A Micromachined Picocalorimeter Sensor for Liquid Samples with Application to Chemical Reactions and Biochemistry

Abstract

Calorimetry has long been used to probe the physical state of a system by measuring the heat exchanged with the environment as a result of chemical reactions or phase transitions. Application of calorimetry to microscale biological samples, however, is hampered by insufficient sensitivity and the difficulty of handling liquid samples at this scale. Here, a micromachined calorimeter sensor that is capable of resolving picowatt levels of power is described. The sensor consists of low‐noise thermopiles on a thin silicon nitride membrane that allow direct differential temperature measurements between a sample and four coplanar references, which significantly reduces thermal drift. The partial pressure of water in the ambient around the sample is maintained at saturation level using a small hydrogel‐lined enclosure. The materials used in the sensor and its geometry are optimized to minimize the noise equivalent power generated by the sensor in response to the temperature field that develops around a typical sample. The experimental response of the sensor is characterized as a function of thermopile dimensions and sample volume, and its capability is demonstrated by measuring the heat dissipated during an enzymatically catalyzed biochemical reaction in a microliter‐sized liquid droplet. The sensor offers particular promise for quantitative measurements on biological systems.

Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

“…However, traditional microcalorimeters are expensive, large and bulky machines, and are hardly compatible with other characterization methods (e.g., optical density for microbial cultures). In order to overcome these, microcalorimetric chips 20 , 21 , nanocalorimeters 12 , 22 , and picocalorimeters 23 have been developed. These systems have allowed important scientific progress such as single cell thermal power measurements 20 , 23 .…”

“…In order to overcome these, microcalorimetric chips 20 , 21 , nanocalorimeters 12 , 22 , and picocalorimeters 23 have been developed. These systems have allowed important scientific progress such as single cell thermal power measurements 20 , 23 . Further research has been conducted on different biologically relevant exothermic chemical reactions in microcalorimetric chips 22 – 25 , both in open-type chips 26 – 29 , which are limited to experiments of a few minutes, and closed-type chips.…”

Dissipation and energy propagation across scales in an active cytoskeletal material

“…Active cytoskeletal materials display a broad range of nonequilibrium dynamics that are only possible due to the injection of energy at the microscale ( 1 – 9 ). We study the energetics of a well-characterized active material by leveraging a recently developed micromachined picocalorimeter sensor ( 10 ) to directly measure the total thermal dissipation of this material in its nonequilibrium steady state ( Fig. 1 A and B and Materials and Methods ).…”

Dissecting flux balances to measure energetic costs in cell biology: techniques and challenges

“…The temporal resolution of isothermal calorimeters is highly dependent on sample volume. High-sensitivity and low-volume (∼1 𝜇L) calorimeters have time resolution on the order of seconds [90][91][92], but the time resolution for larger-volume microcalorimeters is on the order of hours. Recent devices have achieved sensitivities on the order of 200 pW [90][91][92], which is sufficient to measure the output from single C. elegans or Drosophila embryos, though single-cell measurements for microbes remain out of reach.…”

“…In open-chip calorimetry, evaporation can be a significant source of error. For the lowest-volume and most sensitive chip-based calorimeters, with sample volumes less than 1 𝜇L, the temperature gradient across the thermopile used to read out a signal is on the order of 1 mK [90]. Thus, even small external temperature gradients, heat sources, or heat losses can significantly impact the measurement.…”