Effect of Air Flow and Acceleration on Particle Size of Dry Powder Aerosols determined by Time-of-Flight Aerosol Beam Spectrometry

ABSTRACT

The effect of air flow and acceleration on the particle size distributions of two Turbuhalers containing drug loads of 0.5 and 1.3 mg per dose was determined with a time-of-flight aerosol beam spectrometer (Aerosizer®). While the particle size of both inhalers decreased with increasing flow and acceleration, the distributions became narrower and variability was reduced. Simultaneously, a decrease in the number and mass of particles measured was observed which was more pronounced for the 1.3 mg dose. Additionally the count rate for the 1.3 mg dose was lower than for 0.5 mg. These observations were accompanied by a remarkably fine particle size distribution for the high dose Turbuhaler®. It was concluded that the quantity of particles in the DPI aerosols exceeded the resolution of the Aerosizer, erroneously shifting the size distributions towards smaller diameters.

In addition, the DPI aerosols were analyzed with a Four Stage Impinger to evaluate the results. The particle size estimates obtained using the impinger were in the same range as those obtained at an acceleration of 5 L/s2 using the Aerosizer to study the 0.5 mg Turbuhaler. The Aerosizer produced significantly smaller particle sizes than the impinger in all cases evaluating the 1.3 mg Turbuhaler, supporting the theory of distorted particle size distributions due to particle overload.     

Numerical investigation of powder dispersion mechanisms in Turbuhaler and the contact electrification effect

Powder dispersion in dry powder inhalers (DPI) is affected by factors such as device design and flow rate, but also electrification due to particle–particle/device collisions. This work presented a CFD-DEM study of powder dispersion in Turbuhaler®, aiming to understand the effect of electrostatic charge on the dispersion mechanisms. The device geometry was reconstructed from CT-scan images of commercial Turbuhaler device. Different work functions were applied to the active pharmaceutical ingredient (API) powder and the device wall. Electrostatic charges were accumulated on the API particles due to contact potential difference (CPD) between the particles and the device wall. Results showed that both the chamber and the spiral mouthpiece played an important role in de-agglomeration of powders caused by particle–wall impactions. With increasing flow rates, the performance of the device was improved with higher emitted dose (ED) and fine particle fractions (FPF). The electrostatic charging of the particles was enhanced with higher CPD and higher flow rates, but the electrostatic charging had a minimum effect on powder dispersion and deposition with slight reduction in ED and FPF. In conclusion, the van der Waals force is still the dominant adhesive inter-particle force, and the dispersion efficiency is affected by the flow rate rather than contact electrification of particles. Future work should focus on the effect of highly charged particles emitted from the inhaler on the deposition in the airway.     

Inversion of multiwavelength Raman lidar data for retrieval of bimodal aerosol size distribution

We report on the feasibility of deriving microphysical parameters of bimodal particle size distributions from Mie-Raman lidar based on a triple Nd:YAG laser. Such an instrument provides backscatter coefficients at 355, 532, and 1064 nm and extinction coefficients at 355 and 532 nm. The inversion method employed is Tikhonov's inversion with regularization. Special attention has been paid to extend the particle size range for which this inversion scheme works to approximately 10 microm, which makes this algorithm applicable to large particles, e.g., investigations concerning the hygroscopic growth of aerosols. Simulations showed that surface area, volume concentration, and effective radius are derived to an accuracy of approximately 50% for a variety of bimodal particle size distributions. For particle size distributions with an effective radius of < 1 microm the real part of the complex refractive index was retrieved to an accuracy of +/- 0.05, the imaginary part was retrieved to 50% uncertainty. Simulations dealing with a mode-dependent complex refractive index showed that an average complex refractive index is derived that lies between the values for the two individual modes. Thus it becomes possible to investigate external mixtures of particle size distributions, which, for example, might be present along continental rims along which anthropogenic pollution mixes with marine aerosols. Measurement cases obtained from the Institute for Tropospheric Research six-wavelength aerosol lidar observations during the Indian Ocean Experiment were used to test the capabilities of the algorithm for experimental data sets. A benchmark test was attempted for the case representing anthropogenic aerosols between a broken cloud deck. A strong contribution of particle volume in the coarse mode of the particle size distribution was found.     

