Micro-differential scanning calorimeter for liquid biological samples

Abstract

We developed an ultrasensitive micro-DSC (differential scanning calorimeter) for liquid protein sample characterization. This design integrated vanadium oxide thermistors and flexible polymer substrates with microfluidics chambers to achieve a high sensitivity (6 V/W), low thermal conductivity (0.7 mW/K), high power resolutions (40 nW), and well-defined liquid volume (1 μl) calorimeter sensor in a compact and cost-effective way. We further demonstrated the performance of the sensor with lysozyme unfolding. The measured transition temperature and enthalpy change were in accordance with the previous literature data. This micro-DSC could potentially raise the prospect of high-throughput biochemical measurement by parallel operation with miniaturized sample consumption.

Review of MEMS differential scanning calorimetry for biomolecular study

“…9 (a) Sensitivity calibration of a MEMS DSC using Joule heat [64]; (b) DSC scans showing the analysis of spray-dried lactose at a variety of high heating rates using fast scan DSC [65] 4.4 Recent MEMS DSC research Currently, MEMS DSC are developed for high throughput calorimetry, super sensitive biochemical sensing and cellular level measurement applications. There are significant works done towards these goals which are listed in Table 1 [60,[66][67][68][69]. They employ novel structures, temperature sensing materials to achieve high thermal performance.…”

“…Some of these designs are show in Fig. 10 [64, [66][67][68]. Figures 10(a) and 10(b) are MEMS DSC fabricated on suspended Si 3 N 4 membrane.…”

“…(a) High sensitivity calorimeter platform using V 2 O 5 thin film thermistor was developed. The calorimeter platform Integrates a V 2 O 5 thermistor with a high temperature sensitivity of -2.2%/K with a vacuum insulated, suspended SiN membrane structure enabled a low thermal conductance of 12 µW/K and achieves direct detection of 10 nW [66]; (b) µ-calorimeter designed for the efficient coupling and detection of heat from the thermal elements for accurate characterization [67]; (c) MEMS DSC combines highly sensitive thermoelectric sensing, on-chip self-calibration, and microfluidic regulation for thermodynamic characterization of biomolecular samples on a minimized scale [64]; (d) MEMS DSC design integrated vanadium oxide thermistors and flexible polymer substrates with microfluidics chambers for ultrasensitive biomolecular study [68] the environment will generate random signal which can affect the result. Figures 10(a) and 10(b) employ vanadium oxide based thermistor as the temperature sensor.…”

Heat and pressure-resistant room temperature irreversible sealing of hybrid PDMS–thermoplastic microfluidic devices via carbon–nitrogen covalent bonding and its application in a continuous-flow polymerase chain reaction

“…Furthermore, PDMS can easily bond to other PDMS or silicon-like substrates by a simple surface activation method, and this property can be useful for the fabrication of disposable low-cost LOCs. 2 Thermoplastics are also materials for hybrid frameworks, and these substrates have many attractive properties, such as high optical transparency, low thermal conductance, and good biocompatibility, which make them promising materials for bio-microelectromechanical system (bio-MEMS) calorimeters, 3 electrochemical LOC, 4 and other biosensor applications. 5 Despite the many advantages of PDMS and thermoplastics, the strong sealing between the two substrates is one of the important aspects of the fabrication of LOCs.…”

Fast and accurate enzyme activity measurements using a chip-based microfluidic calorimeter

“…This has been achieved by applying microfluidic technology. New chip-based https://doi.org/10.1016/j.ab.2017.12.028 Received 8 June 2017; Received in revised form 14 December 2017; Accepted 18 December 2017 microfluidic calorimeters have been developed [9][10][11] that have a sample volume of less than 20 μl and a thermal equilibration time of a few seconds. Fig.…”