Quantum Dots: Part 4 of My Notes from 2017 MIT Health Sensing & Imaging Conference Sept. 19-20, 2017.

Quantum Dots: Applications in Bioimaging Beyond Visible Light

Moungi Bawendi, Lester Wolfe Professor of Chemistry, MIT Department of Chemistry

Quantum dots are small particles of semi-conductors, discovered around 30 years ago.

An exciton is a bound state of an electron and an electron hole which are attracted to each other by the electrostatic Coulomb force. It is an electrically neutral quasiparticle that exists in insulatorssemiconductors and in some liquids. The exciton is regarded as an elementary excitation of condensed matter that can transport energy without transporting net electric charge

An exciton can form when a photon is absorbed by a semiconductor, or applying an electrical current. They emit light – if lit with blue, the emission is in the red wavelength eg “down-shifting”. You can also pull the electron out with a magnet.

Nanocrystals are important because of their absorption spectra – depending on their size they release different colours of light, with large particles releasing red – this is described as “tunable light”. Any colour can be used to excite them. They are also photo-stable.

Quantum dots can also emit in the IR spectrum.

Applications today

In the light bulb initially. Then in LED televisions – used white LEDs to create backlight, then filters in front to create RGB. Samsung put a blue LED and a rail of quantum dots in green and red to change the colour. The kindle used a similar technology. All Samsung QLed TVs use this tech.

In vitro experimentation

Labelling cytotubules and nuclei using QDs

In-vivo experimentation

Labelling and imaging single haematopoietic precursor cells endogenously in live mice, to avoid taking them out of the mouse and causing differentiation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321304/

Short-wave infrared (SWIR) light – in gas camera

  • Absorbed differently (picture of apple bruise)

Image result for SWIR apple bruise

  • Scattered less

SWIR is optimal for imaging because it is better than other types of light in terms of:

  • speed (signal limited due to attenuation)
  • penetration depth and resolution
  • sensitivity – auto-fluoroscence can mask the molecule you are trying to identify

Applications

High speed SWIR imaging – contact free optical cardiography in awake mice… 

https://www.nature.com/articles/s41551-017-0056

Imaging of physiology in awake and unrestrained mice at high speed.

Glioblastoma multiforme in cranial window model

  • inject probe into mouse
  • allow to clear
  • track the QDs in the tumour vasculature of the brain

Show the differences in the vasculature of the healthy and tumour brain.

Traditional NIR-dyes have several disadvantages for use as fluorescent probes: low solubility in aqueous solution, low quantum yield, and low photostability. For example, ICG, the most widely used NIR-dye only provides a quantum yield of 1.2% [6] in blood. In addition, the photostability of ICG is very poor and the fluorescence of ICG in aqueous solution diminishes within several days under room right [7].

Recent developments in synthetic techniques for NIR-emitting QDs have paved the way for use of NIR QDs as fluorescence contrast agents for in vivo imaging [816]. In comparison with organic NIR dyes, NIR QDs are highly bright and resistant to photobleaching [1113]. Kim et al. first reported the biological utility of NIR QDs (CdTe/CdSe) for sentinel lymph node imaging in a mouse and pig.

These QDs are mostly synthesized by heating appropriate organometallic precursors in organic solvents [e.g. trioctylphosphine oxide (TOPO) and trioctylphosphine (TOP)] [2728]. Thus the resulting NIR QDs are very hydrophobic and insoluble to water. For the application of NIR QDs for in vivo imaging, the hydrophobic surface of the QDs should be modified to be hydrophilic.

Jin et al. 2008. Preparation and Characterization of Highly Fluorescent, Glutathione-coated Near Infrared Quantum Dots for in Vivo Fluorescence Imaging.Int J Mol Sci. 2008 Oct; 9(10): 2044–2061.

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