High-sensitivity biosensor based on SERS integrated with dendrimer-assisted boronic acid-functionalized magnetic nanoparticles for IL-6 detection in human serum.

High-sensitivity quantitative analysis of sepsis disease markers in circulating blood is essential for sepsis early diagnosis, rapid stratification, and interventional treatment. Herein, a high-sensitivity biosensor combining surface-enhanced Raman spectroscopy (SERS) and functionalized magnetic materials was developed to quantitatively detect interleukin-6 (IL-6), a glycoprotein disease marker closely related to sepsis. First, boronic acid-functionalized magnetic nanomaterials with high adsorption performance were synthesized by utilizing the branched polyethyleneimine to provide many binding sites for boronic acid. Under antibody-free conditions, dendrimer-assisted boronic acid-functionalized magnetic nanomaterials selectively capture glycoproteins in complex biological samples as bio-capture element. Then, a core-shell bimetallic material with plenty of 'hot spots' was designed and synthesized as the enhancement substrate. The 4-Mercaptobenzonitrile (4-MP) with a characteristic peak at 2224 cm-1(Raman-silent region) was embedded as the Raman reporter to form a SERS immune probe with highly efficient electromagnetic enhancement effect, achieving specific recognition and high-sensitivity detection of IL-6 on bio-capture elements. Using this strategy for quantitative analysis of IL-6, a wide detection range (0.5-5000 pg ml-1) and a low detection limit (0.453 pg ml-1) were obtained. Moreover, this method exhibited excellent detection performance for IL-6 in human serum samples, demonstrating its potential promise in screening clinically relevant diseases. The biosensor presented here not only provides a novel and universally applicable sensing strategy for the enrichment and detection of trace glycoprotein disease markers, but also the application of a portable Raman spectrometer provides a more reliable experimental basis for the diagnosis and treatment of major diseases in the clinic or remote and deprived areas.

Integration of three non-interfering SERS probes combined with ConA-functionalized magnetic nanoparticles for extraction and detection of multiple foodborne pathogens.

A sandwich-structured SERS biosensor has been constructed for simultaneous detection of multiple pathogenic bacteria, consisting of non-interfering SERS probes for bacterial labeling and ConA-functionalizd magnetic nanoparticles for bacteria extraction. A the preparation method of PP3 SERS probe with high Raman activity is reported for the first time. Since the PP3 SERS probe has a very strong Raman peak at 2081 cm-1 in the "Raman silent region," the mixed SERS probe formed with MP1 and DP2 can meet the needs of multiple foodborne pathogen detection. Significantly, S. aureus, E. coli, and P. aeruginosa can be successfully extracted upon external magnetic field, and the limit of detection (LOD) is 1 CFU‧mL-1, lower than that of the congeneric detectors. This work paves a new way for the construction of a novel detector and absorbent for different bacteria in complex samples by using SERS probe.

Application progress of magnetic molecularly imprinted polymers chemical sensors in the detection of biomarkers.

Specific recognition and highly sensitive detection of biomarkers play an essential role in identification, early diagnosis and prevention of many diseases. Magnetic molecularly imprinted polymers (MMIPs) have been widely used to capture biomimetic receptors for targets in various complex matrices due to their superior recognition ability, structural stability, and rapid separation characteristics, which overcome the existing deficiencies of traditional recognition elements such as antibodies, aptamers. The integration of MMIPs as recognition elements with chemical sensors opens new opportunities for the development of advanced analytical devices with improved selectivity and sensitivity, shorter analysis time, and lower cost. Recently, MMIPs-chemical sensors (MMIPs-CS) have made significant progress in detection, but many challenges and development spaces remain. Therefore, this review focuses on the research progress of the sensor based on biomarker detection and introduces the surface modification of the magnetic support material used to prepare high selective MMIPs, as well as the selective extraction of target biomarkers by MMIPs from the complex biological sample matrix. Based on the understanding of optical sensors and electrochemical sensors, the applications of MMIPs-optical sensors (MMIPs-OS) and MMIPs-electrochemical sensors (MMIPs-ECS) for biomarker detection were reviewed and discussed in detail. Moreover, it provides an overview of the challenges in this research area and the potential strategies for the rational design of high-performance MMIPs-CS, accelerating the development of multifunctional MMIPs-CS.

Recent advancements in microfluidic chip biosensor detection of foodborne pathogenic bacteria: a review.

