Quantum Dots: Heralding a Brighter Future for Clinical Diagnostics

Tamer M Samir; Mai MH Mansour; Steven C Kazmierczak; Hassan ME Azzazy

Nanomedicine. 2012;7(11):1755-1769.

Conclusion

QDs have demonstrated extensive potential in biomedical applications owing to the combination of their unique photophysical properties and the ability to render them biocompatible and specific by conjugation to various biomolecules. Their use is underway in various immunological and molecular assays for different pathogens and biomarkers, in multiple strategies. For the clinical laboratory, QDs represent attractive tools for ultrasensitive multiplexed diagnostics. Additionally, the combined utilization of QDs with their unique optical properties and microfluidics would aid the development of miniaturized sensitive bioanalysis systems and aid efforts towards their use for point-of-care testing, which would allow the movement of testing processes closer to patients in remote locations with limited infrastructure and decrease reliance on central laboratories. Also, point-of-care testing would support field testing in disease outbreak areas. Commercial availability of various types of QDs is substantially increasing and a large body of successful studies of clinical utility has already built up. These factors are highly conducive and indicative of a more significant role of QDs in the future of bioanalysis. Although their promising future for in vivo imaging is clouded by toxicity concerns, which are actively being addressed, the next decade in clinical laboratory medicine could likely see a noticeable advancement in the use of QDs.

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Table 1. Summary of quantum dot–protein/peptide conjugation approaches.
Biomolecule	QD type	QD surface cap	Strategy	Application	Ref.
Transferrin protein	CdSe/ZnS	Mercaptoacetic acid	Crosslinking of QD surface carboxylic group to reactive amine groups	Labeling and imaging of cultured HeLa cells	[19]
TAT peptide	CdTe	Thiol	Crosslinking using EDC	Labeling and imaging of human hepatocellular carcinoma (QGY) cells and human breast cancer (MCF7) cells	[24]
Phytochelatin-related peptides	CdSe/ZnS	TOPO	Direct binding with thiolated peptide containing cysteine residues	Labeling and imaging of HeLa cells	[13]
Multifunctional peptides contain protease recognition/cleavage sequence for caspase-1, collagenase and chymotrypsin	CdSe/ZnS	DHLA	Self-assembly of peptides containing amino-terminal hexahistidine domain on DHLA-capped QDs	Detect proteolytic activity of caspase-1, thrombin, collagenase and chymotrypsin	[28]
Maltose binding protein	CdSe/ZnS	DHLA	Self-assembly of QD and protein due to electrostatic attraction between the negatively charged DHLA cap on the QD and positively charged leucine zipper tail of the protein	An alternative conjugation strategy for conjugating proteins to the surface of CdSe/ZnS DHLA-capped QDs other than using EDC crosslinker	[20]
Concanavalin A protein	CdTe	TGA	Crosslinking of QD surface carboxyl group to reactive amine groups of concanavalin A	FRET-based glucose biosensor	[9]

DHLA: Dihydrolipoic acid; EDC: 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide; FRET: Förster resonance energy transfer; QD: Quantum dot; TGA: Thioglycolic acid; TOPO: Trioctylphosphine oxide.

Table 2. Selected quantum dot-based diagnostic applications.
QDs	Application	Ref.
CdTe/CdS QDs conjugated to goat anti-mouse IgG secondary antibodies	In sandwich and reverse-phase immunoassay formats, cancer biomarkers CEA and AFP were detected using respective mouse antibodies. The detection was carried out on a microfluidic chip with femtomolar sensitivity for both biomarkers When applied to human serum the detection limit was approximately 2.5 pM for CEA, and 250 fM for both AFP and CEA in buffer. Commercial ELISA kits have detection limits of 5 and 7 pM for CEA and AFP, respectively Quantitative determination of CEA and AFP was simultaneously achieved (concentration range: 25 fM to 25 nM)	[67]
CdSe/ZnS/SiO₂ QDs	QDs were used to count bacterial cells (Escherichia coli) in samples instead of the old viable count culture methods The method used glutaraldehyde as a crosslinker to covalently bind QDs to the bacteria. The bacteria were then mixed with the QD–glutaraldehyde mixture and the excess QDs were removed by ultrafiltration Direct bacterial counting with a detection limit of 3 × 10² CFU/ml (10–20-times lower than that of plate counting method) was used Reduction of detection time to 2 h	[68]
CdTe QDs conjugated to oligonucleotides (molecular beacon structure)	Simultaneous detection of single-base mutations in synthetic DNA targets using QDs conjugated to oligonucleotide molecular beacons and capillary electrophoresis analysis Detection limit of 16.2 pg of DNA	[69]