Evaluating Antibody Stability with Nano Differential Scanning Calorimetry

Nicie Murphy | Morgan Ulrich
August 29, 2022

Antibody stability is crucial for antibody performance in therapeutics. High antibody thermostabilities are essential for creating products with a reasonable shelf life and avoiding problems with deterioration of the biophysical properties of the antibody.1
Many antibodies, in particular monoclonal antibodies, are very costly to produce.2 Many synthesis procedures may only produce a few milligrams when purifications are finished, which means characterizing and quality control checks on samples need to use minimal amounts. For some types of measurements, non-destructive approaches such as Raman spectroscopy may be appropriate, but this is not always suitable for evaluating antibody stability. Another alternative is nano differential scanning calorimetery (DSC), which is one of the best ways of measuring antibody stability with minimal sample preparation and consumption.

How can I measure antibody stability easily and with lower sample consumption?

Nano differential scanning calorimetry works by measuring temperature changes associated with antibody unfolding or denaturation events. Interpretation of the thermograms from nano DSC can provide information not just on whether the protein remains stable, but also on the types of denaturing involved from analysis of signal signs and peak shapes.

TA Instruments Nano DSC is an ultrasensitive nano differential scanning calorimetry instrument for reliable measurements of antibody and other macromolecule stability. Designed to be easy to use and capable of performing measurements with as little as 2 µg of sample, the Nano DSC is the ideal nano differential scanning calorimetry instrument for monitoring antibody stability for routine and research purposes.

What is Nano DSC, and how is it used to measure antibody stability?

Nano DSC is a kind of differential scanning calorimetry that measures the heat absorbed or released by dilute in-solution bio-molecules as they are heated or cooled. While differential scanning calorimetry has numerous applications across pharmaceuticals, electronics, composites, and more, the Nano DSC is specifically built to measure thermal changes in bio-molecules.

The TA Instruments Nano DSC is the industry-leading, highly-customizable nano differential scanning calorimetry instrument. This nano differential scanning calorimeter can be used to measure with great sensitivity antibody stability by performing temperature ramps on very small amounts of sample. By measuring the reaction heat loss or gain, the thermogram can identify any weaknesses in protein stability and be used for sample characterization.

Why is measuring antibody stability important?

Many biological species, including antibodies, have very strong structure-function relationships. Unwanted unfolding, where the intermolecular interactions between different regions of the antibody are disrupted, is one event that may lead to the degradation of the desired biophysical properties.1 Using nano differential scanning calorimetry to make such measurements can also be used to provide general structure information and investigate binding events, particularly for protein-ligand interactions.

Measuring antibody stability during the research and development phase of new therapeutic antibodies is very important as the stability is often one of the design parameters that needs to be considered as part of the research process.3

Why is Nano DSC the best option for measuring antibody stability?

Researchers choose the Nano DSC for a number of reasons. With Nano DSC you can achieve higher quality data with lower sample consumption than for other competitive designs. The unique capillary platinum cell design with 300 µL volume is designed for easy loading with ultimate reproducibility and sensitivity.

The Nano DSC offers the flexibility to design your own test, and a variety of accessories make the instrument perfectly tailored to your application and lab needs. One option is to include an autosampler that is compatible with up to two 96-well plates that can transform your nano differential scanning calorimeter into a ‘start and walk away’ machine. Programming options for wash sequences with exit ports for buffers and solvent solutions are available through the Nano DSC instrument operating software.

The Nano DSC autosampler is designed to enhance your productivity and throughput. Data can be imported directly into the NanoAnalyze software for model fitting and multi-batch file processing to accelerate the extraction of important parameters for your antibody stability analysis.

Contact TA Instruments today for an expert opinion on how nano differential scanning calorimetery will simplify your antibody stability analysis.


  1. Mcconnell, A. D., Zhang, X., Macomber, J. L., Chau, B., Sheffer, J. C., Rahmanian, S., Hare, E., Spasojevic, V., Horlick, R. A., King, D. J., & Bowers, P. M. (2014). A general approach to antibody thermostabilization. MAbs, 6(5), 1274–1282. http://dx.doi.org/10.4161/mabs.29680
  2. Samaranayake, Haritha, Thomas Wirth, Diana Schenkwein, Jani K. Räty, and Seppo Ylä-Herttuala. 2009. “Challenges in Monoclonal Antibody-Based Therapies.” Annals of Medicine 41(5):322–31. doi: 10.1080/07853890802698842
  3. Ma, Hui, Ciarán Ó’Fágáin, and Richard O’Kennedy. 2020. “Antibody Stability: A Key to Performance – Analysis, Influences and Improvement.” Biochimie 177:213–25. doi: 10.1016/j.biochi.2020.08.019.