Nicotine-loaded chitosan nanoparticles for dry powder inhaler (DPI) formulations – Impact of nanoparticle surface charge on powder aerosolization

The aim of this study is to demonstrate the role of surface charge of nicotine loaded or unloaded chitosan (CS) nanoparticles on the dispersibility from dry powder inhaler (DPI) formulations. The nanoparticles were prepared using glutaraldehyde crosslinking of the amino groups of chitosan in a water-in-oil emulsion. Using dynamic light scattering (DLS) the particle size, size distribution and the zeta potential of nanoparticles were measured. The morphological characteristics were studied using SEM. The fine particle fractions (FPFs) of nanoparticles were determined by a twin stage impinger (TSI) using a Rotahaler at 60?L/min flow rate. The FPF of nanoparticles could be correlated to the surface charge i.e., FPFs were increased with increasing surface charge, which reduced with increased concentration of the drug. The FPF from the large carrier (lactose) based formulations was significantly higher (p?<?0.001) than those of formulations without carriers. The higher FPF from the large carrier-based formulations was independent of zeta potential and thought to be associated with high impaction. These results suggested the mechanism of nicotine loaded CS nanoparticle dispersion without large carriers was dependent on the zeta potential, which was linked to the agglomeration or deagglomeration behaviour of particles.     

Removing 20 nm ceramic particles using a supersonic particle beam from a contoured Laval nozzle

Cryogenic particle beam is an effective means of removing nano-sized contaminant particles from a substrate. To overcome the current cleaning limit of 50 nm, a particle beam with novel properties - smaller bullet size moving at a higher velocity - was used. Argon or Ar/He mixture was expanded through contoured Laval nozzles of various expansion angles to generate extremely small particles through genuine nucleation and growth. Argon particles smaller than 100 nm - smaller by a factor of 10 or more than the conventional Argon aerosols - were successfully generated, and could perfectly remove various ceramic particles down to 20 nm.     

超音速火焰喷涂过程中粒子运动特性的数值模拟

热喷涂涂层质量很大程度上是由颗粒沉积时的状态决定,颗粒不仅受到粒径尺寸的影响,还与飞行过程中焰流特性密切相关.本文以JP8000型超音速火焰喷涂系统(HVOF)喷涂过程为研究对象,采用计算流体动力学方法探究不同氧油质量比下焰流行为和计算域内的燃烧特性;分析不同粒径的颗粒在焰流场内的轨迹特性和速度、温度演变规律,依据数值模拟结果优化工艺参数.计算结果表明:氧油比为3时,HVOF系统内焰流温度最高、速度最快,表明氧油充分燃烧;颗粒注入后可能与枪管壁发生碰撞,且其粒径越大,碰撞发生的临界入射速度越小,碰撞后的粒子会二次穿越焰流中心;颗粒粒径越大,受焰流作用时加热、加速越缓慢,在喷枪内到达的最高温度和最大速度越小.     

Size-dependent aerosol penetration through facemasks and respirators (FMRs) during simulated exhalation and cough

Despite a good understanding of the filtration properties of various face and nose coverings during aerosol inhalation, their effectiveness in reducing aerosol emitted by infected individuals during exhalation or coughing is not fully characterized. This paper presents experiments conducted using a silicone model of a standardized face for controlled flow patterns (steady flow, typical exhalation or flow pulses associated with coughing/sneezing) used to push test aerosols (0.5–20 μm) through valved or non-valved respirators, surgical masks and cloth masks. The aerosol characteristics determined during experiments allowed quantitative comparison of size-dependent aerosol penetration for different flow conditions. The results showed that only aerosols smaller than 8.5–10 μm more easily penetrated beyond the face coverings tested but their concentrations outside were significantly reduced. Calculations based on experimental data showed that the amount of emitted airborne particles that can be inhaled into the lower respiratory tract of bystanders was reduced 1.3–5.7 times compared to the case when the spreader does not use a mask. These results bring additional quantitative information on the role of selected masks and respirators in reducing aerosol emission that potentially contribute to the transmission of viral diseases, including COVID.     

