total volume V _t and the average droplet volume V̅.

wobei F_t den gesamten Effluentenfluss angibt, der dem Tröpfchengenerator 2003 zugeführt wird. Somit kann das mittlere Tröpfchenvolumen näherungsweise angegeben werden als $$\overline{V}=\frac{F_t}{{\overline{v}}_d}.$$

Therefore, the average droplet frequency can be approximated as $${\overline{v}}_d=\frac{N}{t}=\frac{V_t}{\overline{V\ast t}}=\frac{{\mathrm{F.}}_t}{\overline{V}},$$

where F _{t is} the total effluent flow that the droplet generator 2003 is fed. Thus, the mean droplet volume can be approximated as $$\overline{V}=\frac{{\mathrm{F.}}_t}{{\overline{v}}_d}.$$

Similar considerations apply when using the measurement unit 100 as a light barrier 110 is carried out that of the ion trap 2009 downstream and the current measuring unit 2010 is arranged upstream. By using such a light barrier 110 a frequency of particles can be determined, which is in the direction of the current measuring unit 2010 to fly. This particle frequency can be measured together with the current on the current measuring unit 2010 can be used to determine the average current passed by a particle to the current measuring unit 2010 is carried, which depends on the particle size and thus on the amount of analyte.

With reference to the 6A until C. the relationship between the measured current, the analyte flow and the particle size is illustrated. As stated previously, a fixed amount of analyte that is distributed over a few large particles results in a significantly different current than the same amount of analyte that is distributed over many small particles. The change can be estimated based on a few assumptions, as shown below.

The loading process in the mixing chamber 2008 can be referred to as diffusion charging. Therefore the charge of a particle q _p on the collector can be specified as approximately proportional to the diameter d _{p of} the particle: q _p ∝ d _p .

For an aerosol, ie a particle spray mist, the particles can have a specific size distribution. For the sake of simplicity, it is assumed that all particles have the same size, ie all particles have the average particle size with an average particle diameter d̅ _p . Thus, the mean charge per particle can be given as approximately proportional to the mean diameter of the particle size distribution: q̅ _p ∝ d̅ _p .

zugeordnet werden und somit kann eine Gesamtzahl von Partikeln $N=\raisebox{1ex}{$V$}\!\left/ \!\raisebox{-1ex}{$\overline{V}$}\right.$

betragen, wobei V das Gesamtanalytvolumen angibt.In addition, each particle in the aerosol can have an average volume $\overline{V}\propto {\overline{d}}_p^3$

can be assigned and thus a total number of particles $N=\raisebox{1ex}{$V$}\!\left/ \!\raisebox{-1ex}{$\overline{V}$}\right.$

where V indicates the total analyte volume.

und der entsprechende Strom als $$I\propto \frac{V}{t}\ast {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}=F_a\ast {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.},$$

wobei F_a den Analytfluss angibt.Therefore, the total charge can be approximated as $$Q\propto N\ast {\overline{d}}_p\propto V\ast {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.},$$

and the corresponding stream as $$\mathrm{I.}\propto \frac{V}{t}\ast {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}={\mathrm{F.}}_a\ast {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.},$$

where F _a indicates the analyte flow.

wobei V̅ das durchschnittliche Partikelvolumen ist.Thus the current for a given particle size distribution depends linearly on the analyte flow. For a given flux, the current is proportional to ${\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.},$

where V̅ is the average particle volume.

Therefore, the analyte flow F _a can be determined based on the average particle volume, ie a size parameter, and the measured current.

Further assuming that the particle size is proportional to the droplet size, the analyte flow F _{a can} also be determined based on a size parameter extracted from a measurement of the droplets and a total liquid flow (ie, a flow of the liquid from which the droplets are formed) became. It goes without saying that the assumption that the particle sizes are proportional to the respective droplet sizes can generally be useful for a given point in time t and for a known total liquid flow.

At any point in time t, the liquid flow from which droplets are formed has a concentration of the analyte in the solvent. If droplets are formed from this liquid at time t, these droplets generally also have this analyte concentration (this assumption applies at least to all cases in which there is a large number of analyte molecules in each droplet). Thus, when the droplets are formed, the amount of analyte in a droplet is proportional to the concentration and volume V _{droplets of} the droplet, ie $$\mathrm{A.}naly{t}_{TröpfcHen}\propto KOnzentratiOn\cdot V_{TröpfcHen}.$$

It goes without saying that the concentration for a given analysis flow depends on the total liquid flow (for a given analysis flow: the higher the total liquid flow, the lower the concentration). Thus, for the present considerations, the total liquid flow is also regulated and / or determined.

