WO2017037724A1

WO2017037724A1 - Device, system and method for measuring particle size

Info

Publication number: WO2017037724A1
Application number: PCT/IL2016/050979
Authority: WO
Inventors: Ram Fishler; Josue Sznitman
Original assignee: Ram Fishler; Josue Sznitman
Priority date: 2015-09-05
Filing date: 2016-09-05
Publication date: 2017-03-09

Abstract

Method and system for measurement of particle size, including at least one flow chamber with a measurement volume defined therein, wherein the flow chamber is configured to accommodate a fluid with a plurality of particles, at least one detector, configured to repeatedly measure positions of one or more particles within the measurement volume, and a processor, configured to determine the one or more particles' size based on changes in position of the one or more particles between consecutive measured positions received from the at least one detector, wherein the flow chamber is configured to allow flow in a direction perpendicular to the direction of a force field applied upon the particles.

Description

DEVICE, SYSTEM AND METHOD FOR MEASURING PARTICLE SIZE

FIELD OF THE INVENTION

[001 ] The present invention relates to fluid suspended particles. More particularly, the present invention relates to characterization of fluid suspended particles and to the measurement of particle size.

BACKGROUND OF THE INVENTION

[002] One of many ways to assess a size of a particle is known as aerodynamic size. The aerodynamic size of a particle is defined as the size of a spherical particle of unit density (1000 Kg/m³) that has the same settling velocity as the given particle. This measure of particle size is of major importance in various fields, such as air pollution. In the field of inhaled drug delivery, the aerodynamic size determines to a large extent the efficiency of particle deposition inside the lungs and the spatial distribution of the deposited particles.

[003] A well-established method for measuring aerodynamic particle size distribution is the cascade impactor (CI). CIs are composed of a series of plates with circular holes through which the aerosol is driven. Each of these plates is followed by an impaction plate that collects particles of different aerodynamic diameters according to the flow velocity, the hole diameter and the distance to the impaction plate. Collected particles are then analyzed, by e.g. weighing the plates. Though widely used, CIs are prone to mistakes if the measurement is not done properly. These mistakes stem from particle bouncing from the plates, inter stage losses, error in air velocity measurement etc.

[004] Aerodynamic particle sizers measure aerodynamic size distributions of airborne particles in real-time. This apparatus measures aerodynamic diameter by an optical time-of-flight velocity measurement of aerosol particles that have been accelerated by an accelerating air-flow field. Particle velocity is then correlated to aerodynamic diameter. Sophisticated manipulation of the laser beam is required to create a double crest illumination zone to obtain accurate time of flight measurements and avoid "ghost" particles created by misinterpretation of the light intensity signal. In addition, droplet deformation by the accelerating flow field may cause errors in aerodynamic size estimation.

[005] A direct measurement of particle settling velocity by tracking particle location in a stagnant fluid tank is another way for measuring aerodynamic size. This method has been applied for measuring the settling velocity and aerodynamic size distribution of water-suspended particles by tracking particles using video microscopy. These methods may suffer from bias due to residual flow in the fluid tank. In addition, these methods are limited to particle suspensions that can be brought close to stagnation during a time that is shorter than required for significant loss of particles due to sedimentation and deposition on the tank walls. In particular this method is inadequate for measuring particle size distribution in aerosols (i.e. when the fluid is gas).

[006] Particle aerodynamic size determination of airborne particles can be carried out using image analysis from a series of particle images, e.g. with an automatic sedimentation chamber. However, these methods require a large metal cylinder to ensure no air drift.

SUMMARY OF THE INVENTION

[007] There is thus provided, in accordance with some embodiments of the invention, a system for measurement of particle size, the system including at least one flow chamber with a measurement volume defined therein, wherein the flow chamber is configured to accommodate a fluid with a plurality of particles, at least one detector, configured to repeatedly measure positions of one or more particles within the measurement volume, and a processor, configured to determine the one or more particles' size based on changes in position of the one or more particles between consecutive measured positions received from the at least one detector. In some embodiments, the flow chamber may be configured to allow flow in a direction perpendicular to the direction of a force field applied upon the particles. In some embodiments, the flow chamber may include at least a partially transparent material configured to allow passage of light beams into the flow chamber. In some embodiments, the fluid is a gas.

