阅读说明：本技术 测定气溶胶递送的装置和方法 (Device and method for determining aerosol delivery ) 是由 F·维甘特 G·波尔曼 于 2019-07-02 设计创作，主要内容包括：本发明涉及一种用于测定气溶胶流(112)的气溶胶递送(210)的装置(110)和方法,和一种测定气溶胶颗粒(220)上的液体的吸收和/或吸附的方法。装置(110)包含：收集单元(116),所述收集单元(116)具有设定用于收集由气溶胶流(112)携带的气溶胶颗粒(120)的过滤器(118),可连接至气溶胶产生器(114)的第一流体连接点(122),和可连接至设定用于模拟潮式呼吸的呼吸模拟器(126)的第二流体连接点(124)；至少一个测量体积(130),其设计用于使至少一个光束与由气溶胶流(112)携带并穿过所述测量体积(130)的气溶胶颗粒(120)相互作用；至少一个光学测量单元(136),其设计用于根据所述至少一个光束与所述穿过测量体积(130)的气溶胶颗粒(120)的相互作用来产生至少一个光学测量信号；和至少一个评估单元(140),其设计用于从所述至少一个光学测量信号测定气溶胶流(112)的气溶胶递送(210)。(The invention relates to a device (110) and a method for determining aerosol delivery (210) of an aerosol flow (112), and a method of determining absorption and/or adsorption of a liquid on aerosol particles (220). The apparatus (110) comprises: a collection unit (116), the collection unit (116) having a filter (118) configured for collecting aerosol particles (120) carried by an aerosol flow (112), a first fluid connection point (122) connectable to an aerosol generator (114), and a second fluid connection point (124) connectable to a breathing simulator (126) configured for simulating tidal breathing; at least one measurement volume (130) designed for interacting at least one light beam with aerosol particles (120) carried by an aerosol flow (112) and passing through the measurement volume (130); at least one optical measurement unit (136) designed for generating at least one optical measurement signal as a function of an interaction of the at least one light beam with the aerosol particles (120) passing through the measurement volume (130); and at least one evaluation unit (140) which is designed to determine an aerosol delivery (210) of the aerosol flow (112) from the at least one optical measurement signal.)

1. A device (110) for determining aerosol delivery (210) of an aerosol stream (112) generated by an aerosol generator (114), the device (110) comprising:

-a collection unit (116), the collection unit (116) having a filter (118) configured for collecting aerosol particles (120) carried by an aerosol flow (112), a first fluid connection point (122) connectable to an aerosol generator (114), and a second fluid connection point (124) connectable to a breathing simulator (126) configured for simulating tidal breathing;

-at least one measurement volume (130) designed for interacting at least one light beam with aerosol particles (120) carried by an aerosol flow (112) and passing through the measurement volume (130);

-at least one optical measurement unit (136) designed for generating at least one optical measurement signal depending on an interaction of the at least one light beam with the aerosol particles (120) passing through the measurement volume (130); and

-at least one evaluation unit (140) designed for determining an aerosol delivery (210) of the aerosol flow (112) from the at least one optical measurement signal.

2. The device (110) according to the preceding claim, wherein the optical measurement unit (136) is designed for generating the optical measurement signal depending on at least one of an extinction or a scattering of the light beam in the measurement volume (130) when aerosol particles (120) pass through.

3. The device (110) according to any one of the preceding claims, wherein the optical measurement unit (136) is a laser measurement system (138) or comprises a laser measurement system (138), wherein the laser measurement unit (138) is further designed for providing the at least one light beam.

4. The apparatus (110) according to any one of the preceding claims, wherein the light beam is adapted to illuminate a slice within the measurement volume (130).

5. The device (110) according to any one of the preceding claims, wherein the measurement volume (130) is separated from the optical measurement unit (136) by at least one optical window (178), wherein the optical window (178) is set for a light beam to pass through by at least one light beam when entering or leaving the measurement volume (130), wherein the optical window (178) comprises an optically at least partially transparent material.

6. The device (110) according to any one of the preceding claims, wherein the optically at least partially transparent material is homogeneous and free of embedded particles.

7. The device (110) according to any one of the preceding claims, wherein the optical window (178) is arranged in such a way that the light beam passes perpendicularly through the optical window (178).

8. The device (110) according to any one of the preceding claims, further comprising a heating unit configured to heat the at least one optical window (178).

9. The device (110) according to any one of the preceding claims, wherein the measurement volume (130) comprises an inner surface that is smooth and free of edges, recesses and protrusions.

10. The device (110) according to any of the preceding claims, wherein the first fluid connection point (122) is located in front of the filter (118) with respect to the direction of the aerosol flow (112), and wherein the measurement volume (130) is located between the first fluid connection point (122) and the filter (118).

11. A device (110) according to any of the preceding claims, wherein the collecting unit has at least one third fluid connection point (146) to which an air flow unit for generating an air flow (148) is connected, wherein the third fluid connection point (146) is arranged to direct the aerosol flow (112) at least partly by the air flow (148) to the filter (118).

12. The device (110) according to any one of the preceding claims, the device (110) comprising two separate measurement volumes (130), wherein the at least one first optical measurement unit (136) is designed for generating at least one first optical measurement signal depending on an interaction of at least one first light beam with aerosol particles (120) passing through the first measurement volume (130) during an inhalation phase, wherein the evaluation unit (140) is designed for determining a first aerosol delivery (210) of the aerosol flow (112) during an inhalation phase from the first optical measurement signal, wherein the at least one second optical measurement unit (136') is further designed for generating at least one second optical measurement signal depending on an interaction of at least one second light beam with aerosol particles (120) passing through the second measurement volume (130') during an exhalation phase, wherein the evaluation unit (140) is designed for determining a second aerosol delivery (210) of the aerosol flow (112) in the expiration phase from the second optical measurement signal.

13. A method (200) of determining aerosol delivery (210) of an aerosol flow (112), the method (200) comprising the steps of:

a) providing an aerosol stream (112) generated by an aerosol generator (114);

b) directing aerosol particles (120) carried by an aerosol flow (112) through at least one measurement volume (130) and providing interaction of the aerosol particles (120) with at least one light beam within the measurement volume (130);

c) generating at least one optical measurement signal from the interaction of the at least one light beam with aerosol particles (120) passing through the measurement volume (130); and

d) determining an aerosol delivery (210) of the aerosol flow (112) from the at least one optical measurement signal, wherein a transfer function between the optical measurement signal and the aerosol delivery (210) is used.

14. The method (200) according to any one of the preceding claims, wherein the transfer function is determined by performing the following step e) at least once:

e) collecting aerosol particles (120) carried by an aerosol flow (112) in a filter (118), measuring particle loading on the filter (118); the transfer function is determined from the relationship between the particle loading and the at least one optical measurement signal.

15. A method of determining the absorption and/or adsorption of a liquid (220) on aerosol particles (120), the method comprising steps a) to e) according to the preceding method claim and the following step f):

f) at least two optical measurement signals are generated for at least two different particle loadings of the aerosol particles (120), the at least two different particle loadings of the aerosol particles (120) are measured on at least two different filters (118), and the absorption and/or adsorption of the liquid on the aerosol particles (120) is determined from the assumed zero optical measurement signal.

Technical Field

The present invention relates to a device and a method for determining aerosol delivery of an aerosol flow, in particular a dry aerosol flow or a wet aerosol flow comprising absorbed liquid and/or absorbed liquid, and a method for determining absorption and/or adsorption of liquid on aerosol particles.

Background

Pulmonary or respiratory diseases, including but not limited to asthma or Chronic Obstructive Pulmonary Disease (COPD), are typically treated by inhalation of drugs provided as liquid or solid particles in an aerosol flow. Here, the particles generated by using the aerosol generator preferably show a size respirable by alveoli and lungs. In this regard, devices and methods for determining aerosol delivery of an aerosol flow, particularly a dry aerosol flow or a wet aerosol flow containing absorbed liquid and/or absorbed liquid, provided by an aerosol generator are used to develop relevant test parameters.

DIN EN 13544-1: 2007+ A1: 2009 describes a method and device for determining aerosol delivery of an aerosol flow provided by an aerosol generator. The device comprises a collecting unit with a filter for collecting aerosol particles provided by the aerosol flow. The collecting unit has a first fluid connection point located in front of the filter with respect to the direction of aerosol flow and connected to the aerosol generator, and a second fluid connection point located behind the filter with respect to the direction of aerosol flow and connected to a breathing simulator for simulating tidal breathing characterized by successive inhalations and exhalations.

For determining the aerosol delivery of an aerosol flow, in particular a dry aerosol flow or a wet aerosol flow, provided by an aerosol generator, the aerosol generator is connected to a breath simulation unit, in particular to a sinusoidal pump for simulating a breath flow. The filter is placed between the aerosol generator and the breathing simulation unit. The aerosol generator is filled with a quantity of an aerosolizable substance, in particular a1 molar aqueous solution of sodium fluoride (NaF), and operated until aerosol generation is complete. Hereinafter, quantitative chemical analysis was performed.

The filter is selected in such a way that it is capable of retaining at least 95% of the aerosol. For this purpose, high-performance filters of polypropylene can be used in particular. However, the dead volume between the distal end of the patient interface and the corresponding surface of the filter should be limited to 10% or less of the respiratory stroke or tidal volume, which corresponds to a volume of about 0.5 liters for an adult or less than 5 milliliters for a premature infant. To meet this requirement, flat filters are generally used.

However, flat filters are typically low in capacity. This feature severely limits the applicability of planar filters to a large number of aerosols, as frequent filter changes can result in a large number of individual filters requiring quantitative chemical analysis. As a result, the transfer of the measurement results is delayed. In addition, the use of wet aerosols also requires complicated conditioning of the filters in the gravimetric determination of the aerosol samples, which additionally delays the transmission of the measurement results.

DE 102013103152B3 discloses a method and a device for determining the aerosol delivery of an aerosol flow provided by an aerosol generator. The device comprises a collecting unit with a filter for collecting aerosol particles provided by the aerosol flow. Except as already described in DIN EN 13544-1: 2007+ A1: 2009, the collecting unit has, in addition to the first fluid connection point to the aerosol generator and the second fluid connection point to the breathing simulator, at least one third fluid connection point to an air flow unit for generating an air flow. The third fluid connection point is arranged in such a way that: the aerosol flow is at least partially directed by the air flow to the filter.

Here, a closed ventilation circuit is established between the aerosol generator and the sinusoidal pump. Thus, the aerosol flow is directed in a loop from the distal end of the patient interface to the corresponding surface of the filter. Thus, aerosol particles only exit the proximal end of the patient interface if the sinusoidal pump applies an inhalation stroke. In this case, particles are extracted from the patient interface and deposited on the filter. As a result, only the volume between the distal and proximal ends of the patient interface may be considered dead volume. Thus, the method and apparatus for determining aerosol delivery is also applicable to small tidal volumes, which are typical in particular for infants, toddlers, neonates, and premature infants.

WO 2017/133045 a1 discloses an aerosol real-time monitor comprising a laser source assembly for emitting a laser beam and forming a line-shaped laser spot at a particle excitation position of an air stream to be measured; the laser light source assembly is arranged at a laser inlet at the rear end of the closed photoelectric measuring chamber; in a closed photoelectric measuring chamber, the air flow to be measured and the optical axis of a laser beam emitted by a laser light source component intersect at the particle excitation position where a linear laser spot is located in the traveling direction; the scattered light signal reflector and the fluorescence signal reflector are symmetrically arranged on two sides, so that a measuring point formed by intersection of a laser beam emitted by the laser light source component and the air flow to be measured is centered; a scattered light signal detector and a fluorescence signal detector for detecting the scattered light signal and the fluorescence signal passing through the opening of the mirror. The portable monitor is capable of online monitoring.

US 2005/073683 a1 discloses a method and apparatus for identifying individual aerosol particles in real time. The sample aerosol particles are targeted, tracked, and screened to determine which particles qualify for mass spectrometry based on predetermined qualification or selection criteria. Screening techniques include measuring one or more of particle size, shape, symmetry, and fluorescence. Only the qualifying particles that meet all of the screening criteria are subjected to desorption and/or ionization and single particle mass spectrometry to generate a corresponding test spectrum that is used to determine the identity of each qualifying aerosol particle by comparing the test spectrum to a predetermined spectrum of known particle types. However, the use of this method and apparatus results in modification of the particles by ionization of the particles.

US 8,711,338B 2 discloses a method and apparatus for detecting particles in a gas by: the gas is saturated with vapour and caused to flow through a chamber having a wall temperature different from that of the incoming gas, thereby creating a turbulent flow of gas within the chamber, causing the gas to become supersaturated, and causing the supersaturated vapour to condense on particles and form droplets, which are then detected and counted by an optical light scattering detector. However, this method and apparatus cannot detect particles in real time.

WO 2018/010954a1 discloses a device for breath-controlled application of an aerosol in powder form during artificial or assisted breathing of a patient, the system comprising the following elements: the device comprises a mouthpiece, which can be brought into contact with the respiratory tract of a patient for artificial respiration or respiratory support, a unit for generating a flow of respiratory gas, wherein the flow of respiratory gas has a first pressure which is higher than or equal to the atmospheric pressure, at least one inspiratory line through which the flow of respiratory gas is guided to the mouthpiece, an aerosol generator, at least one aerosol line through which the generated aerosol in powder form is guided from the aerosol generator to the mouthpiece, and a respiration sensor.

EP 0539674 a1 discloses an aerosol generator for use as a nebulizer for controllably and reproducibly generating a wet or dry aerosol for inhalation studies, comprising: a nebulizer for generating an aerosol from a liquid flow and a gas flow, a liquid feeding device such as a step-feed pump for controllably feeding the liquid to be nebulized to the nebulizer, an instrument such as a mass flow controller for regulating the gas flow to the nebulizer to provide the required amount of nebulized liquid and optionally diluting the generated aerosol, a conduit for conveying the aerosol formed in the nebulizer to an aerosol exposure chamber, a measuring device such as a light scattering diffusion photometer into which an aerosol sample is introduced to determine the concentration of the aerosol, and a control unit for controlling the liquid supply device and the adjustable air supply to generate an aerosol with a predetermined desired concentration; the control unit may be operated manually or by a computer in response to the measured values determined by the measuring means.

WO 2015/189089 a1 discloses a sensor system for measuring the concentration and mass concentration of particles in an aerosol. Optical sensors are used to measure particle concentration, while mechanical sensors are used to measure the mass of collected particles. The particle concentration in the aerosol is monitored using an optical sensor until a particle generating event is detected. Upon detection of a particle generating event, a mass measurement is performed using the mechanical sensor and used to calibrate the optical sensor.

US 2016/000358 a1 discloses a diagnostic device for characterizing and/or controlling particles from a patient's airways, such as the lungs, when ventilated by a ventilator, the diagnostic device comprising a particle detection unit configured to be connected to a conduit for passing expiratory fluid from the patient to obtain data relating to particles exhaled from the patient's airways.

