The Morphologi 4-ID offers an exclusive capability, combining all the benefits of automated static imaging delivered by the Morphologi 4 with chemical identification of individual particles by Raman spectroscopy in a single measurement.

  • Patented MDRS capability delivers representative component-specific particle size and shape data, delivering full characterization of your sample
  • All the functionality of the Morphologi 4 combined with a dedicated Raman platform for both physical and chemical particle characterization in a single, automated measurement
  • Automatically measures Raman spectra for hundreds or thousands of particles, saving valuable analyst time
  • Intuitive software ensures suitability for experienced and non-experienced spectroscopists alike
  • Easy correlation of morphological properties with chemical information provides the most comprehensive understanding of your sample
  • 21 CFR Part 11 software option ensures regulatory compliance
  • Adaptable workflows enable methods to be tailored to specific user or application requirements. Select particles for chemical analysis:
    • manually, from particle images
    • morphologically-directed, based on user-specified classifications (MDRS)
    • automatically and objectively by the software
  • Ability to export spectra in industry-standard format supports unknown component identification using 3rd party spectral libraries
  • Tight control of laser power and acquisition time enables measurement optimization for a wide range of materials, from weak Raman scatterers to those that are thermally sensitive


The Morphologi 4-ID measurement procedure can be split into five sections: 

Sample preparation  
Spatial separation of individual particles and agglomerates is critical to robust results.  The integrated dry powder disperser makes preparing dry powder samples easy and reproducible. The applied dispersion energy can be precisely controlled, enabling the measurement process to be optimized for a range of material types.  Accessories that fit directly in to the Morphologi 4-ID’s automated stage are available for preparing suspended or filtered samples. 

Image capture 
The instrument captures images of individual particles by scanning the sample underneath the microscope optics. The Morphologi 4-ID can illuminate the sample from below or above, whilst accurately controlling the light levels. 

Image processing 
Use of either the automated ‘Sharp Edge’ segmentation analysis or the manually-controlled thresholding enables the detection of particles and the calculation of a range of morphological parameters for each.

MDRS 
Components and particles of interest are targeted for Raman analysis.  Particles can be selectively targeted based on their morphology, or particles representative of the whole sample can be targeted objectively by the Morphologi software.

Result generation 
Advanced graphing and data classification options in the software ensure that extracting the relevant data from the measurement is straightforward, via an intuitive visual interface.  Correlation scores to a reference library are calculated for each Raman spectrum acquired, enabling particles to be classified based on their chemistry.  The morphological data associated with the particles in each chemical class is used to generate size and shape distributions, delivering component-specific morphological information.  Individually-stored grayscale images for each particle are linked to their Raman spectra and provide qualitative verification of the quantitative results.

General:

Technology:
Static automated imaging
Particle size:
0.5 μm – 1300 μm (upper limit may be extended for some applications*)
Particle properties measured:
Size, shape, transparency, count, location
Particle size parameters:
Circle equivalent (CE) diameter, length, width, perimeter, area, maximum distance, sphere equivalent (SE) volume, fiber total length, fiber width
Particle shape parameters:
Aspect ratio, circularity, convexity, elongation, high sensitivity (HS) circularity, solidity, fiber elongation, fiber straightness 
Particle transparency parameters:
Intensity mean, intensity standard deviation
Integrated Sample Dispersion Unit:
For fully automated dispersion and measurement of dry powders. Manual or SOP control of
dispersion pressure, injection time and settling time
Illumination:
White light LED: brightfield, diascopic and episcopic; darkfield, episcopic
Detector:
18 MP; 4912 x 3684 pixel color CMOS array; pixel size 1.25 μm x 1.25 μm
Optical system:
Nikon CFI 60 brightfield / darkfield system
Lens (and particle size range):
2.5x: 8.5 µm – 1300 µm (nominal) 
5x: 4.5 µm – 520 µm (nominal) 
10x: 2.5 µm – 260 µm (nominal) 
20x: 1.5 µm – 130 µm (nominal) 
50x: 0.5 µm – 50 µm (nominal)

Raman Spectroscopy:

Size range:
1 μm - 1300 μm*
Spectral performance:

150 cm-1 to 2800 cm-1
6 cm-1 resolution measured on an atomic line source. Average of < 8 cm-1 across the range.