After a particle has been generated from this droplet, the amount of analyte in this particle corresponds to the amount of analyte present in the droplet, ie $$\mathrm{A.}naly{t}_{\mathrm{P.}artikel}=\mathrm{A.}naly{t}_{TröpfcHen}.$$

Furthermore, the volume V of the particle after drying is proportional to the amount of analyte in the particle, ie $$V_{\mathrm{P.}artikel}\propto \mathrm{A.}naly{t}_{\mathrm{P.}artikel}.$$

The combination of these equations leads to $$V_{\mathrm{P.}artikel}\propto V_{TröpfcHen}.$$

In this way, the size of the droplets can also be observed. Here, too, the use of the measured current and the size parameter can enable a better determination of the amount of analyte.

In addition, the average particle volume V̅ can also be estimated based on these assumptions, taking into account the measured current I and the average particle frequency v̅ _p . $$\mathrm{I.}\propto \frac{N}{t}\ast {\overline{d}}_p\propto {\overline{v}}_p\ast {\overline{d}}_p\propto {\overline{v}}_p\ast {\left(\overline{V}\right)}^{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}.$$

Thus, the average particle volume can be approximated as $$\overline{V}\propto \raisebox{1ex}{${\mathrm{I.}}^3$}\!\left/ \!\raisebox{-1ex}{${\overline{v}}_p^3$}\right..$$

analog zur obigen Betrachtung angegeben werden (wobei F_a der Analysefluss und v̅_p die durchschnittliche Partikelfrequenz ist). Somit kann der Strom ferner näherungsweise angegeben werden als $$I\propto {\overline{v}}_p\ast {\left(\overline{V}\right)}^{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}\propto {\overline{v}}_p{}^{\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}\ast F_a{}^{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}$$

und folglich kann der Analytfluss näherungsweise angegeben werden als $$F_a\propto I^3\ast {\overline{v}}_p{}^{-2}.$$

Alternatively, the analyte flow can also be estimated directly based on the average particle frequency. The average volume of a particle can also be approximated as $\overline{V}\propto \frac{{\mathrm{F.}}_a}{{\overline{v}}_p}$

analogous to the above consideration (where F _{a is} the analysis flow and v̅ _{p is} the average particle frequency). Thus, the current can also be specified approximately as $$\mathrm{I.}\propto {\overline{v}}_p\ast {\left(\overline{V}\right)}^{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}\propto {\overline{\mathrm{<figure-callout\; id="2"\; label="v\; ̄\; p"\; filenames="DE102019125170B4\_0024.png"\; state="\{\{state\}\}">v</figure-callout>}}}_p{}^{\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}\ast {\mathrm{F.}}_a{}^{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}$$

and hence the analyte flow can be approximated as $${\mathrm{F.}}_a\propto {\mathrm{I.}}^3\ast {\overline{v}}_p{}^{-2}.$$

The average particle volume and / or the analyte flow can therefore be derived from a frequency parameter and / or a size parameter.

The above-discussed dependency of the measured current, the analyte flow and the particle size is also in the 6A until C. shown as an example. 6A shows an exemplary graph of the current I versus the average particle volume V̅ and the flow F _a (all in arbitrary units) and 6B and 6C represent sections of this graph along the flow F _a ( 6B) and along the average particle size V̅.

As in 6B shown, in the theoretical case that the other parameters (and in particular the average particle size) are kept constant, there is a proportional relationship between the analyte flow F _a and the current. That is, if the analyte flow rate doubles, the current also doubles if everything else is kept constant. However, the dependence on the particle size, i.e. the volume, is non-linear (cf. 6C ). In other words, if we assume a constant analyte flow, but double the average particle size, the measured current is about 37% lower, although the analyte flow is the same. A change in the particle size can therefore lead to significantly different measurement results for the analyte amount, although the analyte amount is kept constant.

In view of this, it can be very advantageous to determine at least one size or a frequency parameter of the droplets or particles, since this can make it possible to correct the measured current signal and thus to extract the analyte flow rate with greater accuracy. This can be achieved by embodiments of the present invention.

zwischen dem durchschnittlichen Partikelvolumen V̅ und dem Strom I.The overall dependence of the current I on the analyte flow F _a and the average droplet volume V̅ is in 6A shown. Here, too, there is again a linear relationship between the analyte flow F _a and the current and a relationship $\mathrm{I.}\propto {\left(\overline{V}\right)}^{-\raisebox{1ex}{$2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}$

between the average particle volume V̅ and the current I.

It is therefore understood that for a given current I there can be different combinations of particle sizes V̅ and analyte flow F _a which would lead to this current. In relation to 6A these combinations are located on a contour line (which can also be referred to as an isoline). Thus, the measured flow alone (without information about the droplet size distribution) may not make it possible to provide the flow.

