© Malvern Panalytical 2018

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Ayça DENiZ

Satış Mühendisi / Sales EngineerKimya Mühendisi / Chemical Engineerayca@atomikateknik.com GSM: +90 549 806 20 24

© Malvern Panalytical 2018

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Morphologi 4 Portfolio

21 March 20193

Morphologi 4 & Morphologi 4-ID

Particle size range

0.5 μm – 1300 μm

Particle size range for chemical ID 1 μm – 1300 μm

What is automated particle imaging?

› Measurement of size and shape by capturing 2D images of the individual particles

From the 2D image, we can work out a number of different parameters…

Measure size in up to 2 dimensions e.g. length and width

Measure shape parameters based upon images e.g. aspect ratio = width/length

length

width

Automated Image Analysis: Measurement process

How does it work?

Sample presentation

Static Dynamic

Image capture

Results generationImage processing

Automated image analysis

› Morphologi G4/G4-ID (0.5mm to 1300mm)▪ Flexible static imaging for dry,wet and membranes

▪ Options including chemical identification (G4-ID)

› Dynamic - where the samples are suspended and flow through the imaging system.- This makes for very quick measurements- However, it limits the particle size range

› Static imaging is more flexible in terms of the sample prep, it can be- Entirely dry dispersions using air pressure- Evaporative dispersions- Wet dispersions- FiltersThis gives static imaging a wider dynamic range, but it is a slower technique.

› It also opens up the possibility to do chemical identification

Traditional methods

9

SAMPLE PRESENTATION

Sample presentation: Dispersion

› Good dispersion is critical to good shape information▪ Good particle separation and particle count

› Optimised for sample type▪ Dry, wet, evaporative etc.

Morphologi G4: Dry dispersion

› Sample dispersed by positiveair pressure

▪ 0.5 to 5bar

▪ Default low and high energy

settings are available

Morphologi G4: Evaporative dispersion

› Mix a small amount of sample with solvent into a vial

› Cover a clean microscope slide with ~0.5ml of suspension

› Allow solvent to evaporate and use 4 slide holder

Morphologi G4: Wet dispersion in oil

› Add a small amount of sample to oil in a vial› Place a drop onto a clean microscope slide

Morphologi G4: Wet dispersion, slide with coverslip

› Wet Dispersion – Wet analysis▪ Fine suspended particles such as Nasal spray

▪ Pipette small volume onto microscope slide

▪ Spread out with coverslip

Morphologi G4: Thin path wet cell

› Two quartz plates separated by 25μm spacer› Takes ~250μl of sample

600 800 1000 1200 1400 1600

Raman Shift (cm-1)

No

rmal

ize

d I

nte

nsi

ty

Cellulose

Silicone Oil

Protein

Aggregate

IMAGE CAPTURE

Morphologi G4: Image capture, overlap

› Without any overlap▪ Particles on the edge of

the frame are lost

Morphologi G4: Image capture, overlap

› Without any overlap▪ Particles on the edge of the

frame are lost

› With Overlap▪ Particles edge killed in one

frame are captured in the next frame

▪ XY co-ordinates of all particles recorded so particle 1 is counted in frame A and ignored in frame B

▪ Particle 2 is the largest particle that can be measured as it’s almost as large as the overlap

Image capture and analysis

› Capture 3D digital image of particle› Binarise 2D image using threshold› Calculate size and shape parameter

3D particle 2D particle Converted

to a circle

with the

same area

CE diameter

RESULTS

0 0.24 Elongation 0.79 0.82 0.83

Morphological shape descriptors: Elongation

› Symmetrical shapes have an elongation of 0› Needles and rods have elongation approaching 1› Elongation is not sensitive to edge roughness

𝐸𝑙𝑜𝑛𝑔𝑎𝑡𝑖𝑜𝑛 = 1 −𝑤𝑖𝑑𝑡ℎ

𝑙𝑒𝑛𝑔𝑡ℎ

Morphological shape descriptors: Convexity

› Measure of edge roughness, 1= perfectly smooth› Not sensitive to form, such as elongation

