The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

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Diverse Applications of Nanomedicine

Biosynthesis and Bioconjugation to Biomedical Application Juan Zhou,‡,§ Yong Yang, and Chun-yang Zhang*,†,§ †College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China ‡State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China Single-Molecule Detection and Imaging Laboratory, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application

In this review we present new concepts and recent progress in the application of semiconductor quantum dots (QD) as labels in two important areas of biology, bioimaging and biosensing. We analyze the biologically relevant properties of QDs focusing on the following topics: QD surface treatment and stability, labeling of cellular structures and receptors with QDs, incorporation of QDs in living cells, cytotoxicity of QDs and influence of the biological environment on the biological and optical properties of QDs. Initially, we consider utilization of QDs as agents in high-resolution bioimaging techniques that can provide information at the molecular levels. The diverse range of modern live-cell QD-based imaging techniques with resolution far beyond the diffraction limit of light is examined. In each technique, we discuss the pros and cons of QD use and deliberate how QDs can be further engineered to facilitate their application in the respective imaging techniques and to produce significant improvements in resolution. Then we review QD-based point-of-care bioassays, bioprobes, and biosensors designed in different formats ranging from analytic biochemistry assays and ELISA, to novel point-of-care smartphone integrated QD-based biotests. Here, a wide range of QD-based fluorescence bioassays with optical transduction, elecrochemiluminescence and photoelectrochemical assays are discussed. Finally, this review provides an analysis of the prospects of application of QDs in selected important areas of biology.

Application of semiconductor quantum dots in bioimaging and biosensing.

A white-light-emitting diode (white LED) with good color rendering index is fabricated based on a blue LED combined with high-fluorescence CdS:Cu/ZnS quantum dots (QDs) and YAG:Ce phosphors. The reabsorption problem is overcome by the excellent optical properties and enlarged Stokes shift of the QDs with low absorption of light of wavelengths longer than 470 nm.

Doped quantum dots for white-light-emitting diodes without reabsorption of multiphase phosphors.

Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple analytes within a small, single sample volume. Thanks to the rapid development of nanotechnology, tremendous progress has been made in the multiplexed detecting capability, sensitivity, and photostability of suspension arrays. In this review, we first focus on the current stock of nanoparticle-based barcodes as well as the manufacturing technologies required for their production. We then move on to discuss all existing barcode-based bioanalysis patterns, including the various labels used in suspension arrays, label-free platforms, signal amplification methods, and fluorescence resonance energy transfer (FRET)-based platforms. We then introduce automatic platforms for suspension arrays that use superparamagnetic nanoparticle-based microspheres. Finally, we summarize the current challenges and their proposed solutions, which are centered on improving encoding capacities, alternative probe possibilities, nonspecificity suppression, directional immobilization, and “point of care” platforms. Throughout this review, we aim to provide a comprehensive guide for the design of suspension arrays, with the goal of improving their performance in areas such as multiplexing capacity, throughput, sensitivity, and cost effectiveness. We hope that our summary on the state-of-the-art development of these arrays, our commentary on future challenges, and some proposed avenues for further advances will help drive the development of suspension array technology and its related fields.

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Suspension arrays based on nanoparticle-encoded microspheres for high-throughput multiplexed detection.

Both disease diagnosis and therapeutic treatments require real-time information from assays capable of identifying multiple targets. Among various multiplexed biochips, multiplexed suspension assays of quantum dot (QD)-encoded microspheres are highly advantageous. This arises from the excellent fluorescent properties of the QDs incorporated into these microspheres, thus allowing them to serve as "QD barcodes". QD barcodes can be prepared through various approaches. However, the formulation of improved synthetic techniques that may allow more efficient preparation of QD barcodes with better encoding accuracy still remains a challenge. In this report, we describe a combined membrane emulsification-solvent evaporation (MESE) approach for the efficient preparation of QD barcodes. By combining the advantages of the MESE approach in controlling the barcode sizes with accurate encoding, a three-dimensional barcode library that integrates the signals of the forward scattering, fluorescence 1, and fluorescence 4 channels was established via flow cytometry. The five indexes of hepatitis B viruses were chosen as diagnostic targets to examine the feasibility of the QD barcodes in high-throughput diagnosis. On the basis of showing that singleplex detection is feasible, we demonstrate the ability of these QD barcodes to simultaneously and selectively detect a multitude of diverse biomolecular targets.

