Rearranging Fluorescence-Magneto Spatialityfor “Win-Win” Dual Functions to Enhance Point-of-Care Diagnosis
Yu Su1, 2, Xirui Chen1, 2, Huan Huang4, 5, Yuhao Wu1, 2, Xuan-ang Shen1, 2, Xiangkai Lin1, 2, Kun Sun1, 2, Xiao-Yong Fan4, *, Xiaolin Huang1, 2, * and Yonghua Xiong1, 2, 3, *
[1] Dr. Y. Su, Dr. X. Chen, Y. Wu, X. Shen, X. Lin, K. Sun, Prof. X. Huang, Prof. Y. Xiong
State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
E-mail: xiaolin.huang@ncu.edu.cn; xiongyonghua@ncu.edu.cn
[2] Dr. Y. Su, Dr. X. Chen, Y. Wu, X. Shen, X. Lin, K. Sun, Prof. X. Huang, Prof. Y. Xiong
School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
[3] Prof. Y. Xiong
Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
H. Huang, Prof. X.-Y. Fan
Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China
E-mail: xyfan008@fudan.edu.cn
H. Huang
Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention, Department of Environmental Science & Engineering, Fudan University, Shanghai 200438, China
Keywords: fluorescent-magneto nanoemitters, aggregation-induced emission, self-assembly, point-of-care diagnosis, bacterial infection diagnosis
Abstract: Fluorescent-magneto nanoemitters have gained considerable attention for their applications in mechanical controlling-assisted optical signaling. However, the incompatibility between magnetic and fluorescent components often leads to functional limitations in traditional magneto@fluorescence nanostructure. Herein, we introduce a new compact-discrete spatial arrangement on a “fluorescence@magneto” core–shell nanostructure consisting of a close-packed aggregation-induced emission luminogen (AIEgen) core and a discrete magnetic shell. This structural design effectively eliminates the optical and magnetic interferences between the dual components by facilitating AIEgens loading in core region and reducing the magnetic feeding amount through effective exposure of the magnetic units. Thereby, the resulting magneto-AIEgen nanoparticle (MANP) demonstrates “win-win” performances: (i) high fluorescent intensity contributed by AIEgens stacking-enhanced photoluminescence and reduced photons loss from the meager magnetic shell; (ii) marked magnetic activity due to magneto extraposition-minimized magnetic shielding. Accordingly, the dual functions-retained MANP provides a proof of concept for construction of an immunochromatographic sensing platform, where it enables bright fluorescent labeling after magnetically enriching and separating procalcitonin and lipoarabinomannan in clinical human serum and urine, respectively, for the clinical diagnosis of bacterial infections-caused inflammation and tuberculosis. This study not only inspires the rational design of magnetic-fluorescent nanoemitter, but also highlights promising potential in magneto-assisted point-of-care test and biomedicine applications.
1. Introduction
The emergence of multifunctional materials (MFMs) that integrate multiple functions into a single hybrid has revolutionized nano-operation and expanded the range of applications.[1−4]Ideal MFMs should meet two main criteria: (i) maximize synthesis efficiency and minimize inactive components by adhering to the principle of “atom economy”, and (ii) achieve maximal integrated functionalities, known as “multifunctional efficiency”.[5,6] However, achieving excellent multiperformance in a single composite remains challenging due to the mismatch of physicochemical properties and mutual interferences among functional building blocks.[7,8]
Fluorescent-magneto nanoemitters (FMNs), as a typical type of MFM, combine luminous and magnetic properties, enabling brilliant optical signaling and mechanical magnetic manipulation. FMNs find widespread applications in sensing,[9−11]imaging,[12,13]biomedicine,[14,15] information decoding,[16] environmental treatment,[17,18] nanorobot operation[19,20] and catalysis.[21] Over the past decades, various synthesis strategies have been proposed for FMNs.[22−25] For example, a layer-by-layer assembly approach has been applied to synthesize FMNs by electrostatically attracting oppositely charged polyelectrolytes and CdTe quantum dots (QDs) on the surface of Fe3O4nanoparticles.[26] However, the weak binding affinity resulting from electrostatic interactions often leads to detachment of the exterior fluorescent particles from the FMNs. Another approach, introduced by Huang et al. , involves the chemical coupling of Fe3O4 core@silica shell@QDs satellites,[27] which improves colloid stability but compromises the loading capacity of fluorescent materials. In a remarkable advancement, Hu’s lab reported an affinity-driven assembly of Fe3O4 nanoparticles and QDs in radial dendritic silica colloids, achieving high packing density.