AIE-based superwettable microchips for evaporation and aggregation induced fluorescence enhancement biosensing.

Superwettable microchips with superhydrophilic microwells on superhydrophobic substrate have attracted increasing attention in fluorescence-based biological and medical diagnostics. However, traditional fluorophores often suffer from the aggregation-caused quenching (ACQ) problem at high concentration or in aggregated state. Here, we developed an AIE-based superwettable microchip by combining the evaporation-induced enrichment of superwettable microchips and the aggregation-induced emission of AIEgens together into one chip. Benefitting from the synergistic effect of the above two mechanisms, the AIE molecules (TPE-Z, a tetraphenylethene salt) were enriched from the diluted solution via evaporation and aggregated within the superhydrophilic microwell and then realized the fluorescence enhancement. Based on the dual enhancement effect of the AIE-based superwettable microchip, microRNA-141 (miR-141) can be detected with excellent reproducibility, sensitivity and specificity. A low detection limit of 1 pM can be achieved with higher signal-to-noise ratio than the traditional fluorescent probes. The proposed AIE-based superwettable microchip will provide a simple fluorescence enhancement biosensing platform for rapid, multiplexed and high-throughput analysis of specific targets in environmental monitoring, food safety, medical diagnosis and related research areas.

[1]  Hui Gao,et al.  Highly Efficient Far Red/Near-Infrared Solid Fluorophores: Aggregation-Induced Emission, Intramolecular Charge Transfer, Twisted Molecular Conformation, and Bioimaging Applications. , 2016, Angewandte Chemie.

[2]  Yongqiang Dong,et al.  Silole nanocrystals as novel biolabels. , 2004, Journal of immunological methods.

[3]  Doris Vollmer,et al.  Candle Soot as a Template for a Transparent Robust Superamphiphobic Coating , 2012, Science.

[4]  J. Homola,et al.  DNA-directed protein immobilization on mixed self-assembled monolayers via a streptavidin bridge. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[5]  B. Tang,et al.  AIE macromolecules: syntheses, structures and functionalities. , 2014, Chemical Society reviews.

[6]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[7]  Yanlin Song,et al.  Bio-inspired photonic-crystal microchip for fluorescent ultratrace detection. , 2014, Angewandte Chemie.

[8]  James R Heath,et al.  Microfluidics-based single-cell functional proteomics for fundamental and applied biomedical applications. , 2014, Annual review of analytical chemistry.

[9]  Kazuo Tanaka,et al.  Functionalization of boron diiminates with unique optical properties: multicolor tuning of crystallization-induced emission and introduction into the main chain of conjugated polymers. , 2014, Journal of the American Chemical Society.

[10]  Ben Zhong Tang,et al.  Lab in a Tube: Sensitive Detection of MicroRNAs in Urine Samples from Bladder Cancer Patients Using a Single-Label DNA Probe with AIEgens. , 2015, ACS applied materials & interfaces.

[11]  Huan H. Cao,et al.  Advancing Biocapture Substrates via Chemical Lift-Off Lithography , 2017 .

[12]  J. E. Mattson,et al.  A Group-IV Ferromagnetic Semiconductor: MnxGe1−x , 2002, Science.

[13]  Shutao Wang,et al.  A highly sensitive and facile graphene oxide-based nucleic acid probe: Label-free detection of telomerase activity in cancer patient's urine using AIEgens. , 2017, Biosensors & bioelectronics.

[14]  S. W. Thomas,et al.  Chemical sensors based on amplifying fluorescent conjugated polymers. , 2007, Chemical reviews.

[15]  B. Tang,et al.  Restriction of intramolecular motions: the general mechanism behind aggregation-induced emission. , 2014, Chemistry.

[16]  Ryan T. K. Kwok,et al.  Biosensing by luminogens with aggregation-induced emission characteristics. , 2015, Chemical Society reviews.

[17]  Robert Häner,et al.  Control of aggregation-induced emission by DNA hybridization. , 2013, Chemical communications.

[18]  Zhifang Fan,et al.  Sessile droplets for chemical and biological assays. , 2017, Lab on a chip.

[19]  Kai Song,et al.  Real-Time Fluorescence Detection in Aqueous Systems by Combined and Enhanced Photonic and Surface Effects in Patterned Hollow Sphere Colloidal Photonic Crystals. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[20]  L. Blum,et al.  DNA biosensors and microarrays. , 2008, Chemical reviews.

[21]  Subinoy Rana,et al.  Sensing of proteins in human serum using conjugates of nanoparticles and green fluorescent protein. , 2009, Nature chemistry.

[22]  Guanxin Zhang,et al.  Targeted bioimaging and photodynamic therapy of cancer cells with an activatable red fluorescent bioprobe. , 2014, Analytical chemistry.

[23]  H. Fuchs,et al.  In Situ Surface‐Modification‐Induced Superhydrophobic Patterns with Reversible Wettability and Adhesion , 2013, Advanced materials.

[24]  Myles Brown,et al.  The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. , 2009, Cancer research.

[25]  Xueji Zhang,et al.  Superwettable microchips with improved spot homogeneity toward sensitive biosensing. , 2018, Biosensors & bioelectronics.

[26]  Jia-rui Xu,et al.  Combined aggregation induced emission (AIE), photochromism and photoresponsive wettability in simple dichloro-substituted triphenylethylene derivatives† †Electronic supplementary information (ESI) available: Synthetic procedures, experimental details and supplemental figures. See DOI: 10.1039/c6sc01 , 2016, Chemical science.

[27]  Gao Yang,et al.  Ultratrace DNA Detection Based on the Condensing‐Enrichment Effect of Superwettable Microchips , 2015, Advanced materials.

