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Archimedes is a new, highly innovative instrument which uses the technique of resonant mass measurement to detect and accurately count particles in the size range 50nm - 5µm, and reliably measure their buoyant mass, dry mass and size. Particularly useful for the characterization of protein aggregates in formulation or buffer, Archimedes is also able to distinguish between proteinaceous material and contaminants such as silicone oil by means of comparing their relative resonant frequencies and buoyant masses.

Overview

Archimedes is an innovative, high-performance system which harnesses the technique of resonant mass measurement in order to detect and count particles in the size range 50nm - 5µm and to measure particle mass and size. Archimedes is uniquely positioned to quantitatively measure protein aggregates within and beyond the range of 200nm - 5µm, highlighted as a particular concern for immunogenicity and product safety.

Central to Archimedes is a MEMS (Micro Electro-Mechanical Systems) technology sensor, allowing the highly sensitive, reliable and reproducible measurement of aggregates, one by one. Archimedes is also capable of providing information on sample concentration, viscosity, polydispersity, density and volume, and distinguishing between negatively buoyant proteinaceous particles and positively buoyant contaminating silicone oil droplets.

Parameters measured:

  • Particle number.
  • Particle size.
  • Particle buoyant mass.
  • Particle dry mass.
  • Particle density.
  • Particle surface area.
  • Sample volume.
  • Sample concentration (particles/mL).
  • Sample density.

Key Benefits:

  • Ideally positioned for biopharmaceutical manufacturers and developers.
  • Unique and accurate particle counting capability in the size range 50nm - 5µm.
  • Exquisite sensitivity: measurement of particle mass to 350ag.
  • Highly accurate particle size measurement from 50nm to 5µm.
  • Excellent size resolution, <20nm at 1µm diameter.
  • Low sample consumption: only 100µL.
  • Differentiation between negatively buoyant and positively buoyant particles.
  • Capable of measuring high concentration samples (to 109 particles/mL) and high viscosity samples (to 100cP).
  • Fast, NIST-traceable calibration.
  • Highly reproducible results.
  • Intuitive and flexible ParticleLab software.

How it works

Archimedes uses the technique of resonant mass measurement to count and characterize particles. At the heart of Archimedes is a MEMS (micro electro-mechanical systems) sensor. Two types of sensor: the Micro sensor and the Nano sensor, are available for various applications. Each sensor comprises a microfluidics network and a minute cantilever which resonates with a particular frequency. Embedded in this cantilever is a microfluidic channel. As the advanced fluidics system of Archimedes pushes sample through this channel, the resonant frequency of the cantilever alters. This shift in the frequency of resonance is measured by a laser, focused on the tip of the cantilever, which is then transmitted to a split photodiode detector.

Each particle which passes through the sensor causes a change in the resonant frequency, giving an accurate and precise measurement of the particle’s buoyant mass – whether positive or negative - in the sample. From this measurement, the mass, size (equivalent sphere), and surface area of the particle are calculated. Overall measurements are also made of sample concentration, density, volume, and polydispersity.

Accompanying Archimedes is ParticleLab software, offering flexibility and versatility in both instrument control and data manipulation and presentation. ParticleLab is straightforward and intuitive, enabling precise instrument control and adjustment and a range of data handling capabilities.

Specification

Archimedes is able to measure a wide range of parameters simply and quickly, following the principles of resonant mass measurement.

Measurement type 1: Particle Size

Measurement range:
50nm* - 5µm.
Accuracy:
Better than +/- 1% on NIST traceable latex standards.
Precision / Repeatability:
Better than +/- 1% on NIST traceable latex standards.
Resolution:
Better than +/- 20nm at 1µm, polystyrene beads in H2O.

Measurement type 2: Particle Buoyant Mass

Lower Limit of Detection:
350ag.
Accuracy:
Better than +/- 3% on NIST traceable latex standards.
Precision / Repeatability:
Better than +/- 3% on NIST-traceable latex standards.

Measurement type 3: Particle Counting/Sample Concentration

Measurement range:
104 particles/mL – 109 particles/mL.
Accuracy:
Better than +/- 10% on NIST traceable latex standards.
Precision / Repeatability:
Better than +/- 5% on NIST traceable latex standards.

Measurement principle: Resonant Mass Measurement.

Drawn sample volume:
100µL.
Measured Sample Volume Range:
10nL - 10µL.
Sample Viscosity Range:
<1cP -100cP
Accuracy in Fluid Density:
<0.002g/cc for densities in range 0.8g/cc – 1.2g/cc.
Patents:
US 8087284 B2.
Light source:
685nm, 35mW laser.

Weight and dimensions

Dimensions (W, D, H):
610mm x 585mm x 305mm.
Weight:
23.6kg.
Power:
110V or 220V.

