Design Of Functionalized Metal-organic Framework Composites And Their Biosensing Applications

Metal-organic frameworks（MOFs）,a class of porous hybrid materials composed of metal/clusters and organic ligands,have large specific surface area,excellent stability,and regular adjustable pore size.MOFs materials can achieve performance optimization and expansion by rational functional design and modification of metal centers,functional groups connected by organic ligands,and pore space,showing great application potential in the field of biosensors.Especially in the immobilization of biomolecules,the transduction/amplification of electrical signals and the output of optical signals,functionalized MOFs exhibited excellent performance.In this thesis,we designed and synthesized four types of novel functionalized MOFs materials,and studied their biological recognition,catalytic efficiency,luminescence intensity and conductivity,and explored their biosensing mechanisms.Combined with efficient signal amplification strategies,such as enzyme-like catalysis,antibody directional immobilization,energy transfer,etc.,a series of simple,rapid and sensitive electrochemical/electrochemiluminescence biosensors were constructed to achieve highly sensitive detection of disease markers calcitonin（PCT）,neuron-specific enolase（NSE）and carbohydrate antigen（CA242）,which is of great significance in the early detection and diagnosis of diseases.The main research contents are as follows:（1）Highly conductive Au/IRMOF material based electrochemical biosensor for the detection of calcitonin（PCT）.NH₂-IRMOF-3 were synthesized with Zn²⁺as the metal node and diamino terephthalic acid（NH₂-H₂BDC）as the organic ligand.Amino-modified NH₂-IRMOF-3 can use stable chemical bonds to load Au nanoparticles（NPs）on the surface to form Au/IRMOF-3 composites.The biosensing interface constructed by Au/IRMOF-3 as a substrate material not only effectively increased the amount of capture antibody（Ab₁）,but also accelerated the electron transfer rate at the electrode interface and improved the sensitivity of the biosensor.The sea cucumber-like trimetallic nanorods（Pd@Pt Rh SNRs）with unique hierarchical structure showed excellent catalytic ability.Hydroquinone（HQ）was used as an electronic medium to achieve dual electrochemical signal output,enabling the biosensor to obtain self-calibration capabilities and improve detection accuracy.The constructed dual-signal electrochemical biosensor achieved sensitive analysis and detection of the sepsis marker PCT with excellent stability and selectivity.The linear range reached 20 fg/m L～100ng/m L,and was successfully used for the detection of PCT in human serum.（2）Electroactive mixed-valence Fe-MOF based electrochemical biosensor for the detection of neuron-specific enolase（NSE）.The electroactive Fe²⁺/Fe³⁺-MOF was synthesized by selecting NH₂-H₂BDC organic ligand and introducing Fe²⁺metal nodes with high energy electrons by vacuum heating to promote charge transfer.The infinite one-dimensional Fe-O-Fe chain andπ-conjugated system of Fe²⁺/Fe³⁺-MOF structure achieved long-range charge delocalization,which greatly improved its conductivity and mobility.The presence of active site Fe²⁺improved the catalytic efficiency of Fe²⁺/Fe³⁺-MOF,the current response was further enhanced,and can directly realize the dual output of electrochemical signals without introducing other electronic media.The MoS₂nanoflower（NFs）as a cocatalyst ensured a stable cycle of Fe²⁺/Fe³⁺at the electrode interface,and provided a dual enhancement effect on the improvement of the current response.The label-free dual-signal electrochemical biosensor based on Au-MoS₂/MOF achieved sensitive self-calibration detection of lung cancer marker NSE,demonstrating excellent analytical performance and actual sample detection ability.The linear range was 1.00～100 ng/m L,and the detection limit was 0.37 pg/m L（i-t）and 0.52 pg/m L（SWV）.（3）Self-enhanced luminescent mixed ligand Eu-MOF based electrochemiluminescence biosensor for the detection of carbohydrate antigen（CA242）.The self-luminous enhanced mixed ligand Eu-MOF was synthesized,in which the luminescent lanthanide ion Eu³⁺was selected as the metal node,NH₂-H₂BDC as the organic ligand,and 1,10-phenanthroline（Phen）was designed as the second ligand.The introduction of Phen adjusted the energy gap between the lowest triplet state of the organic ligand and the excited state of Eu³⁺,enhanced the“antenna effect”,and further improved the luminous efficiency of Eu-MOF.Under the optimal ratio of mixed ligands,Eu-MOF obtained efficient and stable ECL performance at low excitation potential（0.83V）.FeCo@CNT with strong electrocatalytic activity as a co-reaction promoter accelerated the generation of strong reducing radicals of co-reactant（TPr A）.Combined with the high affinity of peptide residues（HWRGWVC）to antibodies,we proposed an antibody-oriented modified FeCo@CNT-HWR biosensor matrix interface,which effectively improved the construction efficiency and specificity of the sensor.The constructed ECL self-enhanced biosensor can achieve rapid and sensitive detection of the pancreatic cancer marker CA242 with a wide linear range（0.005 U/m L～100 U/m L）and a low detection limit（0.0019 U/m L）.（4）Host-guest promoted luminescence Tb³⁺doped Ce-MOF based electrochemiluminescence biosensor for the detection of CA242.A host-guest induced enhanced ECL multifunctional Tb³⁺@Ce³⁺/Ce⁴⁺-MOF was synthesized by selecting mixed valence Ce³⁺/Ce⁴⁺-MOF as the host framework and introducing luminescent lanthanide ion Tb³⁺as the guest.The multifunctional host framework Ce³⁺/Ce⁴⁺-MOF can not only use Ce³⁺and H₂BPy DC to double sensitize the luminescence of Tb³⁺,but also act as a short-range co-reaction promoter to accelerate the conversion of co-reaction reagent S₂O₈^2-to SO₄^·-by active electrons of Ce³⁺/Ce⁴⁺,which improves the overall reaction rate of ECL and effectively improves the luminescence efficiency.Through Au-S bond,HWRGWVC was conjugated with hollow urchin-like Cu₂O@Au to increase the specificity of the interface to antigens.At the same time,Cu⁺in Cu₂O@Au increased the number of SO₄^·-radicals produced by electrochemistry and further enhanced the ECL emission intensity.The electrochemical luminescence biosensor based on Tb³⁺@Ce-MOF as a signal probe realized the highly sensitive detection of CA242 with a linear range of 0.001 U/m L～100 U/m L and a detection limit as low as 0.00052 U/m L.