Differential Scanning Calorimeter

(DSC) and Recent Advances

By

Arikibe Joachim Emeka

PGChm University of the South Pacific

25th September, 2017.

What is Differential Scanning

Calorimeter (DSC)?

The term DSC refers to both the technique of measuring calorimetric data while scanning as well

as the specific instrument design.

A calorimeter measures the heat into or out of a sample

A differential calorimeter measures the heat of a sample relative to a reference

A differential scanning calorimeter does all the above and heats the sample with a linear

temperature range (Kodre et.al., 2016)

DSC measures the temperature and heat flows associated with transitions in materials as a

function of time and temperature in a controlled atmosphere.

These measurements provide quantitative and qualitative information about physical and

chemical changes that involve endothermic or exothermic processes or changes in heat

capacity(Wang et.al.,2017)

Principle of DSC

The DSC operates on the “null balance” principle.

The difference in heat flow to the sample and reference at the same temperature is recorded as a function of temperature. The reference is an inert material such as alumina or just an empty aluminum pan.

Fig 1. Schematic diagram of a conventional DSC (Kodre et.al., 2016)

Information obtainable from DSC

Glass transition temperature (Tg)

Melting point and boiling point

Crystallization time and temperature

Percentage crystallimetry

Heat of fusion and reactions

Heat capacity

Oxidative/thermal stability

Reaction kinetics

Purity

Rate and degree of cure

Fig 2. Typical features of a DSC trace (Polymorphic)

Endothermic events

melting

sublimation

solid-solid transitions

desolvation

chemical reactions

Exothermic events

crystallization

solid-solid transitions

decomposition

chemical reactions

baseline shifts

glass transition

Two types of DSC

Power Compensated DSC The temperature of the sample and reference material are always kept the same by varying the heat

flow to the sample and reference during linear temperature scanning process.

Fig 3. schematic diagram of heat compensated DSC (Kodre et.al., 2016)

Heat Flux DSC The temperature is directly recorded during the same procedure. Together

with the thermal resistance, the change in temperature can be converted to heat flow difference. In heat flux DSC, the total heat flow dH/dt can be written as,

dH/dt = Cpdt/dt+f(T,t)

Where, H = enthalpy in J mol-1

Cp=specific heat capacity in JK -1mol-1

f (T,t )= kinetic response of the sample in J mol-1

Fig 4. Schematic diagram of heat flux DSC (Kodre et.al., 2016)

Recent Advancements/Emerging Concepts in DSC

Microelectromechanical system Differential Scanning Calorimeter (MEMS-DSC)

The idea of MEMS-DSC was the result of two functional problems of conventional DSCs, that prevent them from performing effectively on biomolecular and structural transitions.

MEMS-DSC is polymer-based miniaturized DSC with integrated microfluids for analyzing structural transitions of biological molecules in liquid phase.

MEMS device consists of a pair of poly dimethyl siloxane (PDMS) calorimetric microchambers and fluid handling microchannel, with each chamber 1.2 µL in volume and based on a freestanding SU-8 diaphragm. A Ni-Cr thermopile, and Ni heaters and temperature sensors, integrated on the diaphragms to allow thermal measurements and control.

(Wang et al., 2008; Lin et al., 2017)

Fig 9.Design schematic of the MEMS DSC device (Wang et al., 2017)

MEMS DSC Continued

During DSC measurements, the chambers are filled with

biomolecular solution and reference buffer respectively.

As solution temperatures are varied continuously over a range of

interest, the biomolecular thermal powder is measured via the

thermopile output and then used to compute the thermodynamic

parameters of the biomolecule.

In a study by Wang et.al of the department of mechanical

engineering of Carnegie Mellon University, Pittsburgh, USA showed

how MEMS-based differential scanning calorimetry was employed for

determining the thermodynamic properties of biomolecules

Fig. 5. Device output as a function of temperature during unfolding of the proteins: (a) lysozyme and (b) RNase A. Fig. 6. Heat capacity difference as a function of temperature during unfolding of the proteins: (a)lysozyme and (b) RNase A

Fig. 7. Partial specific heat capacities of: (a) lysozyme and (b) RNase A during unfolding of the proteins Fig. 8. Enthalpy change and melting temperature for unfolding of the proteins: (a) lysozyme and (b) RNase A.

Hyphenated Techniques DSC-IR

DSC-IR has been used to look at the evolved solvents from pharmaceuticals

DSC-MS

DSC-MS has been used to look at the composition of meteorites and lunar rocks. It has also used for the determination of the purity of materials (polymers, inorganic compounds, pharmaceutical products, etc).

