Facilely Fabricated Luminescent Nanoparticle Thermosensor for Real-Time Microthermography in Living Animals

Abstract

This paper presents a high-sensitivity luminescent nanoparticle thermosensor capable of real-time microthermography in a living organism. Microthermography, or microscopically visualizing the temperature distribution within living cells, tissues, and organisms, is a promising technology to explore various physiological activities at the microscale. Using a facile nanoprecipitation method, we fabricated a polymer–nanoparticle embedding EuDT, a thermosensitive high-luminescence-emitter dye molecule, and rhodamine 800, a luminescent molecule excitable with low energy light and less sensitive to temperature. The nanoparticle thermosensor was largely exempted from the background noise, which is the undesired luminescence from the target biological sample, enabling direct acquisition of luminescence intensities from the thermosensor within the specified area of 68 μm × 68 μm on the muscle tissue of a living insect, i.e., real-time microthermography, without the need of subtracting background noise. Thus, we successfully mapped out the temperature shift due to the animal’s voluntary heat production. The nanoparticle thermosensor capable of in vivo temperature mapping must be a useful biological thermographic technology to explore microscopic heat productions in living organisms.

Lanthanide‐Based Thermometers: At the Cutting‐Edge of Luminescence Thermometry

“…A polymer incorporating Eu‐tris(dinaphthoylmethane)‐bis‐trioctylphosphine oxide as a temperature sensitive probe and rhodamine 800 (Rh800) to provide a reference emission band enabled the temperature monitoring and mapping with S m = 3.6% K −1 (at 298 K) and 1.4 < δT < 1.0 K. The polymer embedding the thermal probes successfully detected in vivo temperature shifts at localized sites in the muscle of a living beetle, either due to an external heat source (980 nm laser heating) or due to the animal's voluntary muscle‐activation (preflight preparation, Figure a–c). The Eu 3+ /Rh800 intensity ratio was recorded in 5 distinct positions of the muscle (Figure d,e) presenting a dynamics similar to that monitored by an IR thermal camera . Moreover, the same research group developed free‐standing nanosheets embedding the same emitting centers with superior flexibility and transparency, compared with the previous report, enabling the attachment onto the uneven surfaced living tissues without any glue ( Figure a,b) and the densification of muscle fibers covered by the thermometric film.…”

“…e) The corresponding temporal evolution of the normalized Eu 3+ /Rh800 intensity ratio in the three stimulations, followed in the ROI areas presented in (c). Adapted with permission . Copyright 2016, American Chemical Society.…”

“…In the last couple of years, we are observing a gradual shift of the emphasis of luminescence thermometry from the synthesis and general characterization of new thermographic phosphors toward the use of the technique for thermal imaging, early tumor detection, and as a tool for unveiling thermometer's features or details of their local surroundings. In the former case, examples include recording of in vivo thermal images, acquisition of subcutaneous thermal videos, and in vivo ischemia recognition in small animals . Early tumor detection becomes possible by transient thermometry using near‐infrared (NIR) emitting Ag 2 S nanocrystals .…”

GFP fluorescence peak fraction analysis based nanothermometer for the assessment of exothermal mitochondria activity in live cells

“…Luminescence nanothermometry emerged as a versatile tool for different kinds of applications including intracellular temperature measurements 6 , controlled photothermal and magneto-thermal therapy 3,10 , thermal conductivity measurements 11 , investigating muscle efficiency 12 , microscopic heat production in living organisms 13 and even for investigating the Brownian motion in ballistic regime 14 . Among the various types of temperature-dependent luminescence variables, the ratiometric technique is often chosen due to its robustness against photobleaching and compared to e.g.…”

Bright Dots and Smart Optical Microscopy to Probe Intracellular Events in Single Cells

“…Each nanoparticle contains temperature-sensitive fluorophores such as Eu-thenolytrifluoroacetonate (EuTTA) or Eu-tris(dinaphthoylmethane)-bis-trioctylphosphine oxide) (EuDT), of which emission intensities inversely correlate with temperature changes. In some cases, less temperature-sensitive fluorophores were also embedded in the same polymeric matrix to form a nanoparticle, whose surface is further covered by a hydrophilic polymer outer layer (Takei et al, 2014; Arai et al, 2015; Ferdinandus et al, 2016). Measurement of the temperature can be achieved by determining the reduction of emission intensity of EuTTA or EuDT, or by the ratio of the intensity of EuTTA or EuDT to that of the less temperature-sensitive fluorophores which act as internal references.…”