Wavelength:
785 nm
Power output from spectrometer:
< 100 mW
Power output at sample:
> 45 mW at max power
Laser spot size:
2 µm at 50x magnification
Laser safety:
Class 1
Chemical identification method:
Raman spectral correlation

Weight and dimensions:

Dimensions (W, D, H):
810 mm (W) x 520 mm (D) x 685 mm (H)
with carry handles: 1100mm (W) x 520mm (D) x 685mm (H)
Weight:
80 kg (88 kg including carry handles)
Power:
100-240 V ac 50/60 Hz (<100W load)
Notes:
* Sample and substrate dependent

Appropriate dispersion of the individual particles and agglomerates within a sample leads to robust and reliable results. Good spatial separation and representative sampling of the particles is required.  To achieve this, a number of dispersion options are available with the Morphologi 4-ID.

Easy, reproducible, automated sample dispersion 
Morphologi 4-ID comes with an integrated dry powder dispersion unit.  It enables simple, reproducible preparation of dry powder samples.  A precise amount of sample is dispersed automatically using a unique compressed air dispersion mechanism controlled from within the software, for reproducible dispersions every time. 

Optional accessories – for analysis of particles in suspension 
A range of instrument accessories supports preparation of samples on microscope slides, in wet suspensions or on filters, extending the capability of the Morphologi 4-ID beyond the characterization of dry sample dispersions.  Each accessory fits directly into the automated stage area and is easily selectable in the Morphologi software.

2-Slide and 4-Slide holders 
‘Sandwiching’ a few μL of a particulate suspension between a microscope slide and a cover slip is a traditional method of sample preparation for microscopy.  Samples are presented in this form using either the 2-slide or 4-slide holder.  The 4-slide holder is supplied with each instrument, and the 2-slide holder can be purchased as an optional extra. 

Thin-path wet cell 
The thin-path wet cell is designed for both morphological and chemical characterization of up to 100 μL of sample.  It is ideal for applications such as the identification of subvisible particles in therapeutics (described by guidance in USP <787> and USP <788>), especially when a traditional membrane filtering approach may compromise particles of interest, such as protein aggregates.

25 mm and 47 mm diameter filter holders 
Methods used to detect and characterize particles in suspension often rely on capturing the particles on a membrane filter. Dedicated filter holders (25 mm or 47 mm diameter) and also the 2-slide holder allow samples on filter membranes to be presented directly to the instrument for analysis.

Fused silica filters and holder 
Fused silica filters are designed to enable the analysis of filtered samples containing low-contrast particles, such as protein aggregates or contaminant particles.  The fused silica filters are housed in a support for ease of handling, and are presented to the Morphologi in the fused silica holder, which can hold up to 2 filters.

Morphologi 4-ID provides value in a wide range of applications, some of which are described below:

Building materials 
Cement is a complex mixture of minerals and additives, the component-specific particle properties of which affect final product performance.  The capability of the Morphologi 4-ID system to analyze and characterize specific particle populations within a cement blend enables different batches or products to be compared, aiding product development and solving production problems.  It brings new insight to conventional cement manufacture and supports industry objectives to incorporate environmentally sustainable replacement materials, such as fly ash and blast furnace slag.

Energy storage/batteries  
Morphologi ID systems can support product development and ensure final product quality by providing information on the chemical composition and structure of electrode materials, enabling their correlation with battery performance.

Forensics
Forensic analysis requires physical and chemical information to interpret evidence.  Raman spectroscopy is routinely used in forensic investigations and combining this with automated imaging provides enhanced insight into the physical and chemical properties of unknown and complex mixtures, allowing differentiation between morphologically similar substances.  The particle size, shape and chemical information delivered by Morphologi systems enables the detection of counterfeit pharmaceuticals or illicit drugs, the identification of contaminant particles in powders, and the examination of soils and other residues from crime scenes to support the investigative process. 

Mining and minerals 
The morphology of geological deposits helps trace the extent of natural disasters and predict the impact of future environmental events. Particle properties also determine the effectiveness of abrasive minerals for use in cutting and polishing tools. Morphologi automatically generates the statistically relevant, component-specific particle data required to meet these challenges.

Pharmaceutical development 
Morphologi ID systems are used by companies across various stages of the pharmaceutical development cycle. The rapid, chemical component-specific morphological information helps to optimize and control both API and excipient particle size and shape during development, and throughout formulation and processing.  For generics, this information can be used to simplify and solve deformulation challenges and help establish in vitro bioequivalence. It can also be used to detect anomalies, contaminants and pinpoint process deviations during manufacturing.