Highly efficient preparation of multiscaled quantum dot barcodes for multiplexed hepatitis B detection

NIR-emitting CdSeTe/CdS/ZnS core/shell/shell QD-encoded microbeads are combined with common flow cytometry with one laser for multiplexed detection of hepatitis B virus (HBV). A facile one-pot synthetic route is developed to prepare CdSeTe/CdS/ZnS core/shell/shell QDs with high photoluminescence quantum yield and excellent stability in liquid paraffin, and a Shirasu porous glass (SPG) membrane emulsification technique is applied to incorporate the QDs into polystyrene-maleic anhydride (PSMA) microbeads to obtain highly fluorescent QD-encoded microbeads. The relatively wide NIR photoluminescence full width half maximum of the CdSeTe/CdS/ZnS QDs is used to develop a 'single wavelength' encoding method to obtain different optical codes by changing the wavelengh and emission intensity of the QDs incorporated into the microbeads. Moreover, a detection platform combining NIR-emitting CdSeTe/CdS/ZnS QD-encoded microbeads and Beckman Coulter FC 500 flow cytometry with one laser of 488 nm is successfully used to conduct a 2-plex hybridization assay for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and a 3-plex hybridization assay for hepatitis B surface antibody (HBsAb), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb), which suggests the promising application of NIR QD-encoded microbeads for multiplex immunoassays.

NIR-emitting quantum dot-encoded microbeads through membrane emulsification for multiplexed immunoassays

By using paraffin liquid and oleic acid as the solvent and ligand, highly-fluorescent red to near-infrared (NIR)-emitting cadmium selenium telluride (CdSe1−xTex) alloyed quantum dots (QDs) with photoluminescence quantum yield (PLQY) up to 70% were successfully prepared. The as-prepared CdSe1−xTex QDs also demonstrated good optical stabilities against the temperature change and photobleaching due to their gradient “CdTe-rich core/CdSe-rich surface” quasi “core/shell” structure, which was confirmed by studying the alloying process of CdSe1−xTex QDs. Moreover, the as-prepared red to NIR CdSe1−xTex QDs were successfully incorporated into the carboxyl capped porous polystyrene (PS) microbeads to fabricate red to NIR-emitting microbeads with low in vitro cytotoxicity, and the biotinylated goat anti-mouse IgG could be specifically coupled to the optical encoded beads via mouse anti-human chorionic gonadotrophin connected to the carboxyl groups on the encoded microbeads successfully, which suggested promising application of CdSe1−xTex QDs in multiplexed bioassays.

Highly-fluorescent alloyed quantum dots of CdSe1−xTex synthesized in paraffin liquid: gradient structure and promising bio-application

Quantum dot (QD)-encoded microspheres play an important role in suspension arrays by acting as supports for various reactions between biomolecules With regard to QD-encoded microspheres utilized in suspension arrays, three key requirements are controllable size, abundant surface functional groups, and especially excellent fluorescence properties In this paper, narrowly dispersed poly(styrene-co-divinylbenzene-co-methylacrylic acid) (PSDM) microspheres with specific size, surface carboxyl groups, and porous structures were synthesized by seeded copolymerization In order to improve the incorporation efficiency of QDs within microspheres, we developed a swelling-evaporation approach in which the swelling process was combined with gradual evaporation of the solvent and thus gradual concentration of QDs in the dispersion solution This approach was demonstrated to be an efficient method for improving the fluorescence intensity of resultant microspheres compared with the use of swelling alone Moreover, the porous structure was shown to aid the penetration of QDs into the interiors of the microspheres Through this approach, microspheres encoded with either single or multiple wavelength-emitting QDs were fabricated effectively The suspension immunoassays were then founded based on the QD-encoded microspheres, by coating mouse antihuman chorionic gonadotropin as the probe for goat antimouse IgG detection The positive results determined by Luminex 100 and the low cytotoxicity of the QD-encoded microspheres demonstrated their great potential in suspension arrays

Efficient Incorporation of Quantum Dots into Porous Microspheres through a Solvent-Evaporation Approach

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/smll.201370114

Huasheng Xiao

Papers

Highly efficient preparation of multiscaled quantum dot barcodes for multiplexed hepatitis B detection

NIR-emitting quantum dot-encoded microbeads through membrane emulsification for multiplexed immunoassays

Highly-fluorescent alloyed quantum dots of CdSe1−xTex synthesized in paraffin liquid: gradient structure and promising bio-application

Efficient Incorporation of Quantum Dots into Porous Microspheres through a Solvent-Evaporation Approach

Quantum Dots: NIR‐Emitting Quantum Dot‐Encoded Microbeads through Membrane Emulsification for Multiplexed Immunoassays (Small 19/2013)