𝐶𝑜𝑛𝑣𝑒𝑥𝑖𝑡𝑦 =𝑐𝑜𝑛𝑣𝑒𝑥 ℎ𝑢𝑙𝑙 𝑝𝑒𝑟𝑖𝑚𝑒𝑡𝑒𝑟

𝑝𝑒𝑟𝑖𝑚𝑒𝑡𝑒𝑟

Convexity 0.59 0.69 0.96 1

Morphological shape descriptors: Circularity

› Measure of closeness to a perfect circle› Perfect circle has a circularity of 1› Sensitive to both form and edge roughness

𝐶𝑖𝑟𝑐𝑢𝑙𝑎𝑟𝑖𝑡𝑦 =𝐶𝐸 𝑝𝑒𝑟𝑖𝑚𝑒𝑡𝑒𝑟

𝑝𝑒𝑟𝑖𝑚𝑒𝑡𝑒𝑟

Circularity 0.35 0.5 0.64 0.67 0.89 1

Morphological shape descriptors: Intensity

Mean intensity

thin vs thick

SD of light intensity

smooth vs rough

Morphological shape descriptors: Summary

› Particle size▪ Circular equivalent (CE) diameter

▪ Length

▪ Width

› Particle form𝐴𝑠𝑝𝑒𝑐𝑡 𝑟𝑎𝑡𝑖𝑜 =

𝑤𝑖𝑑𝑡ℎ

𝑙𝑒𝑛𝑔𝑡ℎ

𝐸𝑙𝑜𝑛𝑔𝑎𝑡𝑖𝑜𝑛 = 1 −𝑤𝑖𝑑𝑡ℎ

𝑙𝑒𝑛𝑔𝑡ℎ

› Particle outline▪ Convexity (perimeter)

▪ Solidity (area)

› Combination of form and outline▪ Circularity/HS circularity

CE

diameter

Result interpretation: Individual particle detail

Size Parameters

Circular equivalent diameter 134μm

Length 290μm

Width 67μm

Control: easy method definition

• New Sharp Edge particle detection mode• Simplified method development

• Better operator control of chemical

analysis • Improved sensitivity to weak Raman scatterers

and thermally sensitive samples

• Fully enclosed system• Minimizes contamination

• Enables measurement of light-sensitive

samples

Definition: enhanced edge

detection

29

Sharp Edge

Thresholding

Sharp Edge

Thresholding

• Improved sample differentiation

• Enhanced image quality • Higher resolution camera

• LED lighting

• Better shape definition• New Sharp Edge particle detection

Definition: enhanced edge

detection

30

• Sharp Edge

• More complete view of the sample

• Enhanced shape definition of high

intensity particles

Definition: increased sensitivity

31

Better definition of low contrast particles

Sharp EdgeThresholding

CASE STUDIES

Metal injection moulding powders

Gypsum

Pharmaceuticals

Abrasives

Understanding product performance: Dissolution

› Different batches showed differing dissolution ▪ Lower convexity – higher surface area

▪ Increased surface area – faster dissolution

Shape analysis of a nasal spray

› Scattergram of circularity vs elongation identifies two populations▪ API and excipient

Excipient

API

PSD of API

What is the Morphologi G4-ID?

Combines automated imaging and Raman spectroscopy in

one integrated platform

Morphologically directed raman spectroscopy

The seamless combination of precise particle size

and shape data with the chemical identification

delivered by MDRS gives you the power to unlock

complex particle characterization problems such as

determining Component-specific morphology,

contaminant Identification.

What is the Morphologi G4-ID?

› Measures 3 key particle properties

› Particle size

› Particle shape

› Chemical identity

Morphologi G4-ID automates your workflow

› Automated sample presentation

› Automated particle imaging

› Automated particle size/shape distribution

› Automated chemical ID

› Automated classification using size/shape/ID

*The automated classification of particles using size, shape and chemical ID

© Malvern Panalytical 2018

MDRS workflow

21 March 201939

Morphologically-Directed Raman Spectroscopy

Sample presentation Image capture

Image processingResults generation Chemical analysis

Morphologi G4-ID hardware

› Morphologi G4 and Kaiser RamanRxn1TM

▪ Fully integrated control

▪ Optical fibre coupled

› Imaging specifications▪ Full capabilities of Morphologi G4

▪ Dry powder dispersion option

› Raman specifications▪ 785nm laser

▪ 3mm dia. spot size with 50x

objective

▪ Spectral range 150cm-1-1850cm-1

▪ 4cm-1 resolution

The Morphologi G4 hardware

consists of two major

components, a modified

version of the Morphologi G4

and

a Kaiser optical systems

RamanRxn1 Raman

spectrometer coupled together

via fibre optic cables.