DSC-FTIR

DSC has also been coupled to FT-IR microscopy to look at changes in a sample during a DSC run.

Lin et.al employed the hyphenated technique of DSC-FTIR microspectroscopy to the behavior of theophylline-citric acid co-crystals at Yuanpei University, Taiwan.

DSC-Raman

DSC-Raman is a technique where a sample is irradiated by a Raman laser as the sample is run in DSC profile. Because of the nature of the Raman spectrometer, it is ideally suited for this as it does not require any processing of neither reflectance spectra nor the use of a special transmission path cell.

DSC-Raman shows great potential for the study of polymorphic materials, polymeric-crystallization, and chain movements at the glass transition, and for hydrogen bonding polymers.

(www.PerkinElmer.com, Bhusnure, 2015)

Fig. 11.HINSEIS HDSCPT 1600 Fig12. Schematic diagram of hyphenated DSC technique

(http://www.tainst.com. )

Hyphenated Techniques continued

Ultraviolet Differential Scanning Calorimeter (UV-DSC)

UV-DSC also known as photo DSC is a DSC that has been adapted to allow the sample to

be exposed to UV-light during the run.

This can be done with several types of light sources including Hg vapour lamps or LEDs

over a range of frequencies and intensities.

UV-DSC has been used to study UV initiated curing systems in the DSC, such as those used

for dental resins, orthopedic bone cements, hydrogels, paints or coatings and adhesives.

It has been used to study the efficiency of curing and to develop kinetic models for curing

systems.

Used to study decomposition of materials under UV radiation. Thus, can be used for

understanding the effect on the storage of pharmaceuticals on antioxidant packages in

polymers and rubbers, on food properties or on dyes in sunlight (www.PerkinElmer.com;

wang et.al, 2017)

Fig 13. PerkinElmer DSC 6000 with UV-Photocalorimeter accessories (www.perkinelmer.com)

Temperature Modulated Differential Scanning Calorimeter (TMDSC) or Alternative

Current Differential Scanning Calorimeter (ACDSC)

The basic idea of the TMDSC is to add a controlled temperature modulation to the conventional linear

heating.

The heating process of TMDSC can be divided into two parts.

The first part is to heat the sample at a certain temperature scanning rate just like the conventional

DSC.

In the second part, the heat capacity component of the heat flow is obtained by applying a controlled

oscillating temperature modulation with a zero net temperature change.

In a TMDSC thermal analysis, the average scanning rate, the period of modulation and the temperature

amplitude of modulation are three important variables that are tuned to optimize the experiment

Virtually all biological phenomena depend on molecular interaction. A basic biology problem is to

understand the folding and denaturation processes of a protein, i.e., the kinetics and thermodynamics

of how a protein unfolds and folds back into its native state

Both folding/unfolding and denaturation processes are associated with enthalpy changes. The

intermolecular interactions such as protein-ligand association, protein/DNA interaction antigen-

antibody binding processes are either enthalpically or entropically driven, depending upon the binding

modes of the small molecules (Mooter et al., 2016; Knoop et al., 2010)

fig 14.MTDSC heating profile Fig 15. PerkinElmer DSC 8500 (MTDSC)

the underlying heating rate is 1°C/minute, the modulation period is 30 seconds, and the modulation amplitude is ±1°C. This set of conditions results in a sinusoidal heating profile where the instantaneous heating rate varies between +13.44°C/minute and -11.54°C/minute (i.e., cooling occurs during a portion of the modulation

As in conventional DSC, MDSC can also be run in a cooling rather than heating mode.

MDSC is a valuable extension of conventional DSC. Its applicability is recognized for precise determination of the temperature of glass transition and for the study of the energy of relaxation. It has been applied for the determination of glass transition of Hydroxypropylmethylcellulose films and for the study of amorphous lactose as well as some glassy drugs.

TMDSC continued

MTDSC was used to study to assess the purification yield of some pharmaceutical

antibiotic drugs in a study conducted by Knoop et.al published in the European

Journal of Pharmaceutical Sciences.

Fengwei et.al of Centre for High Performance Polymers, Australian Institute for

Bioengineering and Nanotechnology, The University of Queensland, Brisbane,

Australia also used MTDSC to study the thermal transition of starch.

Mooter et.al of the Laboratory for Pharmacotechnology and Biopharmacology,

Campus Gasthuisberg, Belgium, used MTDSC to study the armophous

crystallization of ketoconazole.

Meuter et.al studied the thermal transitions of maltriose, maltohexose and TPS

by measuring the heat capacity in the quasi-isotherma mode.