In embodiments of the present invention, however, at least one size or frequency parameter is also specified which indicates a size of the droplets or of the particles, for example the average particle volume. With this information, a measured current I can be assigned to _{an analyte flow F a.} Thus, embodiments of the present invention improve the accuracy of a charged aerosol detector.

While the above has described the logic (for the sake of simplicity) assuming that all particles are the same size, it should be understood that the concept described can be achieved by determining the size distribution (e.g. the average particle size and a standard deviation ) can also be applied to other situations.

Since different solvents can produce droplets with different size distributions, embodiments of the present invention can also help to eliminate the solvent dependency, since the droplets with different sizes are taken into account by the present invention.

That is, embodiments of the present invention generally relate to detectors for charged aerosols in which, in addition to the current, a parameter is also determined which indicates the particle sizes. The determination of both the current and the particle sizes can make it possible to determine the analyte flow with great accuracy.

Whenever a relative term such as “approximately,” “substantially,” or “approximately” is used in this specification, that term should also be construed to include the exact term. That means z. B. that “essentially straight” should be interpreted to include “(exactly) straight”.

Whenever steps are mentioned in the preceding statements and also in the appended claims, it should be pointed out that the order in which the steps are mentioned in this text can be irrelevant. This means, unless stated otherwise or unless this is clear to the person skilled in the art, that the order in which the steps are named can be of secondary importance. That means, if the present document z. B. determines that a method comprises steps (A) and (B), this does not necessarily mean that step (A) takes place before step (B), but it is also possible that step (A) (at least partially ) takes place simultaneously with step (B) or that step (B) takes place before step (A). If it is also stated that a step (X) takes place before a further step (Z), this does not imply that no further step takes place between steps (X) and (Z). This means that the fact that step (X) takes place before step (Z) includes the situation that step (X) takes place immediately before step (Z), but also the situation that (X) takes place before one or more of the Steps (Y1), ... followed by step (Z), takes place. Corresponding considerations apply when terms such as “after” or “before” are used.

While a preferred embodiment has been described in the foregoing with reference to the accompanying drawings, those skilled in the art will understand that this embodiment has been provided for the purpose of illustration only and is in no way to be construed as limiting the scope of this invention, which is defined by the claims should.

Claims (10)

Charged Aerosol Detector System (2000), the system comprising: a droplet generator (2003) designed to generate droplets, a drying unit (2005), which is designed to dry the droplets and thus generate particles, a charger designed to charge the particles, a current measuring unit (2010) configured to measure a current generated by the charged particles, and a measuring unit (100) which is designed to provide data for determining at least one parameter of the particles or the droplets, the measuring unit (100) being upstream of the flow measuring unit (2010), wherein the at least one parameter at least one size parameter for a size of the particles or the droplets; and or comprises at least one frequency parameter for a frequency of the particles or the droplets. The system according to the preceding claim, wherein the system comprises a processing unit (2012) which is configured to receive and analyze the data from the measuring unit (100) in order to determine the at least one parameter. The system of the preceding claim, wherein the processing unit (2012) is configured to determine an analyte flow rate based on the measured current and a subset of the at least one parameter. The system of the preceding claim, wherein the system further comprises a terminal (2011), wherein the processing unit (2012) is designed to send the parameters, the measured current and / or the analyte flow rate to the terminal (2011); and wherein the terminal (2011) is designed to convert at least part of the received data into a human-readable signal. The system of any preceding claim, wherein the measurement unit (100) is further a light source (101); and an imaging device (102) and / or a light sensor (105). System according to the preceding claim, wherein the measuring unit comprises a light barrier (110), which comprises the light source (101) and the light sensor (105), wherein the light barrier (110) is designed to provide data about particles or droplets that the light barrier (110) happen. A method for determining an amount of an analyte flow, the method comprising the use of a system according to any one of Claims 1 until 6th wherein the method comprises: providing a flow of a liquid comprising the analyte, creating droplets of the liquid, drying the droplets and thus creating particles, charging the particles, measuring a current generated by the charged particles, and determining at least one Parameters of particles or droplets; wherein determining the at least one parameter comprises at least one of the following points: determining at least one size parameter for a size of the particles or the droplets; and determining at least one frequency parameter for a frequency of the particles or the droplets. Method according to the preceding claim, wherein the method comprises one of the following points: Observing the particles and determining the at least one parameter based on this observation; and Observing the droplets and determining the at least one parameter based on this observation. A method according to the preceding claim, wherein the system comprises the features of Claim 2 wherein the method further comprises that the processing unit receives and analyzes data from the measuring unit (100) and the processing unit (2012) determines the at least one parameter. The method of the preceding claim, wherein the method comprises the processing unit (2012) determining the analyte flow rate based on the measured current and a subset of the at least one parameter.

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