The instrument software

provides fully integrated

control of both components.

Why you may need Morphologi G4-ID

› Need to know the chemical identity of a class of particles ▪ e.g. presence of certain minerals in cement

› Need to measure the particle size/shape of ingredients in a blend ▪ e.g. drug in nasal spray or dry powder inhaler

› Size and shape characterization still does not solve your problem ▪ e.g. manufacturing troubleshooting

› Manual targeting of particles for Raman measurements takes too long

Morphologi G4-ID sample types

› Dry powders▪ Morphologi G4-ID includes integrated dry powder

sample dispersion

› Wet suspensions▪ High purity quartz microscope slides with coverslip

▪ Analyse dry by evaporation onto microscope slide

▪ Thin path wet cell

• Standard wet cell not compatible

› Filter membranes▪ Depends upon suitability of filter substrate and particle

size/shape (>> 20mm and regular shaped particles)

▪ Quartz filters (7um holes)

HOW THE

MORPHOLOGI

G4-ID WORKS

How the Morphologi G4-ID works

› Sample presentation▪ Automated for dry powders and granules

▪ Raman compatible wet dispersion

› Morphological measurement▪ Automated imaging

▪ Automated particle size and shape

▪ Automated size and shape classification

› Chemical measurement ▪ Automated Raman spectroscopy

▪ Automated chemical ID

▪ Automated chemical classification

Automated dry dispersion, powders & granules

› Can control dispersion pressure, injection time and settle time –

optimize and automate sample

presentation

Goal - good particle separation and

particle count without breaking/modifying

particles of interest

Sample presentation – other options

› Wet samples ▪ Raman compatible slide and

coverslip

▪ Suitable for small particulates

( 20mm

▪ Limited by flatness of filter

Morphological measurement – data analysis

› Images and position of every particle

› Statistical distributions of size and shape

Chemical measurement – particle selection

› Manual user selection▪ Select images and right click

› Automatic particle selection▪ Classes based upon size and/or shape

Morphologi G4-ID - chemical measurement

› Automatically collect spectrum from centre of each selected particle

Morphologi G4-ID – chemical identification

› Automatically correlate particle spectra with library

Morphologi G4-ID - chemical correlation

› Measures strength of association between particle spectra and reference library spectra

› Correlation scores range from 0 – 1▪ 0 means no correlation▪ The correlation score is high for the active component and low for the excipient so based on

this the particle has been chemically identified as the active and this correlation score

information could be used further to create chemical classifications1 means strong

correlation

High correlation to Active

Low correlation to Excipient

Particle spectrum

Morphologi G4-ID - chemical classification

› Automatically classify using correlation scores

› Classify individual particles according to:▪ Highest score in library

› Can combine with morphological parameters▪ E.g. Size > 10um and score ingredient 3 >0.5

Morphologi G4-ID

Fully automated chemically specific particle sizing

Particle Size

Distribution of one

chemical entity

Unknown particles identified via external

database› Spectra can be exported directly to KnowItAll

▪ Search is automatically carried out

▪ Spectral corrections can be made

Application - identification of contaminants

› Presence of suspicious particles which may be contaminants in a dispersed sample ▪ e.g. particles with unexpected appearance

Contaminant particles in mixture

› Spherical particles identified within a powder› What are the spheres made of?

Collect spectra of suspicious particles

› Compare with user generated library or export to 3rd party format▪ Can choose text (*.csv) or industry standard *.spc

Morphologi G3-ID - Summary

› Integrates particle size, shape and chemical identity in one platform

› Fully automated Raman chemical classification of 1000s of particulates

› Simple SOP driven operation, from sample dispersion through to size, shape and chemical

analysis

› Suitable for dry powders, suspensions and membrane filters

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