Microcalorimeter application

Modern heat flow microcalorimeters employ a diversity of heat sinks and cells, depending on the applications for which they were designed. The heat sinks can be water baths, kept at a constant temperature ( 5 x 10-4 K) and typically operating in the range of 20-80 °C, or metal blocks, allowing much wider temperature ranges (e.g., -196°C to 200°C, 20°C to 1000°C). In some cases it is possible to scan the temperature at a predetermined rate (see chapter 12). 

A micrograph of the single-ended hotplate-based microsystem is shown in Fig. 6.2 and features a die size of 5.0 x 2.9 mm. This system is a minimal implementation of a temperature-controlled microhotplate system. Temperature modulation is facilitated by an direct access to the input voltage A modulation of the input voltage is translated into a modulation of the microhotplate temperature. Another interesting application of the system includes its use as a microcalorimeter or as a material research platform [145]. The schematic of the temperature-control loop is shown in Fig. 6.3. 

An apparatus with high sensitivity is the heat-flow microcalorimeter originally developed by Calvet and Prat [139] based on the design of Tian [140]. Several Tian-Calvet type microcalorimeters have been designed [141-144]. In the Calvet microcalorimeter, heat flow is measured between the system and the heat block itself. The principles and theory of heat-flow microcalorimetry, the analysis of calorimetric data, as well as the merits and limitations of the various applications of adsorption calorimetry to the study of heterogeneous catalysis have been discussed in several reviews [61,118,134,135,141,145]. The Tian-Calvet type calorimeters are preferred because they have been shown to be reliable, can be used with a wide variety of solids, can follow both slow and fast processes, and can be operated over a reasonably broad temperature range [118,135]. The apparatus is composed by an experimental vessel, where the system is located, which is contained into a calorimetric block (Figure 13.3 [146]). 

Application of calorimetric method to determine the rate of template polymerization was elaborated by Smid. The method is based on heat determination in microcalorimeter, followed by determination of the heat of blank polymerization as well as the heat of complexation. 

The essential requirements for the application of this direct method are a sensitive microcalorimeter (preferably of the heat-flow type, as described in Section 3.2.2) combined with equipment for the determination of the amount adsorbed. Although the assemblage of the apparatus is somewhat demanding, once the effort has been made the advantages of calorimetry are as follows ... 

The most common applications of calorimetry in the pharmaceutical sciences are formd in the subfields of differential scanning calorimetry (DSC) and microcalorimetry. State-of-the-art DSC instruments and microcalorimeters are extremely sensitive and are powerful analytical tools for the pharmaceutical scientist. 

As has been shown in this chapter, the differential scanning calorimeter and microcalorimeters have been shown to have wide applications in all aspects of pharmaceutical sciences, such as in preformulation and formulation development. However, the utility of these instruments is only possible with careful attention to following established calibration procedures. The DSC and other calorimeters are a critical part of a pharmaceutical scientists armamentarium. 

Despite the great diversity in the design of microcalorimeters and the experimental procedures described in the literature [1-10], only two microcalorimetric methods have found widespread application in cydodextrin (CyD) studies and drug-design research. These two methods are differential scanning calorimetry (DSC) and isothermal titration microcalorimetry (ITC). DSC and ITC can be con-... 

The greatly improved sensitivity of the modem microcalorimeters for both differential scanning miCTOcalorimetry (DSC) and isothermal titration microcalorimetry (ITC) has made their application highly useful. Titration microcalorimetry yields binding constants and, when applied as a function of temperafiire, full thermodynamic details for the binding process. DSC provides details about the distmbance of the bilayer system by the solubilized guest from which conclusions may be drawn about the preferred binding locations. 

When the time constants r and r" and T(t) are known, it is possible to determine the T (t) and T"(t) values consecutively, and thus P(t). The numerical differential correction method has also been applied to reproduce the thermokinetics in these calorimetric systems, in which time constant vary in time [258-264], such as the TAM 2977 titration microcalorimeter produced by Thermometric. These works extended the applications of the inverse filter method to linear systems with variable coefficients. In many cases [258-262], as in the multidomains method, as a basis of consideration the mathematical models used were particular forms of the general heat balance equation. 

The microcalorimeter offers a large choice of experimental vessels according to the applications to be run ... 

As it has been already mentioned, isothermal microcalorimeters are those calorimeters designed to work in the microwatt range under essentially isothermal conditions. Isothermal titration microcalorimetry (IT xC) is designed to connect extremely sensitive thermal measurement equipment (approx. 20-100 nanowatts) with an automatic syringe able to add reactants in successive injections to the solution with a precision of few nanoliters [32, 33]. Each injection produces specific heat effect, as shown in Fig. 10.5. The determination of heats evolved as a result of interaction between molecules is a main application of this variation of calorimetry. Consequently, isothermal titration calorimetry is a suitable method for studying degradations and biodegradations of versatile pollutants. 

In order to establish the correct functioning of the microcalorimeter, which is then connected to the volumetric adsorption unit, the sensitivity is evaluated determining the calorimeter constant. The calibration constant reports the voltage generated by the calorimeter when a heat flow is emitted from inside the micro-calorimetric cell. There are two methods to determine the calibration constant K by application of electric power and by the stationary method [9, 10]. 

R.D. Sanderson I don t have a microcalorimeter if I did, it would help tremendously. We have applied this technique in veiy many applications already it s great fun actually studying the orientation in very odd shapes where you have various different flow patterns, and this is what the engineering students are doing at the moment. 

Food scientists now realize that the simplistic view of such a mechanism is untenable to describe the behaviour of proteins in mixtures of components like foods. Furthermore, previous studies by protein chemists concerned isolated proteins, usually in aqueous solution at low concentrations and at pH values so far away from the isoelectric point as to discourage protein interactions and aggregation. For this reason, scanning microcalorimeters have been developed that have a detection limit low enough to study 1% w/w protein solutions [149], This, of course, up raises the question of the influence of concentration on DSC data and, therefore, the applicability of results obtained from one system to the other. It has been proved that water concentration plays an important role in the DSC response. Thus, it seems unlikely that conclusions based on dilute protein solutions examined by microcalorimetry can be directly transferable to much of the work done on food proteins at higher concentrations. 

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