Microdevice for small-scale calorimetric measurement

This technology is a microelectromechanical systems (MEMS)-based calorimeter for measuring the thermodynamic properties of chemical and biochemical reactions at microliter scale.

Unmet Need: Simple, accurate calorimetric device with low sample consumption

Current calorimetric methods rely on large, complex instruments that typically require large sample quantities for accurate measurement, reducing throughput and raising experimental costs. Additionally, most devices use direct current (DC) to modulate temperature at a constant rate, which prevents samples from reaching an equilibrium state at each temperature. This results in low signal-to-noise ratios and less accurate thermodynamic measurements.

The Technology: Integrated miniature calorimeter device for accurate thermodynamic characterization of chemical and biochemical reactions

This technology is a MEMS-based device that integrates heating elements and temperature sensors on a single chip for simple and accurate calorimetric measurements. Using isothermal titration calorimetry, this technology can determine thermodynamic properties such as enthalpy and entropy changes, binding constants, and reaction stoichiometry. The device features two isolated microchambers compatible with liquid samples that can be utilized for sample and reference comparisons of microliter-sized samples. In contrast to existing methods, this technology uses an alternating current (AC) approach that allows samples to reach quasi-equilibrium, which improves the accuracy of thermodynamic measurements and delivers a good signal-to-noise ratio. In sum, this technology provides a compact system for accurate thermodynamic characterization of chemical and biochemical reactions for high throughput analysis.

A prototype of the device has been used to characterize the thermodynamics of the binding of ribonuclease A with cytidine 2’-monophosphate.

Applications:

• Determining thermodynamic properties of chemical reactions
• Quantifying evolution of heat during biological processes such as ligand binding or protein folding
• Measuring thermodynamic interactions of proteins
• Examining thermal transitions of polymers
• Portable and disposable calorimeter device

Advantages:

• Heating and temperature sensing elements integrated within the device
• Requires small, microliter sample size
• Larger signal-to-noise ratio
• Improved accuracy
• Compatible with liquid samples
• Simple miniaturized device design
• Works with high throughput systems

Lead Inventor:

Qiao Lin, Ph.D.

Patent Information:

Patent Issued

Related Publications:

• Wang B, Jia Y, Lin Q. “A microfabrication-based approach to quantitative isothermal titration calorimetry” Biosens Bioelectron. 2016 Apr 15;78: 438-446.

• Jia Y, Wang B, Zhang Z, Lin Q. “A polymer-based MEMS differential scanning calorimeter” Sens Actuators, A. 2014 Jul 23;231: 1-7.

• Wang B, Lin Q. “Temperature-modulated differential scanning calorimetry in a MEMS device.” Sensors and Actuators B: Chemical. 2013 Apr;180: 60-65.

• Wang B, Lin Q. “A MEMS differential scanning calorimetric sensor for thermodynamic characterization of biomolecules.” Journal of Microelectromechanical Systems. 2012 Jun;21(5): 1165-1171.

• Wang L, Wang B, and Lin Q. “Demonstration of MEMS-Based Differential Scanning Calorimetry for Determining Thermodynamic Properties of Biomolecules,” Sensors and Actuators B: Chemical. 2008 Sept;134(2): 953-958.

Tech Ventures Reference:

• IR M11-060, M11-112, CU12090, CU13356, CU15102

• Licensing Contact: Richard Nguyen