TMDSC has also found relevance and utilizded in various researches in food

sciences.

Fast Scan DSC (FSDSC) or HyperDSC FSDSC or HyperDSC is a technique that apply very high heating

rates to a sample to increase the sensitivity of a DSC or to trap

kinetic behavior.

Fast scan heating rates range from 100oC /min - 300 oC /min where

HyperDSC heating rates range from 300 oC /min - 750 oC /min.

When heating rates of 100 oC /min - 750 oC /min are applied, the

response of the DSC to weak transitions is enhanced. It is then

possible to see very low levels of amorphous materials in

pharmaceuticals, measure small amounts of material products,

freeze the curing of thermosetting compounds, inhibit the cool

crystallization of polymers as well as thermal degradation of

organic materials (Wang et al., 2017)

Self-Reference DSC (SR-DSC)

The idea of SR-DSC was formed because of one disadvantage of power compensation systems. The problem was their effectiveness over temperature range 170 -730oC, hence the development of higher temperature DSC

SR-DSC technique as a heat flux DSC was applied in which difference in heat flow rate between the sample and the furnace is monitored against time or temperature, and the sample is subjected to a temperature programme.

SR-DSC has a single position in its center to place a sample but has no place for reference. This absence avoids any baseline inconsistency as a result of device asymmetry and also it nullifies any thermal noise at interface of the reference plate.

Gas Flow Modulated DSC (GFMDSC)

Modulates a DSC by setting the properties of a gas in thermal contact with the sample and the reference in the calorimeter. The device allows the use of MDSC at high modulation rates as compared with the modulation rates use MTDSC.

The major heat-flow between sample or reference and the future is the purge gas in the furnace chamber. The composition of purge gas in the furnace chamber is of a DSC cell as modulated by alternatively purge gas in the DSC

Parallel-Nano-DSC (PNDSC)

Is a power compensation DSC that includes a plurality of cell structure, being used to define a selective region for calorimetric measurements of a nanomaterial.

It combines DSC and combinatorial analysis in a novel way, which is ideal for analyzing complex material systems.

Shimadzu DSC 60TA DSC

HINSEIS HDSCPT 1600 PelkinElmer DSC 8500

PelkinElmer DSC 6000

(a)The MicroCal VP-DSC (b) the TA DSC

Different DSCs on Display

ReferencesM.M. Knoop, K. Lobmann, D.P. Elder, T. Rades, R. Holms, Recent advances and potential applications of Modulated Temperature Differential Scanning Calorimeter in drug development. European Journal of Pharmaceutical Sciences 87 (2016) 164-173

S. Yu, S.Wang, W. Lu, L. Zuo, Review of MEMS differential scanning calorimetry for biomolecular study, Front. Mech. Eng. (2017) 1-13

H.L. Lin, P.C. Hsu, S.Y. Lin, Theophylline-citric acid co-crystals easily induced by DSC-FTIR microspectroscopy or different storage conditions, Asian Journal of Pharmaceutical Sciences 8 (2013) 19-27.

G.V. D. Mooter, D.Q.M. Craig, P.G. Royall, Characterization of amorphous ketoconazole using modulated temperature differential scanning calorimeter, International Journal of Pharmaceutical Sciences 90 (2001) 996-1003

F. Xie, W. Chun Kui, P. Lui, J.Wang, P.J. Hally, L. Yu, Starch thermal transitions comparatively studied by DSC and MTDSC, Starch 62 (2010) 350-357

K.V. Kodre, S.R. Attarde, P.R. Yendhe, R.Y. Patil, V.U. Barge VU, Differential Scanning Calorimetry: A Review, Research and Reviews: Journal of Pharmaceutical Analysis 3 (2014) 11-22

L. Wang, B. Wang, Q. Lin, Demonstration of MEMS-based differential scanning calorimetry for determining the thermodynamic properties of biomolecules, Sensors and Actuators B: Chemical 134 (2008) 953 – 958

O.G. Bhusnure, Solid sample differential scanning calorimetry in biopharmacutical discovery and development, World Journal of Pharmaceutical Sciences 5 (2015) 440-454

Linseis Thermal Analysi available at www.linseis .com

Thermal Analysis Instruments 60 series, Shimadzu corporation. Available at www.shimadzu.com/an/

R.L. Danley, P. A. Caulfield, DSC Baseline Improvements Obtained by a New Heat Flow Measurement

Technique, TA Instruments. Available at http://www.tainst.com.

Differential scanning calorimeter, Beginner’s gude. Available at www.perkinelmer.com

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