title: Isothermal titration calorimetry in nanoliter droplets with subsecond time constants.
abstract: We reduced the reaction volume in microfabricated suspended-membrane titration calorimeters to nanoliter droplets and improved the sensitivities to below a nanowatt with time constants of around 100 ms. The device performance was characterized using exothermic acid-base neutralizations and a detailed numerical model. The finite element based numerical model allowed us to determine the sensitivities within 1% and the temporal dynamics of the temperature rise in neutralization reactions as a function of droplet size. The model was used to determine the optimum calorimeter design (membrane size and thickness, junction area, and thermopile thickness) and sensitivities for sample volumes of 1 nL for silicon nitride and polymer membranes. We obtained a maximum sensitivity of 153 pW/(Hz)(1/2) for a 1 μm SiN membrane and 79 pW/(Hz)(1/2) for a 1 μm polymer membrane. The time constant of the calorimeter system was determined experimentally using a pulsed laser to increase the temperature of nanoliter sample volumes. For a 2.5 nanoliter sample volume, we experimentally determined a noise equivalent power of 500 pW/(Hz)(1/2) and a 1/e time constant of 110 ms for a modified commercially available infrared sensor with a thin-film thermopile. Furthermore, we demonstrated detection of 1.4 nJ reaction energies from injection of 25 pL of 1 mM HCl into a 2.5 nL droplet of 1 mM NaOH.
authors.affiliation: Department of Biomedical Engineering, VU Station B 351631, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Lubbers
authors.forename: Franz
authors.initials: F
authors.lastname: Baudenbacher
mesh_terms: D002151:Calorimetry; D008567:Membranes, Artificial; D036103:Nanotechnology; D011108:Polymers / Q000737:chemistry; D017655:Silicon Compounds / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D008567:Membranes, Artificial; D011108:Polymers; D017655:Silicon Compounds; C032734:silicon nitride