In addition, known methods and devices for determining the absorption of a liquid (in particular water or an aqueous solution) by particles or the adsorption of a liquid on the surface of particles require chemical analysis of the sample containing the particles, thereby modifying and eventually destroying the particles.

Problems to be solved

It is therefore an object of the present invention to provide a device and a method for determining aerosol delivery of an aerosol flow, which at least partly avoids the above mentioned problems.

In particular, it would be desirable to be able to use a device and method that can determine aerosol delivery of aerosol streams containing liquid or solid particles in real time and for both high and low tidal volumes in a simple and quantitative manner, so as to be suitable for adults, but also for infants, toddlers, neonates and premature infants. It is therefore also desirable to be able to use the assay in the case of a triggered release of particles, in particular in the case of a breath-synchronized triggered release of particles.

In addition, it is desirable to use the device alternatively or additionally for a method of determining the absorption and/or adsorption of a liquid, in particular water or an aqueous solution, on aerosol particles, which method can be performed in real time.

Disclosure of Invention

This problem is solved by a device and a method for determining aerosol delivery of an aerosol flow and a method for determining absorption and/or adsorption of a liquid on aerosol particles having the features of the independent claims. Preferred embodiments which can be realized individually or in any arbitrary combination are the subject matter of the dependent claims.

As used hereinafter, the terms "having," "including," or any grammatical variations thereof, are used in a non-exclusive manner. Thus, these terms may refer to either the absence of other features in the entity described in this context, or the presence of one or more other features, in addition to the features introduced by these terms. For example, the expressions "a has B", "a includes B" and "a includes B" may refer both to the case where no other element is present in a than B (i.e., where a consists exclusively of B), and to the case where one or more other elements are present in entity a than B, such as elements C, and D, or even other elements.

Furthermore, as used below, the terms "preferably," "more preferably," "particularly," "more particularly," "specifically," "more specifically," or similar terms are used in conjunction with the optional features, without limiting the possibilities of alternatives. Thus, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As the skilled person will appreciate, the invention may be implemented by using alternative features. Similarly, features introduced by "in embodiments of the invention" or similar expressions are intended as optional features, without any limitation to alternative embodiments of the invention, without any limitation to the scope of the invention, and without any limitation to the possibility of combining features of the invention introduced in this way with other optional or non-optional features of the invention.

In a first aspect, the invention relates to a device for determining aerosol delivery of an aerosol flow generated by an aerosol generator.

The term "aerosol" is generally used to refer to an aerosolizable material comprising solid or liquid particles of a substance suspended in a gas phase, wherein the particles may in particular be or comprise particles of a pharmaceutical formulation (such as a lung surfactant). To transform the particles into this state, an aerosolizable material, i.e., a powder or liquid solution, is treated in an "aerosol generator" (also referred to as an "aerosolization device") by vibrating mesh or ultrasound to entrain solid or liquid particles into a stream of carrier gas, such as breathing gas. In this state, the particles are preferably distributed throughout the volume of the carrier gas, in particular in a uniform and finely dispersed form. As a result, the aerosol is provided as an "aerosol stream" in which solid or liquid aerosol particles are carried and/or carried by a carrier gas stream. In particular, the aerosol stream may comprise a dry aerosol stream or a wet aerosol stream, wherein the term "wet aerosol" or "humidified aerosol" refers to aerosol particles in which the aerosol particles have absorbed and/or adsorbed liquid on at least one surface thereof. For this purpose, furthermore, the solid particles can be treated in a so-called "humidifier" to produce a humidified aerosol which, in addition to the carrier gas, also contains a relative amount of vapour.

As further used herein, the term "aerosol delivery" refers to providing an aerosol to a predetermined volume, particularly to a patient interface or measurement volume. Here, a "measurement volume" defines a space in which a measurable quantity of aerosol is determined, which space is preferably placed at a location where the aerosol flow passes on its path between the aerosol generator and the patient interface, or, alternatively or additionally, in a shunt leaving the path. As generally used, the term "patient" relates to a person of any age, including in particular children, infants, newborns and premature infants. Furthermore, the term "ventilation" relates to a process in which the movement of breathing gas in the airway of a patient is achieved, in particular by alternating inspiration and expiration steps. In contrast to a normally breathing patient who is able to circulate without any other assistance, a patient who is supported by breathing during spontaneous breathing or mechanical ventilation needs to be provided with breathing gas at least partly from a ventilator through a ventilation circuit. As generally used, "mechanical ventilation" refers to the administration of physiological breathing, in particular in spontaneous hypopneas or their complete failure, partially or completely with external assistance. Furthermore, "respiratory support" refers to support during spontaneous breathing by applying a Continuous Positive Airway Pressure (CPAP) over the entire respiratory cycle, in particular to avoid alveolar collapse during exhalation and smaller breaths. Thus, the patient may adjust parameters including, but not limited to, depth of breath, breathing rate, or air flow, which typically requires the patient to still be able to breathe on their own.

Furthermore, the term "ventilation circuit" refers to a device configured to provide respiratory support or mechanical ventilation for respiratory gases from a ventilator to a patient and from the patient back to the ventilator, thereby excluding the patient's respiratory tract. Further, the term "patient interface" relates to a unit configured to provide a connection between a ventilation circuit and the airway of a patient, which unit is therefore typically located in the vicinity of the patient. For this purpose, the patient interface may be integrated into or attached to a ventilation circuit, wherein the ventilation circuit may typically contain a ventilator and a tube adapted to conduct gas from the ventilator to the patient interface and back. In particular, a suitable mouthpiece, respiratory mask, nasal cannula or tracheal cannula may be part of or attachable to the patient interface. However, other arrangements of patient interfaces are possible.

According to the present invention, aerosol delivery is determined in a measurement volume, wherein "aerosol delivery" refers to a physical quantity of any one of the number, volume or mass of aerosol particles passing through the measurement volume. Alternatively or additionally, when the term "aerosol delivery" is used, the aerosol delivery rate may also be determined by employing the present invention. As generally used, "aerosol delivery rate" refers to a physical quantity of any one of the number, volume, or mass of aerosol particles passing through a measurement volume over a predetermined time interval. For example, aerosol delivery may refer to the quantity, volume, or mass of aerosol particles delivered to a patient interface. Similarly, the aerosol delivery rate may refer to the number, volume, or mass of aerosol particles delivered to the patient interface over a time interval of, for example, one second, one minute, or one hour. However, other kinds of units are also possible.

Further, according to the present invention, the absorption and/or adsorption of liquid on aerosol particles is alternatively or additionally determined, wherein "the absorption and/or adsorption of liquid on aerosol particles" is a physical quantity related to any one of the quantity, surface area, volume or mass of liquid, in particular water or an aqueous solution, which is absorbed by and/or adsorbed on the surface of aerosol particles. For example, water absorption and/or adsorption may refer to the relative volume or mass of water contained by the humidified aerosol particles. However, other kinds of units are also possible.

The device according to the invention therefore comprises:

-a collection unit having a filter configured for collecting aerosol particles carried by an aerosol flow, a first fluid connection point connectable to an aerosol generator, and a second fluid connection point connectable to a breathing simulator configured for simulating tidal breathing;

-at least one measurement volume designed for interacting at least one light beam with aerosol particles carried by an aerosol flow and passing through said measurement volume;

-at least one optical measurement unit designed for generating at least one optical measurement signal from the interaction of the at least one light beam with the aerosol particles passing through the measurement volume; and

at least one evaluation unit, which is designed for determining the aerosol delivery of the aerosol flow from the at least one optical measurement signal.

