Functionalization Of Magnetic Nanoparticles And Its Application In The Detection Of Disease Markers

In recent years,magnetic nanoparticles(MNPs)with superparamagnetic properties have been widely used in drug targeting,cell separation,DNA and protein separation and detection,etc.,and MNPs with specific physical and chemical properties and surface functions show excellent rapid responsiveness,directional capture ability to target and signal amplification.Therefore,the functionalization of MNPs has attracted much attention in the field of biosensor research and development.Functionalized MNPs can combine identification,signal output,separation and enrichment into the transducer material or dispersed in the sample,and then attract it to the detection surface of the sensor by external magnetic field to enhance the sensitivity and stability,showing excellent clinical application prospects in detecting disease markers.Based on this,two kinds of functionalized MNPs complexes are synthesized in this paper.Combined with surface plasmon resonance(SPR)and electrochemical methods,the signal output is accurate and fast,and sensors for biomarkers of heart failure and immunodeficiency diseases are constructed respectively.The practical application performance of the immunoassay is evaluated.The main research contents of this paper are as follows: 1.Analyte-resolved magnetoplasmonic nanocomposite to enhance SPR signals and dual recognition strategy for detection of BNP in serum samplesB-type natriuretic peptide(BNP)is a short peptide that is considered to be an important heart failure(HF)related biomarker.Due to its low concentration in the blood and short half-life,the sensitive detection of BNP is a bottleneck for diagnosing patients at early stages of HF.In this chapter,we report a surface plasmon resonance(SPR)sensor based on functionalized MNPs to measure BNP;the sensor is based on aptamer-functionalized gold nanoparticles(GNPs-Apt)and antibody-modified magnetic nanoparticles(MNPs-Ab)to enable dual screening of BNP in complex environments.In the detection system,BNP forms MNPs-Ab/BNP/GNP-Apt magnetic plasma nanoconjugates that can be rapidly separated from the complex sample by an external magnetic field,thereby avoiding degradation of the analyte during the half-life period.At the same time,this magnetic plasma nanocomposite can enhance SPR signal.The developed SPR biosensor shows high selectivity,a wide dynamic response range of BNP concentrations from 100 fg/m L to 10 ng/m L,and a low detection limit of 28.2 fg/m L(S/N=3).Using the proposed sensor,BNP was successfully detected in clinical samples.Thus,the designed SPR biosensor in this chapter provides a novel and sensitive sensing method for BNP detection with potential applications in clinical practice.2.Natural receptor-based competitive immunoelectrochemical assay for ultra-sensitive detection of Siglec 15Sialic acid-binding immunoglobulin-like lectin 15(Siglec 15)is a novel immunomodulatory target and was identified as an immune suppressor in the tumor microenvironment.Accurate assessment of Siglec 15 expression levels is critical for cancer prognosis and treatment.In this chapter,in order to simulate the interaction between Siglec 15 and DNAX-activating protein(DAP 12)in cell signaling pathways,immunoelectrochemical sensors based on functionalized MNPs and natural receptors were designed.Siglec 15 modified on the electrode surface specifically recognizes and binds ferrocene(Fc)-labeled DAP 12,and uses it as an electrochemical signal reporter.Antibody-functionalized MNPs recognize and enrich Siglec 15 in a complex detection system and direct the target to the sensor surface under the action of an external magnetic field.The free Anti-Siglec 15 will "squeeze out" the DAP 12-Fc and bind to the Siglec 15 on the electrode surface.The concentration of Siglec 15 in the final sample is positively correlated with the change in electrochemical signal.Natural receptor-based competitive assay ensures the efficient binding between antibody and Siglec 15 and decrease the nonspecific interaction.The rapid enrichment and directional capture capabilities of functional MNPs ensure the high sensitivity and selectivity of this competitive assay.Therefore,this simple electrochemical sensor based on functionalized MNPs and natural receptors has certain potential in practical clinical applications.