Differential Scanning Calorimetry gives you more than a melting temperature: it turns thermal unfolding curves into clear decisions on candidate selection, formulation strategy, and comparability. Our team designs DSC studies around your specific biologics and questions, so every run delivers data you can actually act on.
Differential Scanning Calorimetry (DSC) is a core biophysical technique for assessing the thermal behavior of biomolecules. By monitoring heat flow as a sample is heated or cooled, DSC quantifies unfolding transitions, phase changes, and interactions that alter molecular stability.
For proteins, nucleic acids, lipids, and complex biologics, DSC provides direct insight into:
Because DSC measures heat capacity changes without labels or probes, it is widely used in biologics development, formulation optimization, and higher-order structure (HOS) characterization.
You can use DSC data to:
High-information thermal profiles- Capture unfolding transitions and domain behavior in a single, detailed curve.
Decision-ready thermodynamic metrics- Obtain Tm and ΔH values to compare candidates, lots, and formulations.
Label-free, formulation-relevant assays- Analyze native samples without dyes or tags, directly in relevant buffers.
Broad biomolecule coverage- Apply one DSC platform to proteins, antibodies, nucleic acids, lipids, and complexes.
Formulation and excipient screening- Rank buffers, pH conditions, and excipients based on measured thermal stability.
Built to complement other biophysical tools- Integrate DSC results with DSF, CD, ITC, SPR, or BLI in a single study design.
| Key Aspect | Differential Scanning Calorimetry (DSC) | Differential Scanning Fluorimetry (DSF) | Isothermal Titration Calorimetry (ITC) | Circular Dichroism (CD) | Surface Plasmon Resonance (SPR) |
| Core readout | Heat capacity change and unfolding transitions as temperature increases | Fluorescence change during thermal unfolding | Heat released or absorbed upon binding at constant temperature | Differential absorption of circularly polarized light | Change in refractive index at a sensor surface during binding |
| Best suited for | Global thermal stability, unfolding cooperativity, formulation and lot comparability | Rapid screening of stability trends across many variants or buffers | Binding thermodynamics, stoichiometry, enthalpy/entropy contributions | Secondary structure and overall fold; structural changes with conditions | Affinity and kinetics of surface-immobilized interactions, including small molecules |
| Labels / dyes | Label-free, native buffer compatible | Usually dye-based; some label-free options | Label-free | Label-free | Requires ligand immobilization on sensor chip; no fluorescent label |
| Typical throughput | Low to medium | Medium to high (plate-based) | Low | Medium | Medium to high (chip-based) |
| Typical questions | How stable is my protein or biologic? How do buffer, pH, excipients, or ligands shift Tm and unfolding enthalpy? | Which buffer or excipient gives higher apparent Tm? Which variants look more stable in a first screen? | Does my ligand bind? What are affinity and stoichiometry? What are the enthalpic vs entropic contributions? | Is my protein folded correctly? Does secondary structure change with temperature, pH, or buffer? | What are kon, koff, and KD? Are there kinetic or affinity differences between candidates or conditions? |
Project scoping and experimental design
We clarify your goals (stability ranking, comparability, binding or formulation screening), review sample information, and agree on scan range, heating rate, buffer system, and replicates.
Sample qualification and buffer preparation
Samples are checked for clarity, concentration, and buffer composition. If needed, we perform buffer exchange or matching to minimize baseline noise between sample and reference cells.
DSC run and instrument control
Samples and matching buffers are loaded into the DSC cells. Controlled heating (and, when appropriate, cooling) scans are run with instrument performance checks and blanks to confirm baseline stability.
Data processing and quality review
Raw thermograms are baseline-corrected and normalized. We extract key parameters such as Tm, onset temperature, and calorimetric enthalpy, and verify consistency across replicates and conditions.
Result interpretation and reporting
You receive a concise report with tables, overlaid curves, and a brief interpretation focused on your questions—for example, stability ranking, lot comparability, ligand effects, or formulation selection—plus recommendations for any useful follow-up assays.
Key features and specifications include:
Nano DSC (Fig from TA Instruments)
| Item | Requirement / Recommendation |
| Sample type | Purified proteins, antibodies, nucleic acids, or formulated biologics in clear, particle-free solution. Please avoid visible aggregates or phase separation. |
| Sample volume | Typically 300–500 µL per sample condition is recommended. If material is very limited, we can discuss a lower volume during project design. |
| Sample concentration | Moderate concentration suitable for stability studies. We will suggest a working range after reviewing your target and buffer information. |
| Buffer | Sample and reference should be in the same buffer. Please provide buffer composition and pH. |
| Excipients / additives | Common formulation excipients are generally acceptable. Please indicate any detergents, glycerol, DMSO, or other special components. |
| Storage | Store under your standard recommended conditions until shipment (e.g., refrigerated or frozen, as appropriate for the molecule). |
| Shipping | Ship cooled with cold packs unless otherwise agreed. Avoid repeated freeze–thaw cycles. |
| Labelling | Clearly label each vial with sample name or ID and concentration. |
| Documentation | Provide a sample list with IDs, buffer, concentration, and which samples you would like us to compare. |
Overlaid DSC thermograms for multiple formulations, with zoomed-in Tm shift and a Tm summary plot ranking samples by thermal stability.
DSC-derived stability summary showing Tm ranking, unfolding enthalpy (ΔH) for replicates, and a Tm heatmap across buffer conditions.
What types of projects benefit most from DSC?
DSC is most valuable when you need quantitative insight into thermal stability or unfolding behavior to compare candidates, formulations, or lots, rather than just a simple stability yes/no result.
Is DSC a destructive technique?
Yes, samples are heated through their transition range and are typically denatured after the run, so you should plan DSC as an end-point characterization step rather than expecting to recover material for further functional assays.
How do I choose between DSC and other biophysical methods?
Use DSC when your key question is “how does stability change with temperature or formulation”; use higher-throughput screening (such as fluorescence-based melting), structural spectroscopy (such as CD), or binding techniques (such as ITC, SPR, or BLI) when you primarily care about screening speed, secondary structure, or binding affinity and kinetics.
How much sample do I need for a DSC study?
In most cases you should plan for several hundred microliters per condition at a moderate concentration, and the exact volume and range can be fine-tuned during project design once we understand your molecule and goals.
Can DSC handle formulated biologics with excipients?
Yes, DSC can be run on real formulations as long as they are clear and well-behaved; very high levels of detergents, organic solvents, or unusual excipients may require minor adjustments, which we will discuss before the study starts.
Can DSC be used for biosimilar or lot-to-lot comparability?
DSC is commonly used to compare unfolding profiles and thermal parameters between reference materials, biosimilar candidates, and different manufacturing lots, helping you see whether samples behave similarly or if any show atypical transitions.
What information will I actually get from a DSC experiment?
You receive thermal curves and extracted parameters that show when the molecule starts to unfold, how cooperative that process is, and how strongly different candidates or formulations differ, so you can rank options and flag potential risks.
Can DSC support both early discovery and later-stage development?
Yes, DSC can help in early stages to filter out unstable constructs, in mid-stages to guide buffer and excipient selection, and later on to support comparability and process-change assessments as part of a broader characterization package.
Does DSC replace other stability assays?
No, DSC is best used as a thermodynamic backbone that complements other methods; combining DSC with orthogonal techniques gives a more complete view of stability, structure, and binding behavior.
What if I am not sure how to design the DSC study?
You only need to share your molecule type, current formulation or buffer, and main questions; the experimental setup—such as scan range, heating rate, and comparison groups—can then be tailored around those goals.
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