[008] In some embodiments, the flow chamber may include a conductive material configured to reduce electrostatic particle deposition. In some embodiments, the system may further include an imaging element configured to image the measurement volume, wherein comparison between two consecutive images provides an indication of changes in position of a particle and of the particle size. In some embodiments, the system may further include a light source, configured to emit a light beam towards the flow chamber.

[009] In some embodiments, the system may further include at least one lens, positioned between the light source and the flow chamber, wherein the at least one lens is configured to direct the emitted light beam towards the measurement volume. In some embodiments, the system may further include at least one slit positioned between the light source and the flow chamber, wherein the slit is configured to reduce the width of the light beam passing through the measurement volume.

[0010]In some embodiments, the system may further include a flow control unit configured to control the flow within the flow chamber in order to allow measurements in any one of: laminar flow and under stagnant conditions. In some embodiments, the system may further include at least one valve configured to control flow entrance into the flow chamber. In some embodiments, the system may further include at least one pressure transducer.

[001 l]In some embodiments, the system may further include a filter configured to filter particles of a predetermined parameter. In some embodiments, the system may further include at least one pump. In some embodiments, the source of the particles may be an external aerosol from a medical inhaler. In some embodiments, the system may further include a memory unit operably coupled to the detector and configured to store at least one measurement.

[0012]There is thus provided, in accordance with some embodiments of the invention, a method of measuring particle size, the method including adjusting a flow of particles to pass through a measurement volume at a predetermined flow rate, measuring, by at least one detector, positions of particles within the measurement volume, recording, in a memory, a time stamp for each measurement, determining changes in position of particles between consecutive measurements, and calculating particle size based on the determined changes in position. In some embodiments, the flow of particles may pass in a direction perpendicular to the direction of a force field applied upon the particles.

[0013]In some embodiments, the method may further include imaging, by at least one imager, the measurement volume to produce consecutive images, and comparing at least two consecutive images to determine changes in position of particles.

[0014]In some embodiments, the method may further include directing a light beam towards the measurement volume, wherein the flow of particles passes through the measurement volume. In some embodiments, the method may further include adjusting the light beam with at least one of a slit and a lens.

[0015]In some embodiments, adjusting a flow includes changing the flow rate from a first (e.g., fast) flow rate, e.g., in the range of 0.5-120 liter/minute to a second (e.g., slow) flow rate, e.g., in the range of 0-0.1 liter/minute. In some embodiments, the second flow rate may be zero. In some embodiments, the second flow rate may be constant. In some embodiments, the second flow rate may be time dependent. In some embodiments, the second flow rate may alternate between slower flow rate in the range of 0-0.001 liter/minute and another (faster) flow rate in the range of, for example, 0.005-0.1 liter/minute.

[0016]In some embodiments, the method may further include filtering particles of a predetermined parameter. In some embodiments, the method may further include calculating a linear regression scheme for particle positions. In some embodiments, the method may further include calculating velocity values for at least one particle. In some embodiments, the method may further include calculating aerodynamic diameters of at least one particle.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]The subject matter regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of the specification. The invention, however, both as to organization and method of operation, together with objects, features, and advantages thereof, can best be understood by reference to the following detailed description when read with the accompanying drawings in which:

[0018]Fig. 1A schematically illustrates a cross-sectional view of a particle size determination system, according to some embodiments of the invention;

[0019]Fig. IB schematically illustrates a cross-sectional view of the particle size determination system with an imaging element, according to some embodiments of the invention;

[0020]Fig. 2 schematically illustrates a cross-sectional view of a flow control unit, according to some embodiments of the invention;

[0021]Fig. 3 schematically illustrates a perspective transparent view of a flow chamber, according to some embodiments of the invention;

[0022] Fig. 4 shows a flow chart for a method of measuring particle size, according to some embodiments of the invention; and

[0023]Fig. 5 shows a flow chart for a method of adjusting a flow of particles to pass through a measurement volume at a predetermined flow rate, according to some embodiments of the invention.