[28] These developed MFMs exhibit a typical “magneto@fluorescence” core–shell structure, where the exterior QD layer causes severe magnetic shielding effects on the interior magnetic core.[29,30] Therefore, increasing the loading of magnetic units becomes necessary to maintain magnetic manipulation capability. However, excessive magnetic material loading can lead to fluorescent quenching due to the inner-filter effect (IFE) because the broad absorption of the magnetic component in the ultraviolet–visible (UV–vis) light region overlaps with the excitation and emission spectra of the existing fluorescent emitter.[31] In applications, such as lateral flow immunoassay (LFIA) detection, the mutual interference within FMNs poses a longstanding challenge. When a large amount of magnetic components stacks on a nitrocellulose (NC) membrane in the strip, it can cause nonlinear increments between the fluorescence signal and FMN content on the test and control line zones, thereby reducing the accuracy of the strip and potentially resulting in false negative results.
In theory, the rational spatial arrangement of FMNs with a novel “fluorescence@magneto” core–shell structure can effectively expose the magnetic units and reduce magnetic shielding, thereby decreasing the demand for magnetic loading and alleviating fluorescent IFE. Consequently, a worthy attempt is to decrease the exterior magneto loading while increasing the interior fluorophore content to achieve dual-retained activities. Moreover, ensuring a discrete spatial distribution of the magnetic layer is crucial to provide sufficient space for efficient photoluminescence process. Therefore, controlled phase separation in the nanometer regime through co-assembly becomes highly desirable.[32,33] For instance, in our previous work,[34] oleic acid-modified CdSe/ZnS QDs and Fe3O4 nanoparticles were successfully encapsulated into two polymer matrixes with different hydrophobic properties using a simple phase separation assembly. In this case, the magnetic and fluorescent components were mainly distributed in the outer layer, achieving a discrete co-display distribution that maintained high saturation magnetization due to the outward location of magnetic subunits. However, this approach sacrificed the large packing space inside the particle for fluorescent material because the maximized fluorophore coverage on the exterior interface was still not abundant enough to achieve a more enhanced fluorescent signal. Moreover, spatial separation of the two components is advantageous in minimizing multicomponent interference.[35] In addition, organic fluorescent emitters or inorganic fluorescent materials often suffer from the aggregation-caused quenching effect at high fluorophore concentrations or in the solid state, which hinders the enhancement of fluorescent brightness in compactly packed FMN hybrids.[36−38] By contrast, luminogens with aggregation-induced emission (AIEgens),[39,40]characterized by propeller-shaped structures, provide an excellent choice for remarkably increasing molecule loading and enhancing fluorescent intensity.
In this study, we present a novel compact-discrete “fluorescence@magneto” spatial arrangement by incorporating AIEgens into the core and hydrophobic Fe3O4 nanoparticles into the polymer shell (Scheme 1 ). This rational spatial design of the magneto-AIE nanoparticle (MANP) largely reduces magnetic shielding on the exterior magnetic shell, enabling a lower magnetic feeding amount. Consequently, the fluorescent performance is effectively maintained because of AIE-enhanced photoluminescence, a large AIEgen loading capacity, and reduced IFE by the meager magnetic shell. Capitalizing on the dual-retained magnetic and fluorescent properties, the MANP was employed as a bifunctional LFIA nanoprobe (MANP-LFIA) to magnetically enrich, separate, and fluorescently label procalcitonin (PCT) in serum samples and lipoarabinomannan (LAM) in urine samples of tuberculosis (TB) patients with remarkably enhanced sensitivity. We believe that the proposed MANP offers a new approach for the design of highly performing FMNs and holds great potential for applications in point-of-care test (POCT), fluorescent-magnetic resonance dual-mode imaging, and magnetically manipulated biomedicine.
Results and Discussion