The device according to the invention therefore comprises a collection unit, at least one measurement volume, at least one optical measurement unit and at least one evaluation unit. The components listed herein above may be separate components. Alternatively, two or more of the components listed above may be integrated into one component. Further, the at least one evaluation unit may be formed as a separate evaluation unit independent of the optical measurement unit, but may preferably be connected to the optical measurement unit for receiving the respective optical measurement signal. Alternatively, the at least one evaluation unit can be integrated completely or partially into the optical measuring unit.

As mentioned above, the collecting unit has a filter configured for collecting aerosol particles carried by the aerosol flow, a first fluid connection point connectable to an aerosol generator, and a second fluid connection point connectable to a breathing simulator configured for simulating tidal breathing. As commonly used, a collecting unit is a device designed for supplying the aerosol flow to a filter for collecting aerosol particles carried by the aerosol flow and subsequently guiding the aerosol flow away from the filter. As generally used, the term "filter" refers to a device capable of collecting particles supplied by an air flow to a filter surface by depositing at least some of the particles on the filter surface facing in the direction of the air flow. Herein, the air flow is supplied by an aerosol generator to which the collection unit may be connected by using a first fluid connection point. Further, by using the second fluid connection point, the collection unit may be connected to a breathing simulator which supports the collection unit to direct the aerosol flow away after it has passed the filter. As generally used, "breathing simulator" relates to a device specifically set up to simulate tidal breathing by successive inhalations and exhalations, such as described in DIN EN13544 cited above. As a result, aerosol particles are deposited on the filter in a manner comparable to particles inhaled by a patient, thus allowing a practical estimation of the aerosol delivery of the aerosol flow available for inhalation by the patient.

According to the invention, the device comprises a collecting unit which can be implemented in a manner as described in DIN EN13544 cited above. Thus, the first fluid connection point may be located in front of the filter with respect to the direction of the aerosol flow, wherein the second fluid connection point may again be located behind the filter with respect to the direction of the aerosol flow and connected to the breathing simulator. For more details, reference may be made to DIN EN 13544. As commonly used, a "fluid connection point" relates to a location in a particular fluid line carrying a flow of gas or aerosol where an additional gas flow can be introduced into or withdrawn from the particular fluid line. In an alternative preferred embodiment, the collecting unit may be based on DE 102013103152B3 and thus have at least one third fluid connection point, which may be connected with an air flow unit for generating an air flow, wherein the third fluid connection point may be arranged such that the aerosol flow may be at least partially guided by the air flow to the filter. For further details, reference may be made to the disclosure of DE 102013103152B 3. However, further embodiments of the collecting unit are conceivable.

Further, according to the invention, the device comprises at least one measurement volume. As generally used, "measurement volume" refers to a volume that extends out of the space set for performing a desired measurement. Herein, the measurement volume is specifically designed for allowing aerosol particles to interact with the at least one light beam (or vice versa), in particular by suitable guidance of the light beam and the particles within the measurement volume. In order to be able to measure all aerosol particles carried by the aerosol flow, the measurement volume may preferably be located between the first fluid connection point and the filter, i.e. upstream with respect to the filter designed for collecting aerosol particles as described above.

The measurement volume is thus designed to allow the aerosol flow to pass through it. In particular, the measurement volume may preferably comprise a wall having an inner surface which may be smooth and as free as possible of edges, recesses and protrusions. As a result, the aerosol flow can thus pass through the measurement volume in a manner that is as little influenced as possible by the form and arrangement of the measurement volume. As described in more detail above, this effect may ensure that as few aerosol particles as possible are deposited on the walls of the measurement volume before depositing the aerosol particles on the filter. In this way, undesired contamination of the measurement volume, in particular of the closing surface of the optical window, which could lead to undesired signal losses of the light beam, can thus be avoided.

As used herein, the term "interaction" refers to the encounter of aerosol particles with a light beam, by which action the light beam may be altered in such a way that the alteration may be related to at least one physical property of the aerosol particles that the light beam encounters as they pass through the measurement volume. As a result, the change of the light beam after encountering an aerosol particle passing through the measurement volume can allow the physical properties of the aerosol particle to be determined, as long as the change of the light beam and the physical properties of the aerosol particle are known. Particularly preferred ways of determining this relationship are described in more detail below.

Further according to the invention, the device comprises at least one optical measurement unit designed to generate at least one optical measurement signal depending on the interaction of the at least one light beam with the aerosol particles passing through the measurement volume. As used herein, an "optical measurement unit" refers to a device having at least one optical sensor configured to generate at least one optical measurement signal by monitoring a change in a light beam, such that, as described above, a physical property of aerosol particles can be determined. As generally used, the terms "optical" and "light" refer to electromagnetic radiation in the visible spectral range, which may also include adjacent infrared and ultraviolet spectral ranges. In case of doubt, with reference to the ISO standard ISO-21348, in the applicable version of the date of the release of this document, the "visible spectral range" generally relates to wavelengths from 380nm to 760nm, whereas the "infrared spectral range" generally refers to wavelengths from 760nm to 1000pm, of which wavelengths from 760nm to 1.4pm are generally referred to as the "near infrared spectral range", whereas the "ultraviolet spectral range" refers to wavelengths from 1nm to 380nm, preferably from 100nm to 380 nm. Preferably, the light used in the present invention is visible light, i.e. light in the visible spectral range having a wavelength of 380nm to 760 nm.

In a particularly preferred embodiment, the change in the light beam monitored by the optical measurement may be the extinction of the light beam in the measurement volume as the aerosol particles pass through. As commonly used, "extinction of a light beam" relates to the attenuation of a light beam occurring within a measurement volume after the light beam encounters one or more aerosol particles. Thus, the extinction level of the light beam results in an optical measurement signal that can be used to determine a desired physical property of the aerosol particles as described in more detail below. Alternatively or additionally, other kinds of changes of the light beam may be measured by the optical measurement unit, such as changes in transmission, absorption, diffraction, reflection, refraction, scattering or polarization of the light beam.

The light beam for interacting with aerosol particles carried by the aerosol flow within the measurement volume may be provided by at least one illumination source arranged to emit at least one light beam for this purpose. Herein, the illumination source may comprise at least one of the following illumination sources: lasers, in particular laser diodes, although in principle alternatively or additionally also other types of lasers can be used; a light emitting diode; organic light sources, in particular organic light emitting diodes; a structured light source. Alternatively or additionally, other illumination sources are also possible.

In a particularly preferred embodiment, the optical measuring unit can be further configured to provide at least one light beam. To this end, the laser measuring unit may be set to provide at least one light beam, in addition to having at least one optical sensor set to generate at least one optical measuring signal by monitoring the change in the light beam. Here, the laser measurement unit is capable of generating at least one laser beam, which may in particular be provided in the form of a single narrow beam, which may pass through the measurement volume in a static or dynamic manner. Preferably, the light beam, in particular the laser beam, may have a small aperture in all directions other than the direction perpendicular to the direction of aerosol flow, thereby allowing monitoring of at least a part of the aerosol particles, preferably all aerosol particles, passing through the measurement volume within a time interval required for the aerosol particles to pass the light beam aperture (aperture) in the direction of aerosol flow. As used herein, the term "perpendicular" refers to a value of 90 °, but may also include a deviation of ± 15 °, preferably ± 5 °, more preferably ± 1 °, in particular ± 0.1 ° from a perpendicular arrangement. Thus, in a particular embodiment, the light beam may be adapted to illuminate a light sheet within the measurement volume, in particular a lamella which may be perpendicular to the direction of the aerosol flow. As generally used, the term "lamellae" refers to a two-dimensional extension of light, rather than one-dimensional extension of light in a beam-like manner.