[0024]It will be appreciated that, for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements can be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals can be repeated among the figures to indicate corresponding or analogous elements.

DETAILED DESCRIPTION OF THE INVENTION

[0025]In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention can be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention. [0026]Measurement of particles suspended in a fluid allowing on-line measurement of aerodynamic particle size distributions is described herein. In particular measurement and determination of particle size distributions of dense aerosols such as cigarette smoke or inhalation devices including dry powder inhalers, metered dose inhalers, and nebulizers in the aerodynamic diameter range of over about 0.3 μπι. It should be noted that the term 'particle' relates herein to either liquid droplets and/or solid dust particles, and that the fluid may be either gas or liquid.

[0027] Reference is now made to Figs. 1 A-1B. Fig. 1A schematically illustrates a cross-sectional view of a particle size determination system 100 where the cross-section is carried out along 'XY' plane, according to some embodiments of the invention. A fluid with suspended particles may be delivered via a channel 101, for example an aerosol from a medical inhaler, sample with particles to be measured. It should be appreciated that only the outlet of channel 101 is shown in Fig. 1A.

[0028]In various embodiments, particle size determination system 100 may include at least one flow chamber 104 such that the flow of fluids within which the particles to be measured are suspended may be directed into the flow chamber 104. In some embodiments, the direction of the flow is along the longitudinal axis 'X'. In some embodiments, particle size determination system 100 may further include mechanical and/or electrical mechanisms configured to direct the fluid and particles into flow chamber 104, and/or additional flow mechanism to control the fluid flow rate.

[0029]In various embodiments, flow chamber 104 may include at least partially transparent material 102 configured to allow passage of light, e.g. for illumination and visualization of samples within flow chamber 104. In some embodiments, at least one outlet channel 103 may be used to direct the fluid from flow chamber 104 into a flow control unit 200, as further described in Fig. 2.

[0030]In various embodiments, a force field may be applied in the direction Ύ' which is perpendicular to the flow direction 'X'. This force field may be caused by gravitation, centrifugal force, electrostatic force, magnetic force, thermo-kinetic force, ultrasound-induced force, a combination thereof or any other force capable of creating particle motion in the Ύ' direction.

[0031] In various embodiments, particle size determination system 100 may include at least one detector 106 configured to measure positioning of particles in the fluid in at least two time instances during the passage of the particles through the flow chamber 104, for example along at least one spatial axis (e.g. the 'Υ' direction parallel to the force field). In some embodiments, such measurement of particle positions may be carried out in conjunction with determining the time between consecutive measurements, thereby indicating properties of these particles.

[0032] It should be appreciated that particle size determination system 100 may include computational elements (not shown in the figures) that may enable processing of measured data, for example data measured with detector 106. In some embodiments, a processor and/or controller may be operably coupled to detector 106. Such a processor and/or controller may be operably coupled to a memory unit capable of storing measurement data such as particle positions in at least two different time instances, e.g., with a time stamp. In some embodiments, a particle size determination algorithm, for example executed on the processor, may allow determination of particle size and/or aerodynamic diameter based on the data measured by e.g. detector 106. For example, use detector 106 to capture locations of particles within flow chamber 104, in order to perform data processing (e.g., using particle size determination algorithm) to calculate terminal velocity of each particle and thereby determine the particle sizes.

[0033]In some embodiments detection of particle locations may be performed using an illumination element and/or an imaging element as described in Figs. 1A-1B. It should be noted that such measurement may be used in addition to or instead of detector 106,

[0034]It should be appreciated that illumination of the samples within flow chamber 104 may be carried out with a collimated light source 105 from which a narrow light beam 10 may pass towards flow chamber 104, for example along a transversal axis Y (perpendicular to longitudinal axis 'X'). It should be noted that light source 105 may be external to flow chamber 104, such that light beam 10 passes through the at least partially transparent material 102 and into flow chamber 104. In some embodiments, the light source 105 may be a laser diode capable of producing light beams 10 at a wavelength of about 450 nm.