Formulation and evaluation of insulin dry powder for inhalation

PURPOSE: Dry powder formulation of insulin for pulmonary administration was prepared to obtain increased drug deposition in the alveolar absorptive region. The deposition was studied by investigating the dispersion and deaggregation of insulin from the carrier lactose using an Andersen cascade impactor and twin stage impinger. The subsequent absorption following the deposition was studied by in vivo method. METHODS: Insulin in solution with absorption promoters was lyophilized. The powder was incorporated with lactose of different grades and their combinations as carriers to deliver using an inhaler device. Solid-state characteristics of the carrier as well as the drug powder were assessed by particle size and distribution measurement. The flow properties such as moisture content, powder density, angle of repose, and carr's compressibility index of the powder mixture were determined. The aerosol behavior of the powder was studied by dispersion using rotahaler(c) connected to a twin-stage impinger (TSI) and an eight-stage Andersen cascade impactor (ACI) operating at different flow rates of 30-90 l/min. The in vivo performance was studied by deliverance to the respiratory tract of guinea pigs. The intratracheal bioavailability with respective to intravenous route was calculated by measuring the blood glucose reduction. RESULTS: The coarser particles of lactose in fractions of carrier containing a wide particle size distribution impacted in the preseperator of cascade impactor, and only the particle less than 10 microm size entered stage 0-stage 7. Formulation containing 1:1 mixture of Respitose ML006 (62%<50 microm) and Respitose ML003 (37.8%<50 microm) as carrier imparts well deaggregation of insulin, and higher deposition leads to 52.3% of fine particle fraction at 60 Lit/min and in vivo bioavailability of 82%. CONCLUSIONS: Insulin formulations containing 1:1 mixture of Respitose ML006 and Respitose ML003 as carrier can impart deeper deposition of drug particles and cause higher bioavailability. This suggests that carrier used in the formulation influenced the amount of insulin deposition in the alveolar region of the lung. Hence, it was concluded that the availability of insulin for systemic absorption depends on the particle size of the drug as well as the carrier lactose.     

Experimental methods for measuring the optimum amount of dispersant for seven Sumitomo alumina powders

Seven Sumitomo alumina powders of different surface areas and particle size distributions were studied with a view to determining the optimum amount of dispersant (Darvan 821A) required to stabilise aqueous suspensions prepared from the powders. Three different techniques were used; sedimentation, particle sizing and acoustophoresis. Acoustophoresis proved to be the most accurate and quickest way of establishing the optimum amount. It was also shown that the optimum amount of dispersant (0.59mg/m2/) required to stabilise the different sized alumina powders was independent of thepowder surface area/size. Sedimentation results demonstrated that the larger particles acted like hard spheres with thin double layers and gave a smaller relative sediment height than the small particles under the same conditions, i.e. volume fraction and electrolyte strength. This was because the small particles acted as soft spheres with thick double layers that resulted in the particles keeping far apart from one another and hence giving a larger sediment volume.     

Dose assessment for inhalation intakes in complex, energetic environments: experience from the US Capstone study

Because of the lack of existing information needed to evaluate the risks from inhalation exposures to depleted uranium (DU) aerosols of US soldiers during the 1991 Persian Gulf War, the US Department of Defense funded an experimental study to measure the characteristics of DU aerosols created when Abrams tanks and Bradley fighting vehicles are struck with large-caliber DU penetrators, and a dose and risk assessment for individuals present in such vehicles. This paper describes some of the difficulties experienced in dose assessment modelling of the very complex DU aerosols created in the Capstone studies, e.g. high concentrations, heterogeneous aerosol properties, non-lognormal particle size distributions, triphasic in vitro dissolution and rapid time-varying functions of both DU air concentration and particle size. The approaches used to solve these problems along with example results are presented.     

羰基铁粉改性环氧树脂/乙基纤维素微胶囊的吸波性能

以羰基铁粉为吸波剂用溶剂蒸发法制备出环氧树脂/乙基纤维素微胶囊,使用矢量网络分析仪、激光粒度分析仪、ESEM-EDS和FTIR分别表征了微胶囊的吸波性能、粒径分布、颗粒特性以及化学结构。结果表明：羰基铁粉嵌入乙基纤维素中物理结合成微胶囊壁材,羰基铁粉提高了微胶囊的吸波性能。羰基铁粉的粒径越小与电磁波相互作用的面积越大,微胶囊的吸波性能越好。频率为18 GHz时,未掺羰基铁粉的微胶囊电磁波反射损失为-1.63 dB,而掺入粒径为3 μm和0.5 μm羰基铁粉(掺量50%)的微胶囊电磁波反射损失分别为-5.08 dB和-5.44 dB,分别降低了3.45 dB和3.81 dB。掺入粒径为0.5 μm羰基铁粉的微胶囊不团聚,其微观形貌更好。     

Appropriate selection of an aggregation inhibitor of fine particles used for inhalation prepared by emulsion solvent diffusion

Abstract

Context: Dry powder inhaler (DPI) formulations have been developed to deliver large amounts of drugs to the lungs.

