Differential Scanning Calorimetry (DSC) is a powerful analytical tool for characterizing the thermal stability of proteins and other biomolecules. The technique measures the enthalpy (ΔH) and temperature (Tm) of thermally-induced structural transitions of molecules in solution. This information provides valuable insights into factors that stabilize or destabilize proteins, nucleic acids, micellar complexes and other macromolecular systems. The data are used to predict shelf-life of biomolecular products including biopharmaceuticals to enable batch-to-batch and biosimilar versus innovator molecule comparisons, to develop purification strategies, to characterize and evaluate protein constructs, and to rank the affinities of ligands to their protein targets in small molecule drug discovery programs.

The high-throughput, high-sensitivity MicroCal PEAQ-DSC Automated system features software that streamlines workflows through simplified experimental setup and flexible instrument scheduling. Automated data analysis supports the generation of high integrity thermal stability data and delivers compliance with regulatory requirements, whilst allowing easy integration into existing data handling and transfer systems.

Key Features

  • Gold standard stability-indicating technique requiring minimal assay development 
  • Direct and label-free measurement of biomolecular native-state stability in solution 
  • Standard 96-well plate format for high capacity and easy loading, with thermostatically-controlled storage of up to 6 plates
  • Fully integrated autosampler enables unattended analysis of up to 50 samples per day
  • Automated cell filling and cell cleaning functions permit unattended operation 
  • Measurement of very tight binding constants, up to 1020M-1
  • Powerful MicroCal PEAQ-DSC software minimizes typical data analysis time and includes:
    • PEAQ-Compliance: The system is available with Malvern Access Controller (MAC) to limit access to user-defined SOPs and data analysis features. Data can be displayed using the Report Generator with user details and the ability to sign using electronic signatures to facilitate the integration of the workflow into your company’s quality system and aid compliance with 21 CFR Part 11 and Annex 11 regulations. This is provided as an optional accessory
    • PEAQ-Performance: Automatically detects and validates system readiness for optimal performance
    • PEAQ-Smart (including PEAQ-Finder): For SOP-based operation and data analysis.  Provides new algorithms to detect even subtle peaks and shoulders, facilitating the automatic, non-subjective identification of multiple transitions, such as those seen in multi-domain proteins
    • PEAQ-Compare: For the quantitative comparison of DSC traces for comparability studies, ideal for batch-to-batch and biosimilarity studies
    • Network-ready: email updates sent during the analysis to keep you informed of assay progress

The MicroCal PEAQ-DSC is also available as a manual system without the autosampler.

Functional structures formed by proteins and other macromolecules often undergo temperature-induced conformational changes, such as unfolding. These changes result in the absorption of heat as a result of the redistribution of non-covalent bonds within the molecule. Differential Scanning Calorimeters measure this heat uptake very precisely.

The thermal core of the MicroCal PEAQ-DSC Automated system contains a sample cell (containing the sample of interest) and a reference cell (containing a matched buffer solution), both of which are housed within an insulating jacket. These two cells are always maintained at the same temperature, and during a measurement, they are heated at a constant scan rate. 

As the molecule within the sample cell unfolds, heat is absorbed, creating a temperature difference (ΔT) between the sample cell and the reference cell. This results in a thermal gradient across the Peltier units, creating a proportional voltage, which is in turn converted to power to form a feedback loop to the Peltier units, in order to return ΔT to zero.

Since protein unfolding is an endothermic event, it is observed as a positive displacement in the thermogram. The midpoint of this protein ‘melting’ transition is the Tm, and the area under the curve is the enthalpy (ΔH) of the unfolding process (please see figure below).


Data analysis and measured/derived parameters are described in greater detail on the Differential Scanning Calorimetry technology page.

General

Technology:
Differential Scanning Calorimetry
Measurement type:
Temperature midpoint (TM)
Enthalpy (ΔH)
Heat capacity change (ΔCp)

Cell

Cell:
Capillary
Cell material:
Tantalum
Cell volume:
130 μL

Sample

Sample capacity:
288 (6 × 96-well plates)
Sample volume:
325 µL
Typical sample concentration:
0.01 mg/mL – 10 mg/mL 1
Sample throughput:
≤50 samples/day
Sample storage temperature range:
4°C - 40°C

System

Noise:
0.05 μCal/°C 2
Baseline repeatability:
1 μCal/°C 2
Response time:
5s 2
Repeatability:
<0.2 µCal/°C 3
Reproducibility:
<0.08°C St. Dev. TM and <2% RSD on ΔH 4
System reproducibility:
<0.1°C St. Dev. TM and <5% RSD on ΔH 4
Multiple feedback modes:
Yes (passive, high gain and low gain)
Temperature range:
2°C to 130°C 2, 5
Maximum scan rate:
240°C/h
Reverse scanning:
Yes
Pressure perturbation calorimetry (PPC):
N/A
Cleaning routines:
3 pre-programmed routines
Cleaning solvents:
Water and detergent used as standard

Software

21 CFR part 11:
Yes, with PEAQ-Compliance software option
Network ready:
Yes, with email alert capability

Operating environment

Operating temperature (°C):
+10°C to +28°C
Storage temperature:
-20°C to +50°C
Humidity:
10% to 70%, non-condensing (10% to 90% for storage)
Ingress Protection (IP) rating:
IP21
Power:
100-240 V A/C, 50/60 Hz, 70 W (cell), 400 W (max, autosampler), PC as supplied
Certification:
CE (EN61010-1), EMC (EN61326-2-1, EN61326-1, FCC, ICES, VCCI), ISO9001:2008

Weight and dimensions

Dimensions (W, D, H):
101 cm × 68 cm × 70 cm
Weight:
Approx. 25 kg

Notes

:

1 Sample dependent

Typical results for ribonuclease (RNase) in 50 mM KAc buffer at pH 5.5, at 60°C/h with high feedback

3 Rescans of a stable buffer

4 Using ribonuclease (RNase)

5 Range may be extended down to -10°C upon request

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