[0035]The light beam 10 may pass through at least one lens 107 (e.g., a cylindrical lens) that is configured to expand light beam 10 so as to illuminate a predetermined measurement volume 109 within flow chamber 104. In some embodiments, light beam 10 may further pass through at least one narrow slit 108, in order to create a light sheet by reducing the width of the light beam 10, e.g. in the 'Z' direction perpendicular to 'XY' plane (as shown in Fig. IB), thus reducing noise due to out of focus particles.

[0036] In some embodiments, particle size determination system 100 may not include lens 107 for example if the width of the light beam 10 is larger and/or equal to the width of the measurement volume 109 in the X' direction. [0037]Fig. IB schematically illustrates a cross-sectional view of the particle size determination system 100 with an imaging element 117, where the cross-section is carried out along ΎΖ' plane, according to some embodiments of the invention. It should be noted that the cross- sectional plane ΎΖ' in Fig. IB is perpendicular to the cross-sectional plane 'XY' in Fig. 1A, such that fluid within flow chamber 104 may flow away from the reader in Fig. IB.

[0038]In various embodiments, particle size determination system 100 may further include at least one imaging element 117 that may be configured to be positioned adjacent to flow chamber 104 and perform imaging thereon. For instance, imaging element 117 positioned to be aligned with, and perform imaging at, predetermined measurement volume 109. In some embodiments, imaging element 117 may include at least one microscope objective (e.g., with additional lenses) and configured to allow particle imaging using at least one photosensitive apparatus, such as a camera. In some embodiments, particle size determination system 100 may include two flow chambers 104 and two corresponding imaging systems and/or interchangeable lens in order to cover a wide range of particle sizes (e.g., if one of the flow chambers is limited to detect particles of a predetermined size).

[0039]It should be appreciated that measured optical data as well as data that allows calculation of time between consecutive measurements may be transferred to the processor, for instance to carry out image analysis according to the time of measurements. In some embodiments, the time period between measurements may be a predetermined parameter of the particle size determination system 100, or alternatively the measurement time (e.g., time between consecutive measurements) may be recorded for each pair of consecutive images separately. In some embodiments, imaging element 117 may determine a set of particle locations, for example within measurement volume 109, at least at two time instances as well as the time between consecutive measured images.

[0040] In some embodiments, a single image, for instance captured with imaging element 117 at a relatively long exposure time, may capture a set of particle locations appearing as a line or streak in the image. Such a streak, along with the predetermined exposure time may include data of particle location at least for two time points, for example corresponding to the start-point and end-point of the streak.

[0041]In some embodiments, collimated light source 105 together with at least one of lens 107 (e.g., cylindrical) and slit 108 may illuminate the predetermined measurement volume 109 by creating a light sheet parallel to the direction of gravitational force (along the transversal axis Ύ) and perpendicular to the viewing direction of imaging element 117 (the transversal axis 'Z'). To form such light sheet, the angular orientation of the lens (if present) may be aligned to expand the collimated light beam 10 in the plane that is parallel to the fluid flow ('XY' as shown in Fig. 1A). In some embodiments, slit 108 may be oriented so as to reduce the width of the light sheet in the direction parallel to the viewing direction of imaging element 117 ('Z' as shown in Fig. IB).

[0042] According to some embodiments, imaging element 117 may include at least one camera (e.g., a video camera) for example equipped with at least one microscope objective and additional lenses, and aerodynamic diameters of particles may be calculated by determining the location of particles in the imaging plane 'XY' (e.g., as shown in Fig. 1A). Such calculation may be performed for instance using image analysis techniques configured to compare images, thus obtaining locations in two-dimensional images for at least two different time points. In some embodiments, locations of particles in a captured image may be determined for example by locating the intensity weighted centroid for a set of neighboring pixels having intensity above a predetermined threshold value. In some embodiments, two locations in consecutive images may be identified as pertaining to the same particle by assuming that closest particles in consecutive frames represent the same particle.