Objective: Fine particles of a poorly water-soluble drug, the model drug ONO-2921, were prepared by the emulsion solvent diffusion (ESD) method for use in a DPI.

Methods: The effects of additives on the fine particle formation of ONO-2921 were estimated when droplets of an ethanolic drug solution were dispersed into aqueous media containing various additives. Subsequently, the suspensions were freeze-dried to create powdered samples to estimate the inhalation properties using a twin impinger and an Andersen cascade impactor.

Results: This simple ESD method produced submicron-sized ONO-2921 particles (approximately 600?nm) in combination with suitable additives. In addition, the freeze-dried powder produced using additives exhibited superior in vitro inhalation properties. Among these methods, the freeze-dried powder produced with 0.50% weight/volume one type of polyvinyl alcohol (PVA-205) displayed the most efficient features in the fine particle fraction (FPF). These results could be explained by the stabilization of the ONO-2921 suspension by PVA-205, indicating that PVA-205 acts as an aggregation inhibitor of fine particles.

Conclusions: The ESD method, in combination with appropriate types and amounts of additives, may be useful for preparing a DPI suitable for delivering drugs directly to the lungs without the assistance of carrier particles.     

Multi-scale study of particle flow in silos

The flow characteristics of solid particles in a silo were studied experimentally and theoretically. A multi-scale study of the particles flow was performed by means of discrete element method (DEM). The dependence of flow behaviors on the particles diameter distribution and silo geometry was analyzed to establish the spatial and statistical distributions of microdynamic variables related to flow and silo structures such as velocity, porosity, coordination number, and interaction forces between particles. The results show that the distribution of particle diameter has great effects on particles flow, and the mixing of multi-sized particles is propitious to granular flow. The geometry of silos has greater effects on granular flow than particle size distribution, and inserts can improve the flow behaviors of “funnel flow” type to “mass flow”. Linear equations can be used to describe the relationship between discharge rate and orifice size by G^2/5 vs. D_o for the same distribution of particles diameter. The flow structure of particles in the silos is spatially non-uniform, which is illustrated by spatial and statistical distributions of porosity and coordination number. Both porosity and coordination number are affected by the mode of particles packed, which is affected by the geometry of silos and particle size distribution. The distribution of contact forces between particles is spatially non-uniform too. In flat-bottomed silo, there are arched stress chains in the vicinity of the orifice under the “bridging action”, which disappeared in wedge-shaped hopper silo.     

Automated single-particle SEM/EDX analysis of submicrometer particles down to 0.1 microm

Typically single-particle SEM/EDX analysis of aerosols is done on polycarbonate filters or solid carbon substrates. This has led to a widespread conclusion that EDX provides poor information on carbon, oxygen, and nitrogen content of a particle and usually could not go below 0.5-microm particles. We show that use of grid-supported carbon films of 15-25-nm thickness gives exceptionally low background in the SEM/EDX analysis and allows satisfied automated analysis of particles down to 0.1-microm size, including detection of low-Z elements. In this work, six laboratory-generated 0.1-2-microm aerosols were tested for their elemental composition. The EDX analysis yields reasonably accurate quantitative results featuring all the elements present in the tested compounds, namely, C, O, N, Na, S, Al, Si, and Cl. Furthermore, the carbon film has very low backscattered electron (BSE) yield compared to that from the particle, so in the BSE mode the particle image is seen with very high contrast. This greatly improves quality and speed of the automated mapping of particles by SEM prior to EDX analysis.     

