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Progress in Chemistry 2019, Vol. 31 Issue (2/3): 283-299 DOI: 10.7536/PC180712 Previous Articles   Next Articles

Functional Nanomaterials Based Suspension Array Technology

Weijie Wu, Yuankui Leng, Mengfei Shen, Wanwan Li**()   

  1. 1. The State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
  • Received: Online: Published:
  • Contact: Wanwan Li
  • About author:
    ** E-mail:
  • Supported by:
    National Natural Science Foundation of China(81371645); National Natural Science Foundation of China(81671782); National Key Research and Development Program of China(2017YFA0205304); Clinical Research Plan of SHDC(16CR3057A); Medicine & Engineering Cross Research Foundation of Shanghai Jiao Tong University(YG2017ZD02)
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Suspension array or liquid biochips technique based on spectrometrically encoded microspheres plays a prominent role in simultaneously high-throughput multiplexed detection of multiple analytes within a small, single sample volume. It is a quite powerful tool for genes analysis, proteins profiling, disease early diagnosis, treatment monitoring and so on, due to its faster binding kinetics, high-throughput multiplexed detection, high detection sensitivity, and good reproducibility. Commercial suspension array platforms based on organic dye-encoded microspheres show various limitations such as limited encoding capacity, sensitivity, photostability, requirement of instruments with multiple excitation, tedious color compensation processes, etc. Substantial development has been achieved in improving the multiplexed detecting capability, detection sensitivity, and automatic platform of suspension arrays due to the rapid growth of nanotechnology and nanomaterials. In this review, we systematically introduce the recent progress on functional nanomaterials based suspension array technology, including functional nanoparticles-encoded microspheres and their fabrication technologies, design and regulation of suspension arrays. At last, we make a summary of the current challenges and their possible solutions in suspension array technology. We hope that our review on the recent progress, current challenges, possible solutions and the future prospects of suspension array based on encoded microspheres, will help drive the development of suspension array technology and its related fields.

Key words: suspension array, encoded microspheres, functional nanomaterials
Fig. 1 Schematic illustration of suspension array platform. The target of interest is identified by the barcode signal and quantified by the label signal[2]
Table 1 Comparison of different encoding nanoparticles(encoding methods)
Encoding elements Advantages Disadvantages ref
Organic dyes Good batch uniformity,
easy for encoding and decoding		 Multiple excitation; poor stability; limited encoding capacity 4
Quantum dots High encoding capacity; single excitation;
easy for encoding and decoding		 Energy transfer among different QDs(FRET or reabsorption) 46
UCNPS Low background interference;
single NIR excitation;		 Limited suitable reporter 60
Life-time Low background interference Low decoding speed 68
SERS High encoding capacity Cross-talk between barcodes and reporter 90
Structure-color High stability Limited encoding capacity 35
Fig. 2 (a) The most commonly used encoding principle utilizes colors and intensity levels;(b) A 3D encoding method that combines colors, intensity levels, and microsphere sizes[11,12,47]
Fig. 3 Fluorescence spectrum obtained from NaYF4:Yb/Ho/Tm(with different Tm doping amounts) upconversion nanocrystal encoded beads. Both the absolute intensities and relative intensity ratios of different emissions are used for coding purposes[60]
Fig. 4 (a) Eu-LRET(lanthanide-based resonance energy transfer) life-time barcodes;(b) τ-dots barcodes[68,75]
Fig. 5 Supermultiplexed optical barcoding with polyynes.(a) Chemical structures of 20 polyynes with distinct Raman frequencies, which are termed Carbon rainbow.(b) Raman peaks of Carbow in the silent spectral window.(c) Polymer beads are encoded by combinatorial loading of polyynes.(d) Spectral barcoding of polyynes at ten frequencies and three intensities(0, or 1 or 2) with SRS readout [93]
Fig. 6 (a) Suspension assay based on SERS barcode microsphere;(b) Multiplexed detection by using SERS dots as barcode labels;(c) NanoplexTMbiotag[98,99]
Fig. 7 (a) Reflection spectra of the opal photonic crystal beads(PCBs) composed of silica nanoparticles with different sizes;(b) SEM image of opal PCB surface;(c) Digital image of the seven kinds of inverse-opaline PCBs in water;(d) SEM image of the inverse-opaline PCBs surface[35,106]
Table 2 Comparison of different synthesis methods for fluorescent encoded microbeads
Methods Synthetic steps Ease of
barcoding		 Bead
monodispersity		 Yield Stability Problems ref
Swelling 3 or more Difficult Excellent(<3%) High Poor Poor stability,
limited encoding capacity		 12
Polymerization 2 Easy Poor High Good Poor monodispersity 119
Layer-by-layer More than 3 Easy Excellent(<3%) High Good limited encoding capacity 114
Microfluidic 1 Easy Good(<10%) Low Good Difficult to get smaller microbeads(<4 μm) 46
Membrane emulsification 1 Easy Good(<10%) Enough Good Undefined 11
Fig. 8 Schematic illustration of the fabrication of nanoparticle-composite microspheres by using microfluidic technique. Uniform single emulsions:(a) a concentration-controlled, flow-focusing(CCFF) device for the preparation of QD barcodes;(b) Lanthanide nanophosphor-encoded microspheres synthesis by using a microfluidic device; Uniform double emulsification:(c) Anisotropic magnetic barcode microspheres;(d) Multicore-encoded microsphere with red, green, and blue opal photonic crystal; cores;(e) Multicore photonic crystal microspheres[46,108,126,130]
Fig. 9 Schematic illustrating the preparation of carboxylated QD barcodes by SPG membrane emulsification-solvent evaporation approach[11]
Fig. 10 Overview of the smartphone device utilizing quantum dot barcodes.(a) Two excitation sources excite the quantum dot barcoded signal and reporter signal respectively, the optical signal is collected by a set of objective and eyepiece lenses, imaged using a smartphone camera;(b) Image of the smartphone device utilizing quantum dot barcodes [191]
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