In a particularly preferred embodiment, the measurement volume can be separated from the optical measurement unit by at least one optical window. As generally used, the term "optical window" refers to a device configured for a light beam to be passed by at least one light beam when entering or leaving the measurement volume. As a result, the optical window can guide the aerosol flow through the measurement volume with as little deviation as possible by letting the light beam enter or leave the measurement volume. Further, in order to influence the light beam as little as possible, the optical window may comprise an optically at least partially transparent material, preferably a material exhibiting a high optical transparency at least one wavelength of the light beam. For this purpose, the optically at least partially transparent material may also be substantially homogeneous and not embedded particles, in particular to avoid undesired signal losses (e.g. caused by scattering of the light beam at the embedded particles). In this context, the optical window and the respective walls of the measurement volume may be provided by the same material or by different materials. Thus, the optical window may be comprised by the wall, or may be provided as a separate unit attached (e.g. by using an adhesive) to the wall from the inside or the outside of the measurement volume.

In another particularly preferred embodiment, the optical windows may be arranged in a pattern in which the light beams can pass through the optical windows in a perpendicular manner. As also used herein, the term "perpendicular" refers to a value of 90 °, but may also include a deviation from perpendicular placement of ± 15 °, preferably ± 5 °, more preferably ± 1 °, in particular ± 0.1 °. Due to this arrangement, further undesired signal losses due to undesired refraction of the light beam entering or leaving the optical window, which may typically exhibit a refractive index different from the refractive index of the at least one substance comprised by the measurement volume, may be at least partially avoided.

In a further particularly preferred embodiment, the optical window can exhibit a thickness which is as small as possible, in order to keep the mechanical stability of the optical window within a desired range. Thus, further undesired signal losses due to attenuation of the light beam through the optical window may be partly avoided.

In a particularly preferred embodiment, the laser beam may be emitted from a laser emitter and pass through a first optical window of the measurement volume towards which preferably aerosol particles are present. By the presence of aerosol particles, the laser beam may be attenuated, may pass through a second optical window located on the opposite side, and may be captured by the laser receiver.

In an alternative embodiment, the light beam may impinge on an opposite side of the measurement volume, where it may be reflected to be guided to the optical measurement unit. Here, the light beam may be reflected in such a way that it may or preferably is not at least partly passed through the measurement volume again. Thus, in a particular embodiment, the light beam may be reflected such that the light beam may take the same path back through the measurement volume and, if applicable, through the optical window to the optical measurement unit. This arrangement may allow an increase of the optical measurement signal by a factor of about 2, thereby increasing the sensitivity of the optical measurement signal.

In a particularly preferred embodiment, the measurement volume can therefore be separated from the optical measurement unit by two opposing optical windows, wherein the two opposing optical windows can be arranged in a parallel manner with respect to one another. As used herein, the term "parallel" refers to a value of 180 °, but may also include a deviation from a parallel arrangement of ± 15 °, preferably ± 5 °, more preferably ± 1 °, in particular ± 0.1 °. Further, it may be advantageous to arrange the two opposing optical windows as close as possible with respect to each other. Although the close arrangement of two opposing optical windows may reduce the sensitivity of the optical measurement signal, at the same time an unnecessary multiple scattering within the measurement volume is increased. In order to reduce signal losses, it may be further advantageous to arrange the illumination source and/or the optical sensor as close as possible to the respective optical window.

In another particular embodiment, the device may additionally comprise a heating unit, which may be configured to heat the at least one optical window. As a result, the at least one optical window may be kept free from any moisture and particle deposits, in particular, thereby avoiding undesired signal losses of the light beam passing through the optical window contaminated by particles and moisture deposits. In particular, the heating unit may be provided in the form of a heating cabinet capable of accommodating the device or at least a part thereof comprising the measurement volume and at least one optical window separating the measurement volume from the optical measurement unit.

In another particular embodiment, the device may comprise two separate measurement volumes. Here, the at least one first optical measurement unit may be designed to generate at least one first optical measurement signal as a function of an interaction of the at least one first light beam with aerosol particles passing through the first measurement volume in an inhalation phase of the breathing simulator, and the evaluation unit may be designed to determine a first aerosol delivery of the aerosol flow in the inhalation phase from the first optical measurement signal. Similarly, the at least one second optical measurement unit may be further designed to generate at least one second optical measurement signal from an interaction of the at least one second light beam with aerosol particles passing through the second measurement volume during the expiration phase, and the evaluation unit may be designed to determine a second aerosol delivery of the aerosol flow during the expiration phase from the second optical measurement signal. Thus, in this particular embodiment, a first aerosol delivery of the aerosol flow during the inhalation phase and a second aerosol delivery of the aerosol flow during the exhalation phase may be separately determined.

Further, according to the invention, the device comprises at least one evaluation unit which is designed to determine the desired information item, i.e. the aerosol delivery of the aerosol flow and optionally the absorption and/or adsorption of liquid on the aerosol particles, from the at least one optical measurement signal. Preferably, in particular for determining a shift caused by absorption and/or adsorption of a liquid, one optical measurement signal may be sufficient for dry aerosol flow, while at least two optical measurement signals may be preferred for wet aerosol flow. As used herein, the term "evaluation unit" refers to a device designed to produce the desired item of information, i.e. aerosol delivery of the aerosol flow from at least one optical measurement signal. For this purpose, the evaluation unit may be or may comprise one or more integrated circuits, for example one or more application-specific integrated circuits (ASICs), and/or one or more data processing devices, for example one or more computers, preferably one or more microcomputers and/or microcontrollers. Further components may be included, such as one or more preprocessing devices and/or data acquisition devices, such as one or more devices for receiving and/or preprocessing sensor signals, such as one or more AD converters and/or one or more filters. As used herein, an optical measurement signal may generally refer to one of the sensor signals. Further, the evaluation unit may comprise one or more data storage means. Further, as mentioned above, the evaluation unit may comprise one or more interfaces, such as one or more wireless interfaces and/or one or more wired interfaces. As mentioned above, the device has at least one evaluation unit. In particular, the at least one evaluation unit may further be designed to control or drive the device completely or partially, in particular by designing the evaluation unit to control the at least one optical measurement unit.

The evaluation unit can be designed to carry out at least one measurement cycle in which one or more optical measurement signals are recorded for further evaluation in the evaluation unit. For this purpose, the at least one evaluation unit may be adapted to execute at least one computer program, in particular by implementing any or all of the method steps described herein. As an example, one or more algorithms can be implemented which can determine the desired information item by using the optical measurement signal as an input variable.

For more details about the device, reference may be made to the description of the device, its exemplary embodiments and methods described herein.

In another aspect, the present invention relates to a method of determining aerosol delivery of an aerosol flow. As used herein, the method comprises the following steps a) to d):

a) providing an aerosol stream generated by an aerosol generator;

b) directing aerosol particles carried by an aerosol flow through at least one measurement volume and providing interaction of the aerosol particles with at least one light beam within said measurement volume;

c) generating at least one optical measurement signal from interaction of the at least one light beam with aerosol particles passing through the measurement volume; and

d) determining aerosol delivery of the aerosol flow from the at least one optical measurement signal, wherein a transfer function between the optical measurement signal and the aerosol delivery is used.