Operating environment

Temperature:
18°C – 25°C.
Humidity:
35% - 80% non-condensing.
*:
Sample dependent

Accessories

Archimedes

Calibration standards NIST-traceable monodisperse calibration standards for Micro and Nano sensors Image Two types of NIST-traceable standards, one each for Hi-Q Micro and Nano sensors used in Archimedes. More information
Sensors The heart of Archimedes Image MEMS (Micro Electro-Mechanical Systems) sensors provide the central functionality of Archimedes, enabling resonant mass measurement of particles. More information
Vials and seals Two types of screw-top glass vial – 20mL and 40mL capacity - are available for use with Archimedes. By using the dedicated vial seals a snug fit to the instrument is created, enabling pressure to be maintained throughout Archimedes’ fluidics system. 20mL and 40mL screw-top glass vials. Vial seals create a pressure-tight fitting. Vials need only be finger-tight. Additional seals available for snug fitting of fluidics lines into reference and waste bottles. Inserts such as eppendorf tubes may be used for smaller sample volumes inside 20mL vial. Sample may be drawn directly from a syringe placed inside 40mL vial.
Reference fluid and Detergent Both deuterated water and a detergent solution are provided for use with Archimedes. Deuterated water provides a fluid density gradient inside Archimedes’ fluidics system, and should be pre-mixed with deionized water for optimal operation of the system. Detergent is designed for use when Archimedes is measuring protein solutions and will clean both sensors and the internal fluidics network of the instrument. Pre-prepared, long-lasting detergent acts within seconds to remove stubborn aggregates and debris. Deuterated water is used in small volumes to provide a density gradient in Archimedes and keep sample flow moving in the required direction. Simple and intuitive use with Archimedes.

Support

When you purchase a Malvern product we understand that this is just the first stage of a working relationship that will last for the lifetime of the instrument. Some customers just need to ask an occasional question or to download a software upgrade, whilst others require a comprehensive support contract with priority call out and fixed cost of ownership. Whatever your situation Malvern will provide the right support for you.

Help Desk

  • Telephone and email support.
  • Operators who take responsibility for your call and ensure your query is answered. 

Training

  • On Site training courses
  • Classroom training
  • E-learning

Resource center

  • Application notes
  • Technical notes
  • On demand presentations
  • Live webinars

Software downloads

  • A simple mechanism for receiving updates and new features

Platinum and Gold Service Contracts

  • Protection from the cost of downtime
  • No time lost in obtaining help when you need it
  • Fixed cost of ownership

Bronze Service Agreements

  • Protect the value of your investment
  • Reduce the risk of downtime
  • Protect the validity of your data
 
 

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Use of Resonant Mass Measurement in biopharmaceutical development Article (English)

Resonant Mass Measurement technology covers a key size range of 200nm to 5µm for protein aggregation measurement. It requires less than 100µL of sample to give quantitative information on aggregate mass and count


Keywords: English Article Particle size Sub-visible particles Resonant mass measurement Protein aggregation Proteins Biological drug characterization and development Bio-formulation development Biopharmaceutical manufacturing Archimedes 

Introducing Archimedes, Particle Metrology system Webinar - Recorded (English)

An introduction to Archimedes, the technique of resonant mass measurement, and how this technology is vital in understanding and monitoring early aggregation events in your biopharmaceutical formulation

Product:
Archimedes
Date recorded:
February 18 2013
Language:
English

Keywords: English Webinar - Recorded Greenwich Time Resonant mass measurement Protein aggregation Archimedes 

'Critical to Quality' measurements of protein aggregation in biopharmaceuticals Article (English)

Developing stable formulations of proteins is crucial to successful drug delivery, efficacy and lack of immunogenicity. SEC, DLS and Resonant Mass Measurement techniques provide valuable insight into a proteins behaviour in formulation


Keywords: English Article Molecular size Molecular weight Dynamic Light Scattering Size Exclusion Chromatography Zetasizer Nano range Resonant mass measurement Protein aggregation Proteins Archimedes Viscotek systems 

Characterizing Biopharmaceutical Formulations using Archimedes Technical Note (English)

Archimedes is an innovative new benchtop instrument which detects and counts individual protein aggregates and other particles, and measures their mass and size down to 50µm by means of resonant mass measurement


Keywords: English Technical Note Molecular size Particle size Resonant mass measurement Proteins Antibodies and derivatives Archimedes 

Pharmaceutical companies have fewer resources from which increased productivity is required Article (English)

Discovering and developing drugs is becoming a progressively expensive and high-risk venture. Consequently, productivity must increase at all stages of the pharma production process, from drug discovery though to manufacturing.


Keywords: English Article Mastersizer range Morphologi G3 Pharmaceutical development Drug discovery Pharmaceutical formulation and development Archimedes 
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