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Researchers devise an ultrasensitive detection method to analyze the biomolecules

The research offers a promising strategy for the early diagnosis of cancer

Suspension array technology (SAT), a platform constructed by plugging microbeads into flow cytometry system, offers a new approach for large-scale screening applications. Suspension array is widely considered as the evolution of planar microarray due to its advantage in faster binding kinetics, lower sample volume needed, and multiplexing detection ability by optically encoding microbeads with combinations of fluorescent materials and decoding with flow cytometry.

However, one important limitation for SAT is its relatively low detection sensitivity due to the limited number of fluorescence dyes bound to one bead. Thus, improving the detection sensitivity is always of great importance for further improvement of the SAT. Despite the successful integration of PEF mechanism into planar microarrays for bio-sensing applications, PEF-based SAT bioassay platform, to the best of our knowledge, has been relatively less explored thus far until a few recent reports, in which gold-coated glass beads were developed for SAT-based bio-detection. However, the practical applications of the reported PEF-SAT would be hindered by complicated sample preparation procedures and tedious centrifugation steps for collection of beads. During this process, the inefficient recovery of microbeads would become a problem especially for detection of very small amounts of samples.

That challenge has been solved by a team of researchers who develop a robust method for the fabrication of highly uniform plasmonic magnetic microbeads (PMMBs) featured with metal nano-island coverage for the optimal plasmon-enhanced fluorescence, strong magnetism that allows efficient collection of beads, as well as varied sizes for multiplex detection of multiple targets simultaneously (Scheme 1).


The results appear in Analytical Chemistry by Dr Chao Yuan, Dr Zhidong Xiao, the associate Professors in College of Science; Professor Yunte Deng from Department of Pathology, Hubei Cancer Hospital; Dr Zhuang Liu, professor from Soochow University; and Xuemeng Li and Chengfei Li, two graduate students in Xiao Lab of Bioanalytes.

The research team in Xiao lab at HZAU

The synthetic route for PMMBs involves four steps, including surface modification of polystyrene (PS) microbeads, electrostatic adsorption of magnetic Fe3O4 nanoparticles (NPs), polydopamine (pDA) shell coating, and gold nanoparticles-induced silver nano-island membrane coating. It is worth mentioning that the multiple steps for PS microbeads coating are performed simply by solution reactions at room temperature, and could be easily scaled up. Owing to the highly uniform coverage of silver nano-island membrane on those magnetic microbeads, a high fluorescence enhancement factor of about 60-fold for fluorescein CF647 could be achieved. Compared with commercially available PS microbeads, our prepared PMMBs-based suspension array affords a broad dynamic range and improved detection sensitivity by approximately two orders of magnitude towards 100 fM for biomarker carcinoembryonic antigen (CEA). Importantly, the detection results obtained by our platform show excellent agreement with the clinic data for the detection of anti-acidic ribosomal phosphoprotein 0 (anti-P0) autoantibody in sera from systemic lupus erythematosus (SLE) patients. Finally, this PMMBs platform is expanded to multiplexed detection by using size-encode PMMBs for three biomarkers prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) with similar sensitivities.

“Our results collectively demonstrate the great promises of the magnetic PEF-based suspension array platform for bioassay with improved sensitivity in practical applications, we vision the promising application in the early diagnosis of cancer”, says Dr Xiao, the leading corresponding author of the research.

This work was supported by the National Basic Research Programs of China (2016YFA0201200), the Fundamental Research Funds for the Central Universities (2662016QD004, 2662017PY114), the National Natural Science Foundation of China (21705054), the Postdoctoral Science Foundation of China (2014M560443, 2015T80576), and the Collaborative Innovation Center of Soochow Nano Science and Technology.