[28]  Jing Chen,et al.  Hierarchical Porous Surface for Efficiently Controlling Microdroplets' Self‐Removal , 2013, Advanced materials.

[29]  Xiaoying Tang,et al.  A highly sensitive "turn-on" fluorescent probe with an aggregation-induced emission characteristic for quantitative detection of γ-globulin. , 2017, Biosensors & bioelectronics.

[30]  A. Woolley,et al.  Advances in microfluidic materials, functions, integration, and applications. , 2013, Chemical reviews.

[31]  Xingyu Jiang,et al.  Materials for Microfluidic Immunoassays: A Review , 2017, Advanced healthcare materials.

[32]  Lei Tao,et al.  Aggregation induced emission-based fluorescent nanoparticles: fabrication methodologies and biomedical applications. , 2014, Journal of materials chemistry. B.

[33]  C. Mirkin,et al.  Array-Based Electrical Detection of DNA with Nanoparticle Probes , 2002, Science.

[34]  D. Ding,et al.  Bioprobes based on AIE fluorogens. , 2013, Accounts of chemical research.

[35]  Hanchang Shi,et al.  Free-Energy-Driven Lock/Open Assembly-Based Optical DNA Sensor for Cancer-Related microRNA Detection with a Shortened Time-to-Result. , 2017, ACS applied materials & interfaces.

[36]  T. Dupont,et al.  Capillary flow as the cause of ring stains from dried liquid drops , 1997, Nature.

[37]  Burak Derkus,et al.  Applying the miniaturization technologies for biosensor design. , 2016, Biosensors & bioelectronics.

[38]  Ben Zhong Tang,et al.  Aggregation‐Induced Emission: The Whole Is More Brilliant than the Parts , 2014, Advanced materials.

[39]  Bai Yang,et al.  Fluorescent aptasensor based on aggregation-induced emission probe and graphene oxide. , 2014, Analytical chemistry.

[40]  B. Tang,et al.  Mitochondrial Imaging with Combined Fluorescence and Stimulated Raman Scattering Microscopy Using a Probe of the Aggregation-Induced Emission Characteristic. , 2017, Journal of the American Chemical Society.

[41]  Guoying Zhang,et al.  Highly selective fluorogenic multianalyte biosensors constructed via enzyme-catalyzed coupling and aggregation-induced emission. , 2014, Journal of the American Chemical Society.

[42]  Dmitry M Kolpashchikov,et al.  A binary DNA probe for highly specific nucleic Acid recognition. , 2006, Journal of the American Chemical Society.

[43]  H. Waldmann,et al.  Chemical strategies for generating protein biochips. , 2008, Angewandte Chemie.

[44]  D. Kolpashchikov,et al.  Four-way junction formation promoting ultrasensitive electrochemical detection of microRNA. , 2013, Analytical chemistry.

[45]  B. Tang,et al.  BSA-tetraphenylethene derivative conjugates with aggregation-induced emission properties: fluorescent probes for label-free and homogeneous detection of protease and α1-antitrypsin. , 2011, The Analyst.

[46]  Xiaohong Zhou,et al.  An Optical Biosensor-Based Quantification of the Microcystin Synthetase A Gene: Early Warning of Toxic Cyanobacterial Blooming. , 2018, Analytical chemistry.

[47]  Ryan T. K. Kwok,et al.  Aggregation-Induced Emission: Together We Shine, United We Soar! , 2015, Chemical reviews.

[48]  Yang Liu,et al.  Changing the Behavior of Chromophores from Aggregation‐Caused Quenching to Aggregation‐Induced Emission: Development of Highly Efficient Light Emitters in the Solid State , 2010, Advanced materials.

[49]  Mark Schena,et al.  Trends in microarray analysis , 2003, Nature Medicine.

[50]  Ben Zhong Tang,et al.  Real-Time, Quantitative Lighting-up Detection of Telomerase in Urines of Bladder Cancer Patients by AIEgens. , 2015, Analytical chemistry.

[51]  E. Wentzel,et al.  miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. , 2009, Cancer research.

[52]  Fang Zeng,et al.  A fluorescent assay for γ-glutamyltranspeptidase via aggregation induced emission and its applications in real samples. , 2016, Biosensors & bioelectronics.

[53]  David W Grainger,et al.  DNA and protein microarray printing on silicon nitride waveguide surfaces. , 2006, Biosensors & bioelectronics.

[54]  H. B. Halsall,et al.  Microfluidic immunosensor systems. , 2005, Biosensors & bioelectronics.

[55]  Shutao Wang,et al.  Superwettable Microchips as a Platform toward Microgravity Biosensing. , 2017, ACS nano.

[56]  A. Ludwig,et al.  High-Density Droplet Microarray of Individually Addressable Electrochemical Cells. , 2017, Analytical chemistry.

[57]  Ben Zhong Tang,et al.  Specific light-up bioprobes based on AIEgen conjugates. , 2015, Chemical Society reviews.

[58]  Jungmok Seo,et al.  Guided transport of water droplets on superhydrophobic-hydrophilic patterned Si nanowires. , 2011, ACS applied materials & interfaces.

[59]  P. Levkin,et al.  Emerging Applications of Superhydrophilic‐Superhydrophobic Micropatterns , 2013, Advanced materials.

[60]  S. Jenekhe,et al.  Excimers and Exciplexes of Conjugated Polymers , 1994, Science.

[61]  H S Kwok,et al.  Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. , 2001, Chemical communications.

[62]  W. Tao,et al.  Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation. , 2016, Journal of the American Chemical Society.