Preparation of complex biological sample-compatible “turn-on”-type ratiometric fluorescent molecularly imprinted polymer microspheres via one-pot surface-initiated ATRP

Efficient Optosensing of Hippuric Acid in the Undiluted Human Urine with Hydrophilic “Turn-On”-Type Fluorescent Hollow Molecularly Imprinted Polymer Microparticles

“…H@NBD-MIP/CP@PEG were found to be uniform collapsed bowl-shaped microparticles with shrinked sizes (compared with their solid counterparts) in their dry state ( Figure 1 d,e), which again confirmed the successful removal of the silica core. DLS measurements also confirmed the successful synthesis of SiO 2 @NBD-MIP/CP@PEG with their hydrodynamic diameters ( D n,DLS ) larger than that of SiO 2 -Br (note that D n,DLS values are somewhat larger than D n,AFM values ( Table 1 ), as reported previously [ 19 , 21 ]). In addition, H@NBD-MIP/CP@PEG proved to have rather similar D n,DLS values as their solid counterparts in water, demonstrating that the hydrophilic hollow HA-MIP/CP microparticles have similar spherical morphologies as their solid counterparts in water.…”

“…To realize this goal, hydrophilic fluorescent hollow MIP microparticles (i.e., H@NBD-MIP@PEG, entry 4 in Table 1 ) were prepared through first one-pot synthesis of core-shell-corona-structured hydrophilic fluorescent solid MIP microspheres (i.e., SiO 2 @NBD-MIP@PEG, entry 2 in Table 1 ) and subsequent removal of their silica core via HF etching ( Scheme 1 ). SiO 2 @NBD-MIP@PEG microspheres were readily obtained via the controlled grafting of a NBD-labeled ultrathin HA-MIP layer with hydrophilic polymer brushes onto the preformed uniform “living” silica particles with surface-bound alkyl halide groups (i.e., ATRP-initiating groups) (prepared via one-pot sol-gel reaction of TEOS in the presence of BIBAPTES ( Scheme 1 b) [ 34 ]) via one-pot SI-ATRP in the presence of PEG-Br ( Scheme 1 b), where HA, 4-VP, MA-Urea-NBD, and EGDMA were utilized as the template, functional monomer, fluorescent comonomer, and cross-linker, respectively ( Scheme 1 b), according to our previous reports [ 17 , 18 , 19 ]. The carboxylic acid and amide groups of HA can form hydrogen bonding interactions with both the pyridine unit of 4-VP and ureido unit of MA-Urea-NBD, which can result in the formation of the self-assemblied HA/4-VP and HA/MA-Urea-NBD supramolecular complexes during the molecular imprinting process.…”

“…The hydrophilic fluorescent solid HA-MIP microspheres (i.e., SiO 2 @NBD-MIP@PEG) were prepared via one-pot SI-ATRP in the presence of a hydrophilic macro-ATRP initiator [i.e., PEG with one alkyl bromide end-group (or ATRP-initiating group) (PEG-Br)] with the “living” silica particles (SiO 2 -Br, entry 1 in Table 1 ) (see their preparation in the Supporting Information ) as the immobilized ATRP initiator following our previously reported procedure but with some modification (including the template and ratios of some reagents) [ 19 ]: 4-vinylpyridine (4-VP) (1.61 mmol), HA (0.81 mmol), MA-Urea-NBD (0.11 mmol), dried acetonitrile (70 mL), and methanol (24 mL) were added into a one-neck round-bottom flask (250 mL) with a magnetic stir bar inside successively. The self-assembly of the functional monomers and template was then carried out by first stirring the above solution in an ice-water bath for 2 h and then putting it in a refrigerator (4 °C) overnight.…”

“…To address the above-mentioned challenging issue, our group has developed some versatile strategies for preparing complex biological sample-compatible fluorescent MIPs through grafting hydrophilic polymer brushes onto the surfaces of the fluorescent MIP micro/nanoparticles (labeled with either an organic fluorescent unit or inorganic CdTe quantum dots (QDs) [ 14 , 15 , 16 ] or both of them [ 17 , 18 , 19 ]) via various controlled/“living” radical polymerization techniques. The resulting hydrophilic single fluorescent MIPs could directly and selectively detect antibiotic tetracycline (Tc) [ 14 , 16 ] and food additive folic acid (FA) [ 15 ] in the complex biological samples (including the undiluted pure serums [ 14 , 15 ] or both the undiluted pure serums and milks [ 16 ]) through fluorescence quenching (or “turn-off”) mechanism, while the obtained hydrophilic dual (or ratiometric) fluorescent MIPs were capable of directly and selectively optosensing (even with the naked eyes) the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in the undiluted pure milks through the fluorescence “turn-on” mechanism [ 17 , 18 , 19 ]. Note that the “turn-on”-type fluorescence of the optosensors can avoid false-positive responses owing to less interfering effects and achieve higher sensitivity due to their lower optical background and higher signal-to-noise ratio in comparison with fluorescence quenching [ 20 ].…”

“…Herein, we report on, for the first time, the development of complex biological sample-compatible “turn-on”-type fluorescent hollow MIP microparticles with enhanced optosensing performances by combining our recently developed one-pot surface-initiated atom transfer radical polymerization (ATRP) (SI-ATRP) strategy [ 19 ] and sacrificial template method. Hippuric acid (HA) was chosen here as the model target analyte because it is a major human metabolite in toluene-exposed humans (thus as an important biological indicator for occupational exposure monitoring) [ 32 ] and has also been recognized as a lung cancer biomarker in human plasma and urine samples [ 33 ].…”