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Frontiers of Mechanical Engineering

ISSN 2095-0233

ISSN 2095-0241(Online)

CN 11-5984/TH

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2018 Impact Factor: 0.989

Front. Mech. Eng.    2017, Vol. 12 Issue (4) : 526-538    https://doi.org/10.1007/s11465-017-0451-0
REVIEW ARTICLE
Review of MEMS differential scanning calorimetry for biomolecular study
Shifeng YU1, Shuyu WANG2, Ming LU3, Lei ZUO1()
1. Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA
2. Department of Mechanical Engineering, Stony Brook University, Stony Brook, NY 11794, USA
3. Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY 11973, USA
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Abstract

Differential scanning calorimetry (DSC) is one of the few techniques that allow direct determination of enthalpy values for binding reactions and conformational transitions in biomolecules. It provides the thermodynamics information of the biomolecules which consists of Gibbs free energy, enthalpy and entropy in a straightforward manner that enables deep understanding of the structure function relationship in biomolecules such as the folding/unfolding of protein and DNA, and ligand bindings. This review provides an up to date overview of the applications of DSC in biomolecular study such as the bovine serum albumin denaturation study, the relationship between the melting point of lysozyme and the scanning rate. We also introduce the recent advances of the development of micro-electro-mechanic-system (MEMS) based DSCs.

Keywords differential scanning calorimetry      biomolecule      MEMS      thermodynamic     
Corresponding Author(s): Lei ZUO   
Just Accepted Date: 07 June 2017   Online First Date: 19 July 2017    Issue Date: 31 October 2017
 Cite this article:   
Shifeng YU,Shuyu WANG,Ming LU, et al. Review of MEMS differential scanning calorimetry for biomolecular study[J]. Front. Mech. Eng., 2017, 12(4): 526-538.
 URL:  
https://academic.hep.com.cn/fme/EN/10.1007/s11465-017-0451-0
https://academic.hep.com.cn/fme/EN/Y2017/V12/I4/526
Fig.1  Two typical commercial DSCs. (a) The MicroCal VP-DSC, it consists of the sample array, robotic arm for sample handling and the temperature scanning system [14]; (b) the TA DSC, it consists of a sample tray, robotic arm for sample handling and the chamber for thermal analysis [15]
Fig.2  The general model for DSC. (a) The schematic diagram for DSC which consists of sample and reference cells (the cells are located in a well-designed test chamber); (b) the thermal model for the DSC
Fig.3  Typical DSC curves of bimolecular reaction. (a) DSC thermogram for the hen lysozyme denaturation process; (b) schematic of the DSC thermogram observed for BSA denaturation process with the raw data and the separated two thermal domains after baseline subtraction (1 kcal=4.184 kJ) [29]
Fig.4  The DSC curves for lysozyme sample with different scanning rate ranges from 2 to 20 oC/min. (a) DSC curves of lysozyme sample with the concentration 20 mg/mL; (b) DSC curves of lysozyme sample with the concentration 10 mg/mL
Fig.5  Challenges to develop MEMS DSC compared to the conventional DSC. (a) Schematic set up for commercial macro DSC [35]; (b) microfluidic chamber device [36]; (c) suspended membrane for the MEMS DSC; (d) temperature sensing and heating unit [37]
Fig.6  Two typical microfluidic chamber fabrication method. (a) Glass based microfluidic chamber fabrication process; (b) PDMS microfluidic chamber fabrication process
Fig.7  (a) Microfluidic system for a novel nanocalorimeter [26]; (b) schematic view of the microfluidic system for a high sensitive microfluidic calorimeter [48]
Fig.8  Two temperature sensing examples in calorimetry application. (a) Four SiC thermistors form a Wheatstone bridge for the temperature measurement [47]; (b) 50 junctions of thermocouples are connected in series to build the thermopile to measure the differential temperature between the sample and reference cell [60]
Fig.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]
MEMS DSC workSample consumption/nLSensitivity/(V·W–1)Noise level in temperature/μKNoise level in power/nW
Lin’s group, 2015 [60]10004.7820
Lee’s group, 2016 [66]3048.0010
Lee’s group, 2014 [67]2008.17
Zuo’s group, 2016 [68]10006.0060.0040
Saito and Nakabeppu, 2015[69]Flow through100
Tab.1  Lists of most up to date MEMS DSC work
Fig.10  Various examples of MEMS DSC designed for biomolecular study. (a) High sensitivity calorimeter platform using V2O5 thin film thermistor was developed. The calorimeter platform Integrates a V2O5 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 [67]; (b) µ-calorimeter designed for the efficient coupling and detection of heat from the thermal elements for accurate characterization [68]; (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 [65]; (d) MEMS DSC design integrated vanadium oxide thermistors and flexible polymer substrates with microfluidics chambers for ultrasensitive biomolecular study [69]
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