Influence of formulation and preparation process on ambroxol hydrochloride dry powder inhalation characteristics and aerosolization properties

The objective of this study is to evaluate the influence of formulation and preparation process on ambroxol hydrochloride (AH) dry powder inhalation (DPI) characteristics and aerosolization properties. Spray-dried samples of AH, AH/leucine, and AH/leucine/mannitol were prepared from their corresponding water solutions under the same conditions to study the influence of the composition, and the AH/leucine/mannitol (2.5/0.5/1 by weight) formulation was used for investigation of the effect of the preparation process. Following spray-drying, the resulting powders were characterized using scanning electron microscopy, laser diffraction, tapped density, and angle of repose measurements, and the aerosolization performance was determined using a twin-stage liquid impinger. AH/leucine/mannitol (2.5/0.5/1 by weight) obtained by cospray-drying improved the AH aerosolization properties. The AH/leucine/mannitol (2.5/0.5/1 by weight) preparation exhibited the following properties: 62.34% yield, 0.34 g/cm(3) tap density, 2.71 microm d(ae), 33.45 degrees angle of repose, and 30.93% respirable fraction. The influence of the preparation process on DPI characteristics and aerosolization properties was relatively small, but the influence of the composition was relatively large. Optimization of DPI can be achieved by selecting the most appropriate formulation and preparation process.     

Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs

Conventional suspension pressurized metered dose inhalers (pMDIs) suffer not only from delivering small amounts of a drug to the lungs, but also the inhaled dose scatters all over the lung regions. This results in much less of the desired dose being delivered to regions of the lungs. This study aimed to improve the aerosol performance of suspension pMDIs by producing primary particles with narrow size distributions. Inkjet spray drying was used to produce respirable particles of salbutamol sulfate. The Next Generation Impactor (NGI) was used to determine the aerosol particle size distribution and fine particle fraction (FPF). Furthermore, oropharyngeal models were used with the NGI to compare the aerosol performances of a pMDI with monodisperse primary particles and a conventional pMDI. Monodisperse primary particles in pMDIs showed significantly narrower aerosol particle size distributions than pMDIs containing polydisperse primary particles. Monodisperse pMDIs showed aerosol deposition on a single stage of the NGI as high as 41.75?±?5.76%, while this was 29.37?±?6.79% for a polydisperse pMDI. Narrow size distribution was crucial to achieve a high FPF (49.31?±?8.16%) for primary particles greater than 2?µm. Only small polydisperse primary particles with sizes such as 0.65?±?0.28?µm achieved a high FPF with (68.94?±?6.22%) or without (53.95?±?4.59%) a spacer. Oropharyngeal models also indicated a narrower aerosol particle size distribution for a pMDI containing monodisperse primary particles compared to a conventional pMDI. It is concluded that, pMDIs formulated with monodisperse primary particles show higher FPFs that may target desired regions of the lungs more effectively than polydisperse pMDIs.     

Formulation and Evaluation of Insulin Dry Powder for Inhalation

Abstract

Purpose. Dry powder formulation of insulin for pulmonary administration was prepared to obtain increased drug deposition in the alveolar absorptive region. The deposition was studied by investigating the dispersion and deaggregation of insulin from the carrier lactose using an Andersen cascade impactor and twin stage impinger. The subsequent absorption following the deposition was studied by in vivo method. Methods. Insulin in solution with absorption promoters was lyophilized. The powder was incorporated with lactose of different grades and their combinations as carriers to deliver using an inhaler device. Solid-state characteristics of the carrier as well as the drug powder were assessed by particle size and distribution measurement. The flow properties such as moisture content, powder density, angle of repose, and carr's compressibility index of the powder mixture were determined. The aerosol behavior of the powder was studied by dispersion using rotahaler^© connected to a twin-stage impinger (TSI) and an eight-stage Andersen cascade impactor (ACI) operating at different flow rates of 30–90 l/min. The in vivo performance was studied by deliverance to the respiratory tract of guinea pigs. The intratracheal bioavailability with respective to intravenous route was calculated by measuring the blood glucose reduction. Results. The coarser particles of lactose in fractions of carrier containing a wide particle size distribution impacted in the preseperator of cascade impactor, and only the particle less than 10 µm size entered stage 0–stage 7. Formulation containing 1:1 mixture of Respitose ML006 (62%<50 µm) and Respitose ML003 (37.8%<50 µm) as carrier imparts well deaggregation of insulin, and higher deposition leads to 52.3% of fine particle fraction at 60 Lit/min and in vivo bioavailability of 82%. Conclusions. Insulin formulations containing 1:1 mixture of Respitose ML006 and Respitose ML003 as carrier can impart deeper deposition of drug particles and cause higher bioavailability. This suggests that carrier used in the formulation influenced the amount of insulin deposition in the alveolar region of the lung. Hence, it was concluded that the availability of insulin for systemic absorption depends on the particle size of the drug as well as the carrier lactose.     