Herein, although the indicated steps may be performed in a given order, preferably all indicated steps may be performed at least partly simultaneously. Other method steps, such as step e), whether described in this document or not, may additionally be performed.

According to step a), providing an aerosol stream, wherein the aerosol stream is generated by an aerosol generator. In this context, the aerosol flow may be a dry aerosol flow or a wet aerosol flow comprising absorbed liquid and/or absorbed liquid, the delivery and/or rate of delivery of which is to be determined by the present method.

According to step b), aerosol particles carried by the aerosol flow are guided through the at least one measurement volume in such a way that the aerosol particles interact with the at least one light beam within the measurement volume.

According to step c), at least one optical measurement signal is generated in such a way that the optical measurement signal, preferably a plurality of optical measurement signals, depends on the interaction of the at least one light beam with the aerosol particles passing through the measurement volume.

According to step d), determining the aerosol delivery of the aerosol flow from the at least one optical measurement signal, wherein for the determination thereof a transfer function between the optical measurement signal and the aerosol delivery is used. For this purpose, a conversion function such as a conversion coefficient may be acquired from a table such as a table stored in a storage device included in the evaluation unit.

Preferably, the transfer function can be determined by performing the following step e) at least once, preferably before step d), also simultaneously with or after step d):

e) collecting aerosol particles carried by an aerosol flow in a filter, measuring the particle loading on the filter; determining the transfer function from a relationship between the particle loading and the at least one optical measurement signal.

According to step e), the collection means comprises a filter for gravimetrically determining the aerosol particle loading. For this purpose, the filter is weighed and then, when inserted into the system, aerosol sampling is started at a first and a second point in time after the aerosol particles have been loaded. As a result, the difference between the second weight measured at the second point in time and the first weight measured at the first point in time allows determining the weight loading of the aerosol particles received by the filter between the first point in time and the second point in time. At the same time, the optical signal of the aerosol particles is determined from at least one optical measurement signal, in particular a plurality of optical measurement signals, recorded at a time interval between the first time point and the second time point. By generating a relationship between the light signal and the weight loading of the same aerosol particles in the same aerosol flow, the conversion factor can be determined. This procedure according to step e) can be repeated several times, if necessary, preferably for different particle loadings, for example by using a regression algorithm, in particular a linear regression, to determine the conversion coefficients with the desired accuracy.

Subsequently, further taking into account the known values of the aerosol flow, a transfer function can be used in step d) without further gravimetric determination of the loading of the aerosol particles according to step e). As a result, preferably, a single gravimetric determination of the loading of aerosol particles is sufficient to determine aerosol delivery of the aerosol stream. However, if desired, the loading of aerosol particles can still be determined gravimetrically at any later point in time.

In another aspect, the present invention relates to a method of determining the absorption and/or adsorption of a liquid, in particular water or an aqueous solution, on aerosol particles. The method comprising steps a) to e) according to the preceding method claim and the following step f):

f) generating at least two optical measurement signals for at least two different particle loadings of the aerosol particles, measuring the at least two different particle loadings of the aerosol particles on at least two different filters, and determining the absorption and/or adsorption of liquid on the aerosol particles from the assumed zero optical measurement signal.

According to step f), the optical measurement signal is measured for at least two different loadings of aerosol particles on at least two different filters, wherein each loading of aerosol particles on at least two different filters is determined, preferably in a gravimetric manner as described in connection with step e). From the optical measurement signal measured for each of the at least two different loadings, an optical measurement signal with zero particle loading on the filter can be inferred by employing a suitable algorithm such as linear regression. For zero particle loading on the filter, this non-negligible extrapolated optical measurement signal is the observation that the optical measurement signal obtained by optical measurement according to the method used herein still contains an additional contribution due to the liquid, in particular water or an aqueous solution, which is absorbed and/or adsorbed on the aerosol particles, whereas gravimetric determination of dry filters only determines the loading of the dry aerosol particles on the filter after removal of any liquid component. In particular, for a hypothetical zero optical measurement signal, the intercept of the negative x-axis corresponds to the mass of liquid, for example in mg, which is absorbed and/or adsorbed on the aerosol particles.

For more details about the method, reference may be made to the description of the apparatus and its exemplary embodiments elsewhere herein.

The device and method according to the invention may thus in particular allow to determine in real time the aerosol delivery of the aerosol flow, and optionally the absorption and/or adsorption of liquid on the aerosol particles, in a simple and quantitative manner, since it is sufficient to perform one single gravimetric determination of the loading of the aerosol particles before the subsequent optical measurements, which may be performed in real time. The method and apparatus for determining aerosol delivery is also applicable to small tidal volumes (which are typical particularly for infants, toddlers, and newborns).

Drawings

In the subsequent description of preferred embodiments, further optional features and embodiments of the invention will be disclosed in more detail, preferably in conjunction with the dependent claims. Wherein the various optional features may be implemented in isolation and in any feasible combination, as will be appreciated by the skilled person. It is emphasized that the scope of the present invention may not be limited by the preferred embodiments. Embodiments are schematically depicted in the figures. In which like reference numbers in the figures refer to identical or functionally comparable elements.

In the figure:

fig. 1A to 1C schematically show three preferred embodiments of a device for determining aerosol delivery of an aerosol flow generated by an aerosol generator;

fig. 2A to 2C show in isometric view (fig. 2A), cross-section from the top (fig. 2B) and cross-section from the side (fig. 2C) a preferred embodiment of a device for determining aerosol delivery of an aerosol flow generated by an aerosol generator;

figures 3A and 3B show a preferred embodiment of the first connector in an isometric view (figure 3A) and a cross-sectional view from the side (figure 3B);

FIGS. 4A and 4B show a preferred embodiment of the first portion of the apparatus in an isometric view (FIG. 4A) and a rear view (FIG. 4B);

FIGS. 5A and 5B show a preferred embodiment of the second partial device in an isometric view (FIG. 5A) and in a cross-sectional view from the top (FIG. 5B);

FIG. 6 shows a preferred embodiment of a laser mount in an isometric view;

figure 7 schematically illustrates a method of determining aerosol delivery of an aerosol flow;

fig. 8 shows the relationship between the optical signal and the weight loading of the aerosol particles.

Detailed Description

Fig. 1A and 1B schematically show two preferred embodiments of a device 110 for determining aerosol delivery of an aerosol flow 112, in particular a dry aerosol flow 112 or a wet aerosol flow 112 containing absorbed liquid and/or absorbed liquid, generated by an aerosol generator 114. As shown in fig. 1A and 1B, the device 110 comprises a collection unit 116, wherein the collection unit 116 has a filter 118 configured to collect aerosol particles 120 carried by the aerosol flow, a first fluid connection point 122 connectable to an aerosol generator, and a second fluid connection point 124 connectable to a breathing simulator 126 (such as a sinusoidal pump 128) configured to simulate tidal breathing.

Further, the device 110 comprises a measurement volume 130, which may preferably be located downstream of the aerosol flow 112 of a region 132 where a patient interface may be placed. In this context, the measurement volume 130 is designed for the interaction of at least one light beam (not shown here) with aerosol particles 120 carried by the aerosol flow 112 and passing through the measurement volume 130. Herein, the measurement volume 130 may be defined by a wall of a conduit 134, the conduit 134 being provided for guiding the aerosol flow 112 from the aerosol generator 114 to the filter 118. In the embodiment shown here, the first fluid connection point 122 is located in front of the filter 118 with respect to the direction of aerosol flow, and the measurement volume 130 is located between the first fluid connection point 122 and the filter 118.