[0043]It may be appreciated that since the particles are optically measured using light source 105 and/or imaging element 117, there is no need for sample dilution even for very dense aerosols, in contrast to some commercially available solutions. Thus, complicated and costly dilution systems are not required and measurement errors due to inhomogeneous dilution may be avoided.

[0044]It should be noted that the velocity component in the direction perpendicular to the flow direction and parallel to the force field (the Ύ' direction) may be assessed by averaging the distance in the Ύ direction traveled between pairs of consecutive measurements of the same particle and dividing by the time period between consecutive images. Such averaging may increase measurement accuracy and may also reduce errors due to Brownian motion for smaller particles. It should be noted that the direction of the force field being perpendicular to the direction of the flow may allow measuring aerodynamic diameter with no dependency on the flow rate in the 'X' direction.

[0045]In some embodiments, if the flow velocity is constant, the velocity component in the direction perpendicular to the flow direction and parallel to the force field (in the Ύ direction) may be calculated by adopting a linear regression scheme and calculating the best fitting line between all measured locations for a certain particle. It should be appreciated that by determining the slope of the regression line and the flow velocity (for example calculated according to the average particle velocity in the 'X' direction) the Ύ' component of particle velocity may be calculated.

[0046]In some embodiments of the invention, the calculated Ύ' component of particle velocity may be used to calculate the aerodynamic diameter of a particle. It should be noted that under conditions where fluid flow in the 'Υ' direction is negligible, a force balance on a particle in the 'Υ' direction may be assumed between the external force applied by the force field (e.g. gravity) and the buoyant force combined with stokes drag force. Under these conditions, the 'Υ' component of particle velocity is equal to the terminal velocity, u_t, and the aerodynamic diameter, d_p, may be calculated from equation 1 :

where μ is the viscosity of the fluid, p_p is the density of the particle (e.g. assumed to be 1000 Kg/m³), pf is the density of the fluid, a is the free fall acceleration of the force field (e.g. the standard acceleration due to gravity), and C_c is the Cunningham correction factor for the drag force.

[0047]In some embodiments, constructing a count-weighted distribution of aerodynamic diameters may be possible from the set of determined aerodynamic diameters. It should be noted that a mass-weighted distribution of particle aerodynamic sizes may be obtained by assuming that particles are spherical and have a constant effective density. In some embodiments, for example in cases where the illuminated volume is wider than the depth of focus of the imaging system, a correction of particle count per volume (or density) can be applied based on particle size to compensate for the fact that smaller out of focus particles may not be detected. Such a correction may be done either with mathematical considerations or measurement of samples of known density. In some embodiments, for better accuracy, correction factors for particle shape and/or particle mass density may be used, where each of these factors may be a constant and/or a function of aerodynamic diameter.

[0048]In some embodiments, such calculation of particle sizes (for example using particle size determination system 100) may be compared to commercially available chemical measurements of the particles. For instance carrying out simultaneous measurements for the same particles in both systems and comparing the results.

[0049] Reference is now made to Fig. 2, which schematically illustrates a cross-sectional view of the flow control unit 200, according to some embodiments of the invention. The flow control unit 200 may include at least one of a syringe pump 201 , an automatic valve 202 (e.g. a solenoid valve), a regulating valve 203 (e.g. a needle valve), a filter 204 and a vacuum pump 205, with fluid connection therebetween. In some embodiments, flow control unit 200 may further include at least one pressure transducer 206 adjacent to regulating valve 203.

[0050] According to some embodiments, flow control unit 200 may initially draw fluid at a relatively high velocity into flow chamber 104, and at a certain time the flow rate may be decreased to allow accurate measurements of particle locations in measurement volume 109.

