High-sensitivity microfluidic calorimeters for biological and chemical applications.
High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.
Lee
Wonhee
W
Kavli Nanoscience Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Fon
Warren
W
Axelrod
Blake W
BW
Roukes
Michael L
ML
D002151:Calorimetry / Q000295:instrumentation*; D006358:Hot Temperature; D006868:Hydrolysis; D056656:Lab-On-A-Chip Devices; D000432:Methanol / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D014508:Urea / Q000737:chemistry; D014867:Water / Q000737:chemistry
D014867:Water; D014508:Urea; D000432:Methanol
Anal Chem. 2002 May 1;74(9):2190-7
12033326
Adv Protein Chem. 1992;43:313-61
1442323
Phys Rev Lett. 2001 Apr 30;86(18):4163-6
11328121
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9517-22
15210951
Electrophoresis. 2002 Oct;23(20):3461-73
12412113
Anal Biochem. 1989 May 15;179(1):131-7
2757186
Anal Chem. 2008 Apr 15;80(8):2728-33
18351750
Anal Chem. 2004 Jul 1;76(13):3756-63
15228351
Anal Biochem. 2008 Jun 1;377(1):33-9
18374654
Lab Chip. 2004 Oct;4(5):495-501
15472734
Biosens Bioelectron. 2004 Jul 15;19(12):1733-43
15142608
Anal Chem. 2001 Apr 1;73(7):1622-6
11321319