Further, the device 110 comprises an optical measurement unit 136, which is preferably a laser measurement system 138 or comprises a laser measurement system 138, the laser measurement system 138 being designed for generating at least one optical measurement signal depending on the interaction of at least one light beam with the aerosol particles 120 passing through the measurement volume 130. In particular, the optical measurement unit 136 is designed for generating an optical measurement signal depending on the extinction of the light beam in the measurement volume 130 when the aerosol particles 120 pass through the measurement volume 130. However, other ways of generating the optical measurement signal, such as diffraction, reflection, refraction, scattering or polarization of the light beam, are also feasible.

Further, the device 110 comprises an evaluation unit 140, which is designed for determining a desired aerosol delivery of the aerosol flow 112 from the at least one optical measurement signal. In this context, the evaluation unit 140 may be designed for determining the number, volume or mass of aerosol particles 120 passing through the measurement volume 130. Alternatively or additionally, the delivery rate of the aerosol, which refers to the aerosol delivery of the aerosol flow 112 through the measurement volume 130 over a predetermined time interval (e.g., one second, one minute, or one hour), may also be determined.

As schematically depicted here, the evaluation unit 140 may be formed as a separate evaluation unit 140 independent of the optical measurement unit 136, but may preferably be connected to the optical measurement unit for receiving the respective optical measurement signal, e.g. by a wired connection or a wireless communication 142. Alternatively (not shown here), the evaluation unit 140 can be integrated completely or partially into the optical measuring unit 136. As further shown herein, an online-monitorable monitor 144 may be used to present the determined aerosol delivery of the aerosol flow 112. However, other kinds of output means are also feasible.

Fig. 1B shows a further preferred embodiment of the device 110, wherein, in addition to the embodiment shown in fig. 1A, the collection unit 116 has two third fluid connection points 146, which are connected to an air flow unit for generating an air flow 148, wherein the third fluid connection points 146 are arranged in the following manner: the aerosol flow 112 is at least partially directed by the airflow 148 to the filter 118. In the particular embodiment shown in FIG. 1B, a centrifugal pump 150 is used to create a closed loop 152 of gas within the collection unit 116. However, other embodiments of the gas closed circuit are also possible.

Fig. 1C shows another preferred embodiment of the device 110, which contains two separate measurement volumes 130, 130'. In this context, the first optical measurement unit 136 is designed, in a manner similar to the embodiment shown in fig. 1B, for generating at least one first optical measurement signal from the interaction of the at least one first light beam with the aerosol particles 120 passing through the first measurement volume 130 during the inspiration phase, wherein the evaluation unit (not shown here) is designed for determining the first aerosol delivery of the aerosol flow 112 during the inspiration phase from the first optical measurement signal. Herein, the patient interface 132 may be used for the simulation of the inspiratory phase by drawing particles from the patient interface 132 to the filter 118.

In order to further provide a simulation of the expiration phase, the expired aerosol is guided into a separate expiration duct 153, which contains at least one second optical measurement unit 136', which optical measurement unit 136' is also designed for generating at least one second optical measurement signal as a function of the interaction of the at least one second light beam with the aerosol particles 120 that pass through the second measurement volume 130' during the expiration phase, wherein an evaluation unit (not shown here) is designed for determining a second aerosol delivery of the expired aerosol flow from the second optical measurement signal. Hereinafter, aerosol particles are collected in the second filter 118', whereupon a particle-free gas flow 153a may be generated, which may be directed via the device 153b to the adapter 153c to be reintroduced into the aerosol flow 112 provided by the aerosol generator 114, the device 153b generating breathing gas for respiratory support, using for example Continuous Positive Airway Pressure (CPAP), or for mechanical ventilation.

In particular, the embodiment of fig. 1C may be used to determine aerosol delivery in preterm infants, in particular for use with a device for breath controlled aerosol administration as disclosed in, for example, WO 2018/010954a 1. However, other applications of this embodiment are possible.

Fig. 2A to 2C show a preferred embodiment of the device 110 for determining aerosol delivery of an aerosol flow 112 generated by an aerosol generator 114, in isometric view (fig. 2A), in cross-section from the top (fig. 2B) and in cross-section from the side (fig. 2C), but the device 110 is free of a filter 118 and a second fluid connection point 124. In the preferred embodiment, the device 110 is provided in the form of a first sub-device 154, a second sub-device 156, a laser transmitter 158 and a laser receiver 160, with the filter 118 and the second fluid connection point 124 being connected to the second sub-device 156. In this context, the first partial device 154 contains the measurement volume 130 (not visible here), a connection (not shown here) between the first partial device 154 and a first connector 162 comprising the first fluid connection point 122, and the third fluid connection point 146, while the second partial device 156 is a filter 118 and a second connector 164 of the second fluid connection point 124. Further, the optical measuring unit 136 is here provided in the form of a laser measuring system 138, wherein, as shown here, the laser measuring system 138 is divided into a laser transmitter 158 and a laser receiver 160. While laser transmitter 158 is designed to provide a laser beam 166, laser receiver 160 is configured to receive laser beam 166 and generate at least one optical measurement signal based on the interaction of laser beam 166 with aerosol particles 120 passing through measurement volume 130. As is further indicated, an evaluation unit 140 designed for determining the aerosol delivery of the aerosol flow 112 from the at least one optical measurement signal is integrated into the laser receiver 160. However, other embodiments of the evaluation unit 140 as described above are also possible here. Further, the laser measurement system 138 is disposed on a laser mount 168, a preferred embodiment of which is described in more detail below.

Fig. 3A and 3B show a preferred embodiment of the first connector 162 in an isometric view (fig. 3A) and a cross-sectional view from the side (fig. 3B). As already indicated above, the first connector 162 comprises the first fluid connection point 122. As further described herein, first connector 162 includes a connection 170 between first portion device 154 and first fluid connection point 122, where a distance 172 represents a length over which first connector 162 may be introduced into first portion device 154.

Fig. 4A and 4B show a preferred embodiment of the first partial device 154 in an isometric view (fig. 4A) and a rear view (fig. 4B). As already indicated above, the first partial device 154 contains the measurement volume 130, a connection 170 between the first partial device 154 and the first connector 162 and the third fluid connection point 146. As further depicted herein, the first part-means 154 may additionally comprise at least one first recess 174 for receiving a portion of the laser measurement system 138, an optical window 178 set for separating the laser measurement system 138 from the measurement volume 130 and another connection 180 for receiving the laser mount 168.

In general, the optical window 178 is designed such that the aerosol flow 112 can be guided through the measurement volume 130 with as little deviation as possible when the light beam enters or leaves the measurement volume 130. Further, the window 178 is designed such that the light beam passing through the measurement volume 130 at the same time is dispersed as little as possible. For this purpose, the optical window 178 may comprise an optically at least partially transparent material, preferably a material that may exhibit a high optical transparency at least one wavelength of the light beam. Thereby, the optically at least partially transparent material may be substantially homogeneous and free of embedded particles. Further, the optical window 178 may preferably be arranged in such a way that the light beam may pass through the optical window in a perpendicular manner. Further, the optical window 178 may exhibit a thickness as small as possible, thereby maintaining the mechanical stability of the optical window within a desired range.

Further, as shown in the particularly preferred embodiment of fig. 4A and 4B, the measurement volume 130 may be separated from the optical measurement unit 136 by two opposing optical windows 178, which two opposing optical windows 178 may be arranged in a parallel manner with respect to each other. Alternatively, the two optical windows 178 may include an arrangement that is tilted with respect to each other.