[0051]In some embodiments, prior to an initial measurement automatic valve 202 may be switched such that no air is drawn from flow chamber 104 (e.g., as shown in Fig. 1A). Upon initiation of the measurement, automatic valve 202 may be switched so as to open passage of fluid from the flow chamber 104 to the vacuum pump and allow fluid to be drawn from flow chamber 104 at a predetermined flow rate (e.g., at a rate of 60 liter/minute for some dry powder inhalers). It should be noted that such relatively high initial flow rate may be required both to allow correct operation of dry powder inhalers and to allow homogeneous filling of the flow chamber 104 with particles.

[0052]In some embodiments, the automatic valve may be switched at a predetermined time so as not to allow flow from the flow chamber 104 to the vacuum pump 205. At this stage the syringe pump, located upstream to the automatic valve may exclusively control the flow rate in flow chamber 104, and this flow rate may be reduced compared to initial flow, completely stopped or alternated between lower (e.g., in the range of 0-0.001 liter/minute) and higher (e.g., in the range of 0.005-0.1 liter/minute) values. It should be noted that reducing the flow rate compared to the initial flow may be necessary in order to obtain accurate measurements of particle locations as well as determination of the Ύ component of velocity. It should be further noted that alternating the flow velocity between lower (e.g., in the range of 0-0.001 liter/minute) and higher (e.g., in the range of 0.005-0.1 liter/minute) values may allow increasing the amount of measured particles by quickly replacing the particles under observation.

[0053] It should be appreciated that the flow rate initially drawn by the vacuum pump may be set by adjusting regulating valve 203 before the measurement and measuring the flow rate entering flow chamber 104, for instance using a flow meter.

[0054] In some embodiments, pressure transducer 206 may be used to maintain ratio of absolute pressure (e.g., gas pressure) upstream and downstream of regulating valve 203, for example to be larger than 2, in order to assure that limiting pressure is reached within flow chamber 104. It should be appreciated that under such conditions pressure variations downstream of the regulating valve do not affect the flow rate in the flow chamber.

[0055]In some embodiments, the automatic valve 202 may be a two-way valve completely blocking or opening passage of fluid from flow chamber 104 to the vacuum pump. [0056]In some embodiments, the automatic valve 202 may be a three-way valve that may be switched between two states: a fluid passage from flow chamber 104 to the vacuum pump may be closed and fluid passage from ambient fluid (e.g. air) to the vacuum pump may be opened; or fluid passage from flow chamber 104 to the vacuum pump 205 may be opened and fluid passage from the ambient fluid to the vacuum pump may be closed.

[0057]In some embodiments, the aerosol leaving the regulating valve is filtered using e.g. a glass microfiber filter before entering the vacuum pump.

[0058]In some embodiments, flow control unit 200 may include filter 204 being positioned at any various locations along flow control unit 200, for example between automatic valve 202 and regulating valve 203. In some embodiments, flow control unit 200 may not include any pressure transducers 206.

[0059] In some embodiments, flow control unit 200 may include at least one valve closing the passage into syringe pump 201 when the passage into vacuum pump 205 is open. In some embodiments, syringe pump 201 may be located upstream to flow chamber 104. It should be appreciated that while a syringe pump 201 is described above, any other type of controllable pump may also be used.

[0060]According to some embodiments, flow control unit 200 may include a single syringe pump 201 to control the flow. According to some embodiments, flow control unit 200 may include a single automatic regulating valve to control the flow.

[0061] Reference is now made to Fig. 3, which schematically illustrates a perspective transparent view of the flow chamber 104, according to some embodiments of the invention. In some embodiments, particles may be introduced to the entire cross-sectional area of flow chamber 104.

[0062]In some embodiments, flow chamber 104 may include at least two transparent panels 304 that when combined may form a rectangular channel. In some embodiments, flow chamber 104 may include four transparent panels 304. In some embodiments, such a channel (or chamber) may be fluidly connected to at least one connector 302 positioned at the channel outlet and/or inlet. In some embodiments, the panels 304 may also be conductive and/or coated with a conductive material at least from one side so as to reduce electrostatic deposition of particles on the inner chamber walls.

