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Schematic illustration of (A) the prototype system with an expanded view of the flow chamber design (inset) and (B) a cross-section through the flow chamber Figure 1 4 cm 1.5mm Slit Flow chamber Induction port Microscope Solenoid valve Needle valve Camera Pressure gauges HEPA filter Vacuum pump Laser Mirror Syringe pump Flow chamber Slit Microscope Laser Induction port A y z x B y z for obtaining APSD measurements from OIPs based on direct estimation of particle settling velocities using image analysis. While conceptually similar methods have been previously reported for determining settling velocities of particles in water 8, 9 or air, 10 this novel method is designed specifically for OIP characteriza- tion and includes means for particle sampling and simultaneous analysis of multiple particles. The simple principle of operation, which was recently patented (#PCT/IL2016/050979), offers few sources of vari- ability, suggesting that this method has the potential for giving reproducible results across different designs and manufacturers as well as machine operators. Furthermore, the system is designed to sample aerosols from the inhaler with no need for dilution, even for the densest aerosols, thereby circumventing any dilution-related measurement biases. As a proof-of-concept, APSDs have been obtained from two widely used commercial dry powder inhalers (DPIs). These measurements are compared to previously published measurements from CIs and the APS. In addition, the article discusses directions for future work and foreseeable improve- ments for the current design, in anticipation of broadening its applicability. Design Figure 1 shows a schematic, computer-aided (CAD) illustration of the prototype design. The following is a brief description of the measurement steps. To begin, a flow meter is attached to the induction port, the vacuum pump is turned on and the flow rate is adjusted, using the needle valve, to the desired rate, based on the specific inhaler (e.g., 60 L/min). Two pressure gauges, located on each side of the needle valve, are used to ensure limiting flow conditions through the valve (i.e., a pressure ratio larger than two). Note that the induction port used in the cur- rent prototype is made of a straight tube (length 22 cm, inner diameter 21.5 mm) rather than an L- shaped throat, in order to maximize the number of measured particles. Next, an inhaler is attached to the induction port and primed according to the manufacturer's instructions. An experiment is initi- ated when the solenoid valve is opened through a remote, computer-controlled signal for approxi- mately 0.1 seconds, drawing the particles into the transparent flow chamber (Figure 1A inset). The rec- tangular flow chamber is comprised of four glass plates, which are plated with ITO (a conductive and transparent material) to reduce electrostatic particle deposition. Once the solenoid valve is shut and the aerosol bolus reaches a near-stop, the particles within the chamber are imaged at a horizontal angle, using a 4X microscope and a fast camera (Figure 1, parts A and B) operating at 166 frames per second (fps) to create a set of 30 consecutive frames. Following the experiment, automatic image analysis, based on particle tracking techniques, is used to determine the aerodynamic diameter of the imaged particles, based on their settling velocities. These measurements are converted to a mass-weighted size distribution by assuming a spherical shape of the particles and a homogenous density that may give rise to sources of error in ensuing measurements when compared to other techniques. During imag- ing, the particles inside the flow chamber are illumi- nated using a thin laser sheet created by a laser diode (450 nm, 100 mW) and a 100 µm wide optical slit (Figure 1B). Using the Fresnel diffraction equation for calculation, the intensity of light inside the cam- era's field of view (FoV) is below 10% of the maxi- mal intensity at a distance of 63 µm from the mid- plane of the laser sheet. Therefore, only particles that are in the vicinity of the imaging plane of the micro- scope are illuminated (Figure 1B) while stray light from out-of-focus particles is attenuated. Note that the slender design of the flow chamber (inner 22 JUNE 2017 Inhalation