Molecular thermometry

Abstract

Conventional temperature measurements rely on material responses to heat, which can be detected visually. When Galileo developed an air expansion based device to detect temperature changes, Santorio, a contemporary physician, added a scale to create the first thermometer. With this instrument, patients' temperatures could be measured, recorded, and related to changing health conditions. Today, advances in materials science and bioengineering provide new ways to report temperature at the molecular level in real time. In this review, the scientific foundations and history of thermometry underpin a discussion of the discoveries emerging from the field of molecular thermometry. Intracellular nanogels and heat sensing biomolecules have been shown to accurately report temperature changes at the nanoscale. Various systems will soon provide the ability to accurately measure temperature changes at the tissue, cellular, and even subcellular level, allowing for detection and monitoring of very small changes in local temperature. In the clinic, this will lead to enhanced detection of tumors and localized infection, and accurate and precise monitoring of hyperthermia-based therapies. Some nanomaterial systems have even demonstrated a theranostic capacity for heat-sensitive, local delivery of chemotherapeutics. Just as early thermometry rapidly moved into the clinic, so too will these molecular thermometers.

Figure 1

Relative sizes of cells, proteins, and nanomaterials discussed in this review. A. Mammalian cell-10-110µm, B. Bacterium-1-5µm, C. EGFP-300nm diameter, D. QD-5-50nm (1/2 to 1/20 the size of the period)

Figure 2

Generalized structural motif representing how some engineered polymeric hydrogels respond to temperature shifts as judged by water exclusion. The fluidity of hydrogels is governed by weak electrostatic interactions between water and the polymers comprising the gel. When temperature reaches a “gel” threshold, water and polymer order undergoes formidable structural rearrangements. This behavior is parallel to the thresholds observed where pure substances experience conventional phase changes.