[0063] According to some embodiments, at least one connector 302 may include an opening 301 (e.g., circular) to which the fluid and fluid suspended particles may be introduced. In some embodiments, connector 302 may provide a smooth transition between opening 301 and the rectangular channel, and thereby avoid abrupt disturbances to the flow. It should be noted that such a structure may ensure substantially laminar flow patterns in flow chamber 104, such that particles may homogeneously fill the volume of flow chamber 104 thereby minimizing bias in aerodynamic size distribution measurements.

[0064]In some embodiments, the structure of flow chamber 104 may allow laminar streamlines that are substantially parallel to the chamber walls in most of the flow chamber including measurement volume 109 thereby minimizing measurement bias due to convective particle transport in a direction perpendicular to the flow direction.

[0065]According to some embodiments, flow chamber 104 may include a flow chamber with a circular cross-section, or any other polygonal cross-section. In some embodiments, addition of a sheath flow, for example of a clean fluid, from a wider inlet may improve performance by reducing particle deposition on the chamber walls as well as reduction of gradual loss of accuracy in measurements.

[0066] According to some embodiments, flow chamber 104 may be positioned so that the flow direction may be perpendicular to the force field applied onto the fluid, for example if the force field is gravity (applying force in vertical direction) then flow chamber 104 may be positioned horizontal relative to the surface of the Earth. It should be noted that in this configuration flow velocity in the 'X' direction (e.g., as shown in Fig. 1A) may not affect the measurement of particle velocity in the direction perpendicular to the flow direction.

[0067]In some embodiments, opening 301 may be connected to an external aerosol source (e.g. inhaler), for instance through an adult Alberta idealized throat (AIT). In some embodiments, opening 301 may be connected to the external aerosol source through an induction port similar to the one used in cascade impactors (CIs). In some embodiments, opening 301 may be connected to the external aerosol source through a straight tube.

[0068]Reference is now made to Fig. 4, which shows a flow chart for a method of measuring particle size, according to some embodiments of the invention. According to some embodiments, the method includes adjusting 401 a flow of particles to pass through a measurement volume 109 at a predetermined flow rate, for example within flow chamber 104 (e.g., as shown in Figs. 1A-1B).

[0069]In some embodiments, the method further includes measuring 402 positions of particles within the measurement volume, for example measuring with detector 106 and/or imaging element 117 (e.g., as shown in Figs. 1A-1B). In some embodiments, the method further includes recording 403 a time stamp for each measurement.

[0070]In some embodiments, the method further includes determining 404 changes in position of particles between consecutive measurements, for example between two consecutive images captured with imaging element 117. In some embodiments, the method further includes calculating 405 particle size based on the determined changes in position. In some embodiments the method further includes calculating count weighted distributions and/or mass weighted distributions of aerodynamic diameter.

[0071] Reference is now made to Fig. 5, which shows a flow chart for a method of adjusting a flow of particles to pass through a measurement volume at a predetermined flow rate, according to some embodiments of the invention. It should be appreciated that the method described in Fig. 5 may include additional embodiments for carrying out the adjustment 401 described in Fig. 4.

[0072]According to some embodiments, the method may include filling 501 a flow chamber 104 with particles in an initial high first flow rate (e.g., in the range of 0.5-120 liter/minute). In some embodiments, the method may further include reducing 502 the flow rate of the fluid to a low second flow rate (e.g., in the range of 0-0.1 liter/minute). In some embodiments, the method may further include directing 503 the fluid towards the measurement volume 109. It should be appreciated that by adjusting the flow rate from a fast rate to a slow rate, it may be possible to homogeneously fill the chamber with particles and then correctly measure particle locations in the fluid.

[0073]Unless explicitly stated, the method embodiments described herein are not constrained to a particular order in time or chronological sequence. Additionally, some of the described method elements can be skipped, or they can be repeated, during a sequence of operations of a method.

[0074]Various embodiments have been presented. Each of these embodiments can of course include features from other embodiments presented, and embodiments not specifically described can include various features described herein.

