University of Illinois at Chicago
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The Role of Colloidal Stability and Charge in Functionalization of Aqueous Quantum Dots

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journal contribution
posted on 2019-01-14, 00:00 authored by Preston T. Snee
Semiconductor quantum dots (QDs), also known as nanocrystals, have unique photophysical properties that have allowed them to find utility in many applications, including television and display technologies. They also have significant potential as imaging agents in the biomedical field. To gain the most value from the use of QDs as health-related fluorescent probes, they must be biologically targetable and sensitive to metabolic analytes such as pH and O2, and the resulting signal must be quantifiable. To achieve these goals, QDs need to be conjugated to vectors such as antibodies or environmentally sensitive chromophores. Until recently, the functionalization of these nanomaterials required a complex fully “bottom-up” approach beginning with the synthesis of the QDs and subsequent manipulations. To simplify this process, our group set out to develop straightforward methods to prepare functionalized nanomaterials for biological imaging and sensing using low-cost, commercially available aqueous QD dispersions. In this Account, we review the common problems and likely solutions related to functionalization of QDs in water with chemical and biological vectors. Early in our investigations, we found that established protocols using a commercially available activating reagent resulted in either low reaction yields or QD precipitation. This was a consequence of the perturbation of the QDs’ surface charges by the activating reagent and the conjugation substrate. These surface charges are derived from the anionic surfactants that are commonly employed for encapsulating water-soluble nanomaterials. Thus, cancellation of the surface charges by reagents or substrates results in colloidal instability. To address this problem, we devised conjugation methods that do not alter the overall charge balance of the system. Incorporating reactive moieties directly into the QD’s water-solubilizing polymer encapsulants negates the need for destabilizing activators, allowing for functionalization of aqueous samples without precipitation. The most successful approach was realized using neutral activating reagents, such as poly(ethylene glycol) carbodiimide (PEG-CD). PEG-CD binds to the carboxylic acid coating of water-soluble QDs, which primes them for amide bond formation with amine-functionalized substrates. Most importantly, this method can be applied to commercially available aqueous QDs. Using this method, we achieved reaction yields as high as 95%, allowing us to demonstrate a wide-range of QD functionalities and applications for chemical and biological sensing. Conjugation of environmentally sensitive dyes to water-soluble QDs results in reversible and ratiometrically reporting fluorescent probes for metabolic analytes such as pH, bisulfide, and O2. QDs can also be functionalized with proteins for passive cell delivery or coated with poly(ethylene glycol) to enhance biocompatibility for in vivo studies. In the future, these capabilities may be combined to realize the full potential of quantum dot nanotechnology for biological discovery.


This work was supported by the University of Illinois at Chicago, the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust, and Colgate-Palmolive.


Publisher Statement

Copyright @ American Chemical Society


Snee, P. T. (2018). The Role of Colloidal Stability and Charge in Functionalization of Aqueous Quantum Dots. Accounts of Chemical Research, 51(11), 2949-2956. doi:10.1021/acs.accounts.8b00405


American Chemical Society


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