Water-soluble nanoscale quantum dots for imaging and biomedical applications

Overview

Quantum dots (QDs) are inorganic nanoparticles that emit light at a specific wavelength when excited by light. Typically, they are synthesized using multi-step processes and hazardous organic solvents. These organic solvents must be removed prior to conjugating QDs with antibodies and other ligands for use in biological imaging applications. These multiple production steps make QDs expensive and limit their use.

 

To overcome these limitations and reduce the cost of QD manufacturing Drexel University’s researchers have developed an economic, direct synthetic method for producing water-soluble QDs that are ready for bioconjugation. Drexel’s methods can produce aqueous, highly luminescent metal sulfide (MS) QDs, (AQDs) with emission wavelengths varying from 400 nm to 700 nm. MS QDs are capped with thiol-containing charged molecules in a single step. The resultant AQDs exhibit no undesirable broadband emissions at higher wavelengths, a feature not attained by previous aqueous synthesis methods. AQDs range in size from 4 nm to 20 nm, and are stable in biological fluids over a long period of time. The metal in MS can be the traditionally used cadmium (Cd) or its non-toxic alternative, zinc (Zn). While the variations in composition change optical parameters, nevertheless, the non-toxic ZnS AQDs with good photoluminescence properties have been produced.

 

Further variations in the composition and methods of manufacturing resulted in production of near-infrared (NIR)-emitting AQDs. These included CdS-, ZnS-, CdSe-, ZnSe-, CdPbS- and SnS-based quantum dots capped with 3-mercaptopropionic acid (MPA), which stabilizes the AQDs in water. Such in situ stabilization of AQDs without the need for solvent exchange or ligand exchange makes Drexel AQDs ready for bioconjugation. Additional methods of AQDs manufacturing using different capping agents have been developed as well.

Applications

  • Cell and tissue staining, immunohistochemistry using AQDs as flourophores

  • Tissue imaging, including in vivo imaging using non-toxic NIR AQDs
  • Tumor margin detection using cancer cell-specific AQDs (see Tech ID 10-1266 and ref. 4 below for more details)

Advantages

  • Greatly simplified one-step manufacturing process
  • No need for hazardous solvents, environmentally friendly
  • Small particle size (4-20 nm) and very bright light emission

  • Bioconjugation-ready
  • Adjustable emission characteristics in the visible and near-infrared spectra

Intellectual Property and Development Status

United States Issued Patent- 7,335,345

United States Issued Patent- 8,865,477

United States Issued Patent- 9,082,918

References

G. Au et al., Quantitative assessment of Tn antigen in breast tissue micro-arrays using CdSe aqueous quantum dots. Biomaterials 2014 Mar 8; 35(9):2971-80.

G. Au, W. Shih, W-H. Shih, High-conjugation-efficiency aqueous CdSe quantum dots. Analyst 2013 Nov; 138(24):7316-25.

G. Au et al., Aqueous CdPbS quantum dots for near-infrared imaging. Nanotechnology 2012 Jul 18; 23(27):275601.

G. Au et al., Assessing breast cancer margins ex vivo using aqueous quantum-dot-molecular probes. Int J Surg Oncol 2012 24; 2012:861257.

H. Li et al., Cytotoxicity tests of water soluble ZnS and CdS quantum dots. J Nanosci Nanotechnol 2011 Apr; 11(4):3543-51.

Commercialization Opportunities

 

Contact Information

 

Alexey Melishchuk, PhD

Associate Director, Licensing

Office of Technology Commercialization

Drexel University

3180 Chestnut Street, Suite 104

Philadelphia, PA 19104

T: 215-895-0304

amelishchuk@drexel.edu

 

For Information, Contact:

  • Alexey Melishchuk
  • Associate Director, Licensing
  • Drexel University
  • am633@drexel.edu

Inventors:

Keywords: