Bioresponsive Release System for Visual Fluorescence Detection of Carcinoembryonic Antigen from Mesoporous Silica Nanocontainers Mediated Optical Color on Quantum Dot-Enzyme-Impregnated Paper.

An all-in-one paper-based analytical device (PAD) was successfully developed for visual fluorescence detection of carcinoembryonic antigen (CEA) on CdTe/CdSe quantum dot (QD)-enzyme-impregnated paper by coupling with a bioresponsive controlled-release system from DNA-gated mesoporous silica nanocontainers (MSNs). The assay was carried out in a centrifuge tube by using glucose-loaded MSNs with a CEA aptamer and a QD-enzyme-paper attached on the lid. Initially, single-strand complementary DNA to a CEA aptamer was covalently conjugated to the aminated MSN, and then glucose (enzyme substrate) molecules were gated into the pore with the help of the aptamer. Glucose oxidase (GOD) and CdTe/CdSe QDs were coimmobilized on paper for the visual fluorescence signal output. Upon target CEA introduction in the detection cell, the analyte specifically reacted with the immobilized aptamer on the MSN to open the pore, thereby resulting in the glucose release. The released glucose was oxidized by the immobilized GOD on paper to produce gluconic acid and hydrogen peroxide, and the latter quenched the fluorescence of CdTe/CdSe QDs, which could be determined by the naked eye on a portable smartphone and a commercial fluorospectrometer. Under optimal conditions, the PAD-based sensing system enabled sensitive discrimination of target CEA against other biomarkers or proteins in a linear range of 0.05-20 ng mL-1 with a limit of detection of 6.7 pg mL-1 (ppt). In addition, our strategy displayed high specificity, good reproducibility, and acceptable accuracy for analyzing human serum specimens with a commercial human CEA ELISA kit. Importantly, this methodology offers promise for simple analysis of biological samples and is suitable for use in the mass production of miniaturized devices, thus opening new opportunities for protein diagnostics and biosecurity.

[1]  Steve Feng,et al.  Cellphone-Based Hand-Held Microplate Reader for Point-of-Care Testing of Enzyme-Linked Immunosorbent Assays. , 2015, ACS nano.

[2]  I. Willner,et al.  Dual switchable CRET-induced luminescence of CdSe/ZnS quantum dots (QDs) by the hemin/G-quadruplex-bridged aggregation and deaggregation of two-sized QDs. , 2014, Nano letters.

[3]  George M Whitesides,et al.  Electrochemical sensing in paper-based microfluidic devices. , 2010, Lab on a chip.

[4]  Yufang Zhu,et al.  DNA-capped Fe3O4/SiO2 magnetic mesoporous silica nanoparticles for potential controlled drug release and hyperthermia , 2015 .

[5]  N. Jana,et al.  β-Cyclodextrin functionalized magnetic mesoporous silica colloid for cholesterol separation. , 2015, ACS applied materials & interfaces.

[6]  Martti Toivakka,et al.  Paper-based microfluidics: fabrication technique and dynamics of capillary-driven surface flow. , 2014, ACS applied materials & interfaces.

[7]  Dafu Cui,et al.  A hard-soft microfluidic-based biosensor flow cell for SPR imaging application. , 2010, Biosensors & bioelectronics.

[8]  Weihong Tan,et al.  DNA-capped mesoporous silica nanoparticles as an ion-responsive release system to determine the presence of mercury in aqueous solutions. , 2012, Analytical chemistry.

[9]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[10]  Jinghua Yu,et al.  Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. , 2012, Biomaterials.

[11]  D. Sinton,et al.  Direct DNA Analysis with Paper-Based Ion Concentration Polarization. , 2015, Journal of the American Chemical Society.

[12]  J. L. Delaney,et al.  Electrogenerated chemiluminescence detection in paper-based microfluidic sensors. , 2011, Analytical chemistry.

[13]  L. J. Mueller,et al.  pH-responsive nanogated ensemble based on gold-capped mesoporous silica through an acid-labile acetal linker. , 2010, Journal of the American Chemical Society.

[14]  Brian G. Trewyn,et al.  Mesoporous Silica Nanoparticles for Drug Delivery and Biosensing Applications , 2007 .

[15]  G. Whitesides,et al.  Diagnostics for the developing world: microfluidic paper-based analytical devices. , 2010, Analytical chemistry.

[16]  James F Rusling,et al.  Electrochemiluminescence at Bare and DNA-Coated Graphite Electrodes in 3D-Printed Fluidic Devices. , 2016, ACS sensors.

[17]  R. Yolken,et al.  Enzyme-linked immunosorbent assay for identification of rotaviruses from different animal species. , 1978, Science.

[18]  Zhenxin Wang,et al.  Sensitive Detection of Polynucleotide Kinase Activity by Paper-Based Fluorescence Assay with λ Exonuclease Assistance. , 2016, Analytical chemistry.

[19]  Detlev Belder,et al.  Microfluidic chips for chirality exploration. , 2011, Analytical chemistry.

[20]  Tony Jun Huang,et al.  Microfluidic diagnostics for the developing world. , 2012, Lab on a chip.

[21]  U. Maitra,et al.  Supramolecular Approach to Enzyme Sensing on Paper Discs Using Lanthanide Photoluminescence , 2016 .

[22]  Ulrich J. Krull,et al.  Paper-based solid-phase nucleic acid hybridization assay using immobilized quantum dots as donors in fluorescence resonance energy transfer. , 2013, Analytical chemistry.

[23]  G. Crespo,et al.  A low-cost thin layer coulometric microfluidic device based on an ion-selective membrane for calcium determination. , 2014, The Analyst.

[24]  Nikolai Gaponik,et al.  Application of polymer quantum dot-enzyme hybrids in the biosensor development and test paper fabrication. , 2012, Analytical chemistry.

[25]  Jie Xu,et al.  Detection of heavy metal by paper-based microfluidics. , 2016, Biosensors & bioelectronics.

[26]  J. Qin,et al.  A high efficiency microfluidic-based photocatalytic microreactor using electrospun nanofibrous TiO2 as a photocatalyst. , 2013, Nanoscale.

[27]  Jun-Jie Zhu,et al.  DNA-hybrid-gated multifunctional mesoporous silica nanocarriers for dual-targeted and microRNA-responsive controlled drug delivery. , 2014, Angewandte Chemie.

[28]  Kin Fong Lei,et al.  Paper-based enzyme-free immunoassay for rapid detection and subtyping of influenza A H1N1 and H3N2 viruses. , 2015, Analytica chimica acta.

[29]  Won Suk Chang,et al.  Electrodeposition-based 3D Printing of Metallic Microarchitectures with Controlled Internal Structures. , 2015, Small.

[30]  Yi Lin,et al.  One-step separation-free detection of carcinoembryonic antigen in whole serum: Combination of two-photon excitation fluorescence and optical trapping. , 2017, Biosensors & bioelectronics.

[31]  Ulrich J Krull,et al.  Paper-based solid-phase multiplexed nucleic acid hybridization assay with tunable dynamic range using immobilized quantum dots as donors in fluorescence resonance energy transfer. , 2013, Analytical chemistry.

[32]  Matt Trau,et al.  Field Demonstration of a Multiplexed Point-of-Care Diagnostic Platform for Plant Pathogens. , 2016, Analytical chemistry.

[33]  Bingling Li,et al.  DNA detection using origami paper analytical devices. , 2013, Analytical chemistry.

[34]  Itamar Willner,et al.  Optical molecular sensing with semiconductor quantum dots (QDs). , 2012, Chemical Society reviews.

[35]  Victor S-Y Lin,et al.  A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. , 2003, Journal of the American Chemical Society.

[36]  C. Brosseau,et al.  Development of a SERS-Based Rapid Vertical Flow Assay for Point-of-Care Diagnostics. , 2017, Analytical chemistry.

[37]  Xinhao Wang,et al.  White blood cell counting on smartphone paper electrochemical sensor. , 2017, Biosensors & bioelectronics.

[38]  Ruth M Barnard,et al.  Flow cytometry: a flexible tool for biomarker research. , 2012, Bioanalysis.

[39]  Shuming Nie,et al.  Semiconductor nanocrystals: structure, properties, and band gap engineering. , 2010, Accounts of chemical research.

[40]  Zhong-yuan Lu,et al.  Controllable synthesis of hollow mesoporous silica particles by a facile one-pot sol-gel method. , 2015, Chemical communications.

[41]  Robin L. Jones,et al.  The spectrum of EWSR1-rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities , 2017, British Journal of Cancer.

[42]  Zhenli Qiu,et al.  CdTe/CdSe quantum dot-based fluorescent aptasensor with hemin/G-quadruplex DNzyme for sensitive detection of lysozyme using rolling circle amplification and strand hybridization. , 2017, Biosensors & bioelectronics.

[43]  Yu Xiang,et al.  Integration of Solution-Based Assays onto Lateral Flow Device for One-Step Quantitative Point-of-Care Diagnostics Using Personal Glucose Meter , 2016 .

[44]  David R. Liu,et al.  Analytical Devices Based on Direct Synthesis of DNA on Paper. , 2016, Analytical chemistry.

[45]  Dana M Spence,et al.  Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular Adherence Prior to Electrical Lysis. , 2015, Analytical chemistry.

[46]  Xiaoxi Yang,et al.  Quantitative, Point-of-Care Immunoassay Platform to Guide and Monitor Sickle Cell Disease Therapy. , 2016, Analytical chemistry.

[47]  Ren Sun,et al.  Genetic analysis of H1N1 influenza virus from throat swab samples in a microfluidic system for point-of-care diagnostics. , 2011, Journal of the American Chemical Society.

[48]  Wenwen Jing,et al.  Microfluidic device for efficient airborne bacteria capture and enrichment. , 2013, Analytical chemistry.

[49]  Haoting Lu,et al.  H2O2-sensitive quantum dots for the label-free detection of glucose. , 2010, Talanta.