Intermethod comparison of the particle size distributions of colloidal silica nanoparticles

There can be a large variation in the measured diameter of nanoparticles depending on which method is used. In this work, we have strived to accurately determine the mean particle diameter of 30–40 nm colloidal silica particles by using six different techniques. A quantitative agreement between the particle size distributions was obtained by scanning electron microscopy (SEM), and electrospray-scanning mobility particle sizer (ES-SMPS). However, transmission electron microscopy gave a distribution shifted to smaller sizes. After confirming that the magnification calibration was consistent, this was attributed to sample preparation artifacts. The hydrodynamic diameter, d _h , was determined by dynamic light scattering (DLS) both in batch mode, and hyphenated with sedimentation field flow fractionation. Surprisingly the d _h were smaller than the SEM, and ES-SMPS diameters. A plausible explanation for the smaller sizes found with DLS is that a permeable gel layer forms on the particle surface. Results from nanoparticle tracking analysis were strongly biased towards larger diameters, most likely because the silica particles provide low refractive index contrast. Calculations confirmed that the sensitivity is, depending on the shape of the laser beam, strongly size dependent for particles with diameters close to the visualization limit.     

The Prediction of the Emissivity and Thermal Conductivity of Powder Beds

The particle size distribution and packing (loose bulk and tapped density) of a mixture of ground biomass from Douglas fir wood particles was characterized by different practical methods: sieving, digital imaging and scanning electron microscopy. The ground mixture was analyzed using a set of 14 wire mesh sieves. The calculated mean diameter of mixture was 251 µm. The mixture was divided into four size fractions of mean size ranging from 74 to 781 µm. Particle length measured by imaging technique were 3–4 times larger than the mean diameter determined by sieve analysis. Similarly, particle width was 1.0–2.5 times larger than mean particle diameter. The sphericity of particles in each of the four fractions increased with decreasing size of the sieve indicating that smaller particles also have a smaller aspect ratio. Empirical power law equations were developed to correlate the packing and flow ability of ground particles (HR) to the mean diameter, with R² values of 0.88 and 0.91, respectively. The HR values indicated good flow ability for the large particles and poor flow ability for the smallest particles and the entire mixture. HR and porosity ratio reached an asymptote for particles larger than 400 µm.     

Measurement of 100 nm and 60 nm Particle Standards by Differential Mobility Analysis

The peak particle size and expanded uncertainties (95 % confidence interval) for two new particle calibration standards are measured as 101.8 nm ± 1.1 nm and 60.39 nm ± 0.63 nm. The particle samples are polystyrene spheres suspended in filtered, deionized water at a mass fraction of about 0.5 %. The size distribution measurements of aerosolized particles are made using a differential mobility analyzer (DMA) system calibrated using SRM^® 1963 (100.7 nm polystyrene spheres). An electrospray aerosol generator was used for generating the 60 nm aerosol to almost eliminate the generation of multiply charged dimers and trimers and to minimize the effect of non-volatile contaminants increasing the particle size. The testing for the homogeneity of the samples and for the presence of multimers using dynamic light scattering is described. The use of the transfer function integral in the calibration of the DMA is shown to reduce the uncertainty in the measurement of the peak particle size compared to the approach based on the peak in the concentration vs. voltage distribution. A modified aerosol/sheath inlet, recirculating sheath flow, a high ratio of sheath flow to the aerosol flow, and accurate pressure, temperature, and voltage measurements have increased the resolution and accuracy of the measurements. A significant consideration in the uncertainty analysis was the correlation between the slip correction of the calibration particle and the measured particle. Including the correlation reduced the expanded uncertainty from approximately 1.8 % of the particle size to about 1.0 %. The effect of non-volatile contaminants in the polystyrene suspensions on the peak particle size and the uncertainty in the size is determined. The full size distributions for both the 60 nm and 100 nm spheres are tabulated and selected mean sizes including the number mean diameter and the dynamic light scattering mean diameter are computed. The use of these particles for calibrating DMAs and for making deposition standards to be used with surface scanning inspection systems is discussed.