Further, it may be advantageous to arrange the two opposing optical windows 178 as close as possible relative to each other. Further, it may be advantageous to arrange the illumination sources and/or the optical sensors of the optical measurement unit 136 as close as possible to the respective optical windows 178. Further, a heating unit, such as a heating cabinet (not shown here), may be provided which may be designed for heating one or both optical windows 178, thereby keeping at least one optical window 178 free from any particle deposits, in particular, thereby avoiding undesired signal losses of the light beam through the optical window 178 contaminated by particle and moisture deposits. However, it is also possible to heat all or other components of the collection unit 116.

Fig. 5A and 5B show a preferred embodiment of the second partial device in an isometric view (fig. 5A) and in a cross-sectional view from the top (fig. 5B). As already described above, the second partial device 156 is designed to provide a connection between the first partial device 154 and the filter 118. For this purpose, the second partial device 156 is preferably embodied as a filter 118 and a second connector 164 of the subsequent second fluid connection point 124. As further depicted herein, the second partial device 156 may thus include another connection 176 to the first partial device 154.

Fig. 6 shows a preferred embodiment of the laser mount 168 in an isometric view. As depicted therein, the laser mount 168 may preferably include another connection 180 to the first partial device 154 and an elongated slot 182, which elongated slot 182 may be designed to provide an adjustable connection to the laser measuring system 138. Distance 184 represents the length of laser mount 168, which preferably may be selected to provide sufficient mechanical stability to laser measurement system 138.

Fig. 7 schematically illustrates a preferred embodiment of a method 200 of determining aerosol delivery of an aerosol stream 112 generated by an aerosol generator 114. Thus, the aerosol stream 112 generated by the aerosol generator 114 is provided as a delivery step 202 in step a). In step b), aerosol particles 120 carried by the aerosol flow 122 are guided through the measurement volume 130, such that in an interaction step 204 the aerosol particles 120 interact with at least one light beam provided within the measurement volume 130. As a result of this interaction, in a measurement step 206 of step c), an optical measurement signal is generated which depends on the interaction of the at least one light beam with the aerosol particles 120 passing through the measurement volume 130. In a determination step 208 of step d), a desired aerosol delivery 210 of the aerosol flow 112 is determined from the recorded optical measurement signal.

For this purpose, a transfer function, in particular a transfer coefficient, between the optical measurement signal and the aerosol delivery can be used here. Herein, the conversion function, e.g. the conversion coefficient, may be obtained from a table, e.g. a table stored in a storage means comprised by the evaluation unit 140. In a particularly preferred embodiment, the transfer function can be determined at least once, preferably once, by performing the calibration step 212 of step e), preferably before step d), and also simultaneously with or after step d). According to step e), aerosol particles 120 carried by the aerosol flow 112 are collected in the filter 118, the resulting particle loading on the filter 118 is measured, in particular the loading measured on the filter 118 is determined gravimetrically, the conversion being determined from the relationship between the particle loading on the filter 118 and the at least one optical measurement signal.

In a particularly preferred example for this measurement, the filter 11 is weighed 8, and when the filter 118 is inserted into the device 110, the aerosol particles 120 are loaded from the beginning at a first point in time until the end at a second point in time. As a result, the difference between the second weight measured at the second point in time and the first weight measured at the first point in time allows the determination of the weight loading of the aerosol particles 120 received by the filter 118 between the first point in time and the second point in time. At the same time, from the optical measurement signals recorded at the time intervals between the first time point and the second time point, the integral of the optical measurement signal of the aerosol particles 120 between the first time point and the second time point is determined. By creating a relationship between the integral of the optical measurement signal and the gravimetrically determined loading of the same aerosol particles 120 within the same aerosol flow 112, a transfer function such as a transfer coefficient may be determined. If desired, the procedure according to step e) may be repeated a plurality of times, preferably for different particle loadings, such as in order to determine the transfer function with the desired accuracy.

Fig. 8 shows a preferred example of the relationship between light signal and weight loading for the same aerosol particles 120. In the diagram 214, the different optical signals S relate to the degree of extinction, such as by:

S＝log(Io/I)，

where Io denotes the intensity of the beam before passing through the measurement volume 130, I denotes the intensity of the beam after passing through the measurement volume, and log denotes the logarithm of any known reference, which is presented in the vertical y-axis relative to the weight loading L mg of the same aerosol particles 120, which in the graph 214 is the measurement point relative to the horizontal x-axis. In particular by applying a linear fitting procedure (e.g. linear regression), a resulting line 216 can be obtained as a relation between the light signal and the weight loading of the same aerosol particles 120. For example, the relationship can be described as follows:

y＝0.0829x+0.0303，

where y relates to the extinction calculated from the magnitude of the optical signal S at the corresponding gravitational loading L at position x on the x-axis. Alternatively or additionally, other programs, such as other regression algorithms, may be applied here to determine the relationship. Alternatively or additionally, other kinds of changes of the light beam, such as changes of diffraction, reflection, refraction, scattering or polarization of the light beam, may be measured by the optical measurement unit 136.

Subsequently, taking further into account the known values of the aerosol flow 112, a transfer function, such as a transfer coefficient, which can be determined in this way can be used in the determination step 208 without repeating the calibration step 212. As depicted above, preferably, a single gravimetric determination of the loading of the aerosol particles 120 is sufficient to determine the aerosol delivery 210 of the aerosol stream 112. However, the calibration step 212 may still be repeated if desired.

Alternatively or in addition to being used for the calibration step 212, the schematic diagram 214 of fig. 8 may also be applied to a method of determining the absorption and/or adsorption of a liquid 220 on aerosol particles 120. As schematically shown in fig. 8, the optical measurement signals are measured in step f) for at least two different loadings of the aerosol particles 120 on the filter 118, wherein each loading of the aerosol particles 120 on the filter 118 is also determined gravimetrically as described above. From the various optical measurement signals shown in fig. 8, the inferred particle loading x of the zero optical measurement signal can be determined by employing the same regression algorithm (e.g., linear regression) as described above₀. In the above example, for y ═ 0, x may be obtained₀A value of-0.36. Thus, the intersection of the linear regression with the negative x-axis may provide a value 218 corresponding to the mass of liquid absorbed and/or adsorbed on the aerosol particle 120, and thus, the mass and/or weight of liquid absorbed and/or adsorbed on the aerosol particle 120 may be determined.

List of reference numerals

110 device

112 aerosol stream

114 aerosol generator

116 collecting unit

118. 118' filter

120 aerosol particles

122 first fluid connection point

124 second fluid connection point

126 breathing simulator

128 sine pump

130, 130' measuring volume

132 patient interface region

134 catheter

136. 136' optical measuring unit

138. 138' laser measuring system

140 evaluation unit

142 are in communication with

144 monitor

146 third fluid connection point

148 air flow

150 centrifugal pump

152 closed loop

153 expiratory conduit

153a particle free gas flow

153b device for generating breathing gas using Continuous Positive Airway Pressure (CPAP) for respiratory support or for mechanical ventilation

153c adapter

154 first part device

156 second part of the device

158 laser transmitter

160 laser receiver

162 first connector

164 second connector

166 laser beam

168 laser mounting rack

170 connection

Distance 172

174 recess

176 additional connection

178 optical window

180 additional connections

182 elongate slot

184 distance

200 method of determining aerosol delivery

202 delivery step

204 interaction step

206 measurement step

208 measurement step

210 aerosol delivery

212 calibration step

214 schematic view

216 line

218 extrapolated measurement signal with zero particle loading

220 method for determining the absorption and/or adsorption of a liquid