Nanocalorimetric platform for accurate thermochemical studies in microliter volumes

Abstract

A straightforward and general way for monitoring chemical reactions is via their thermal signature. Such approach requires however an experimental setup with a high thermal stability that simultaneously allows time-resolved heat detection with high sensitivity. We present a nanocalorimetric platform for accurate thermochemical studies of (bio-)chemical reactions in a miniaturized format (tens of microliter volume), characterized by a fast thermalization time to a preset temperature (< 30 minutes), an excellent base temperature stability (± 1 mK) and a fast sensing response time (few seconds). The platform is built around a commercial thermopile-based sensor chip, on which an open-well reservoir holding the sample is directly positioned. The sample is, prior to the experiment, pipetted into the reservoir, in which small aliquots of reagents are injected subsequently and sequentially via thermalized microfluidic conducts. The design of the platform is optimized by means of numerical simulations. Via thermoelectric calibration using a resistive heater positioned either on the sensor chip or in the reservoir, we obtain a maximum power sensitivity of 2.7 V/W and a heat limit of detection of 70 nW. The excellent functionality of the platform is demonstrated by measuring the reaction enthalpy of 1-propanol in water and the rate constant k and enthalpy change of the oxidation reaction of glucose catalyzed by glucose oxidase, showing good agreement with literature data. Our versatile platform may be applied to many thermochemical studies, including thermodynamic analysis and kinetic reaction analysis, and its ease of use will allow implementation of many different experimental protocols.

Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

“…Previously, the design of microcalorimetric chips has focused on the thermal optimization of the system rather than microfluidic aspects. This may explain why most chip calorimeters have been employed in monitoring chemical or biochemical reactions—for example, hydration of ethanol or propanol 44 , glucose oxidation by glucose oxidase 34 , or denaturation of protein 33 —and less on cell metabolism.…”

“…Current micro- and nanocalorimetric chips are designed as essentially miniaturized versions of instrumentation microcalorimeters. Their central focus being on measurement accuracy, they often include additional parts such as heaters, thermally insulating layers and PID controllers to ensure the thermal stability of the system 33 , 34 . The focus on accuracy comes at the expense of design flexibility of the sample chamber.…”

A High-Resolution Measurement System Designed for Semiconductor Microcalorimetry Sensors

“…The authors also created dedicated software in LabVIEW, which was used for the data acquisition. The same type of microcalorimeter was used to measure the heat that was generated by chemical and biological reactions in [22]. The proposed measurement and control system included an additional proportional-integral-derivative (PID) controller that is designed for temperature stabilisation at the level of ±1 mK of the chip holder.…”

“…The possibility of using the measurement platform was tested by measuring the heat generated during mixing of propyl alcohol with deionized water at concentrations that ranged from 0% to 69% for the propyl alcohol. In turn, in [24], the authors determined the power sensitivity of 2.7 V/W and a heat detection limit of 70 nW for their measurement and control system, which was dedicated to heat flow microcalorimeters. A drawback of the presented solution is that this measurement system is not portable and cannot be used in a broad range of conditions.…”