Claims

1. A system for measurement of particle size, the system comprising:

at least one flow chamber with a measurement volume defined therein, wherein the flow chamber is configured to accommodate a fluid with a plurality of particles;

at least one detector, configured to repeatedly measure positions of one or more particles within the measurement volume; and

a processor, configured to determine the one or more particles' size based on changes in position of the one or more particles between consecutive measured positions received from the at least one detector,

wherein the flow chamber is configured to allow flow in a direction perpendicular to the direction of a force field applied upon the particles.

2. The system of claim 1, wherein the flow chamber comprises at least a partially transparent material configured to allow passage of light beams into the flow chamber.

3. The system of claim 1, wherein the flow chamber comprises a conductive material configured to reduce electrostatic particle deposition.

4. The system of any one of claims 1-3, further comprising an imaging element configured to image the measurement volume, wherein comparison between two consecutive images provides an indication of changes in position of a particle and of the particle size.

5. The system of any one of claims 1 -4, further comprising a light source, configured to emit a light beam towards the flow chamber.

6. The system of claim 5, further comprising at least one lens, positioned between the light source and the flow chamber, wherein the at least one lens is configured to direct the emitted light beam towards the measurement volume.

7. The system of claim 5, further comprising at least one slit positioned between the light source and the flow chamber, wherein the slit is configured to reduce the width of the light beam passing through the measurement volume.

8. The system of claim 1 , further comprising a flow control unit configured to control the flow within the flow chamber in order to allow measurements in any one of: laminar flow and under stagnant conditions.

9. The system of claim 8, further comprising at least one valve configured to control flow entrance into the flow chamber.

10. The system of claim 8 or 9, further comprising at least one pressure transducer.

11. The system of any one of claims 8-10, further comprising a filter configured to filter particles of a predetermined parameter.

12. The system of any one of claims 8-11, further comprising at least one pump.

13. The system of claim 1, wherein the source of the particles is an external aerosol from a medical inhaler.

14. The system of any one of the preceding claims, further comprising a memory unit operably coupled to the detector and configured to store at least one measurement.

15. The system of claim 1 , wherein the fluid is a gas.

16. A method of measuring particle size, the method comprising:

adjusting a flow of particles to pass through a measurement volume at a predetermined flow rate;

measuring, by at least one detector, positions of particles within the measurement volume;

recording, in a memory, a time stamp for each measurement;

determining changes in position of particles between consecutive measurements; and calculating particle size based on the determined changes in position,

wherein the flow of particles passes in a direction perpendicular to the direction of a force field applied upon the particles.

17. The method of claim 16, further comprising:

imaging, by at least one imager, the measurement volume to produce consecutive images; and

comparing at least two consecutive images to determine changes in position of particles.

18. The method of claim 17, further comprising directing a light beam towards the measurement volume, wherein the flow of particles passes through the measurement volume.

19. The method of claim 18, further comprising adjusting the light beam with at least one of a slit and a lens.

20. The method of claim 16, wherein adjusting a flow comprises changing the flow rate from a first flow rate to a second flow rate.

21. The method of claim 20, wherein the first flow rate is in the range of 0.5-120 liter/minute, and the second flow rate is in the range of 0-0.001 liter/minute.

22. The method according to any one of claims 20 and 21 , wherein the second flow rate is zero.

23. The method according to any one of claims 20 and 21 , wherein the second flow rate is constant.

24. The method according to any one of claims 20 and 21 , wherein the second flow rate is time dependent.

25. The method of claim 20, wherein the second flow rate alternates between a slower flow rate in the range of 0-0.001 liter/minute and faster flow rate in the range of 0.005-0.1 liter/minute.

26. The method of claim 16, further comprising filtering particles of a predetermined parameter.

27. The method of claim 16, further comprising calculating a linear regression scheme for particle positions.

28. The method of claim 16, further comprising calculating velocity values for at least one particle.

29. The method of claim 16, further comprising calculating aerodynamic diameters of at least one particle.