Foodborne diseases caused by pathogenic bacteria pose a serious threat to human health. Early and rapid detection of foodborne pathogens is an urgent task for preventing disease outbreaks. Microfluidic devices are simple, automatic, and portable miniaturized systems. Compared with traditional techniques, microfluidic devices have attracted much attention because of their high efficiency and convenience in the concentration and detection of foodborne pathogens. This article firstly reviews the bio-recognition elements integrated on microfluidic chips in recent years and the progress of microfluidic chip development for pathogen pretreatment. Furthermore, the research progress of microfluidic technology based on optical and electrochemical sensors for the detection of foodborne pathogenic bacteria is summarized and discussed. Finally, the future prospects for the application and challenges of microfluidic chips based on biosensors are presented.

Application of lectin-based biosensor technology in the detection of foodborne pathogenic bacteria: a review.

Foodborne diseases caused by pathogenic bacteria pose a serious threat to human health. Early and rapid detection of foodborne pathogens is urgently needed. The use of biosensors to identify and detect pathogenic bacteria has attracted ample attention because of their high sensitivity, near real-time quantification without enrichment, on-site detection, simple operation, and so on. As a promising alternative recognition element in biosensors, lectins have been widely studied in bacterial detection because of their high stability and low cost. In this review, we highlight the progress of lectin-based pathogen detection methods, including various electrochemical methods, optical methods and quartz crystal microbalance methods, as well as lectin based microfluidic methods. The interaction mechanism between lectins and bacterial recognition site-sugars is also studied. Finally, the future prospects and challenges in the development of lectin-based biosensors are discussed.

Simultaneous Quantitative Detection of IL-6 and PCT Using SERS magnetic immunoassay with sandwich structure.

Sepsis is a systemic inflammatory response syndrome caused by infection. The mortality rate is as high as 30%-50%. Early diagnosis and treatment can significantly improve the mortality of patients with sepsis. Therefore, we have developed a SERS-based magnetic immunoassay method that uses the principle of sandwich method to quantitatively detect Interleukin 6 (IL-6) and Procalcitonin (PCT). In this article, two different Raman reporter molecules are embedded in the middle of the Au@Ag shell and coupled with the tracer antibody to form a SERS immunoprobe. Biotin was coupled with capture antibody to form a sandwich structure when participating in the immune response. Streptavidin and biotin systems have extremely high binding affinity. The sandwich structure is quickly captured by SA magnetic beads and then applied with a magnetic field to enrich the magnetic beads. Finally, simultaneous quantitative detection is achieved by the intensity of the two Raman reporter characteristic peaks on the solution magnetic beads. IL-6 and PCT showed a good relationship between 0-1000 pg ml-1and 0-20 ng ml-1, respectively, and the limits of detection were 0.54 pg ml-1and 0.042 ng ml-1, respectively. The recovery rate was between 89.8% and 104.2%, both intra-assay and inter-assay CV were ≤20%. No cross-reaction with C-reactive protein (100µg ml-1), showing good specificity. This method provides a new technical reference for the clinical detection of sepsis biomarkers.

SERS-based boronate affinity biosensor with biomimetic specificity and versatility: Surface-imprinted magnetic polymers as recognition elements to detect glycoproteins.

Glycoproteins are a class of proteins with significant biological functions and clinical implications. Due to glycoproteins' reliability for the quantitative analysis, they have been used as biomarkers and therapeutic targets for disease diagnosis. We propose a sandwich structure-based boronate affinity biosensor that can separate and detect target glycoproteins by magnetic separation and Surface-enhanced Raman scattering (SERS) probes. The biosensor relies on boronic acid affinity magnetic molecularly imprinted polymer (MMIPs) with pH response as "capturing probe" for glycoproteins, and Au-MPBA@Ag modified with 4-mercaptophenylboronic acid (MPBA) as SERS probes, among which, MPBA has both strong SERS activity and can specifically recognize and bind to glycoproteins. MMIPs ensured specific and rapid analysis, and SERS detection provided high sensitivity. The proposed boronate affinity SERS strategy exhibited universal applicability and provided high sensitivity with limit of detection of 0.053 ng/mL and 0.078 ng/mL for horseradish peroxidase and acid phosphatase, respectively. Ultimately, the boronate affinity SERS strategy was successfully applied in detection of glycoprotein in spiked serum sample with recovery between 90.6% and 103.4%, respectively. In addition, this study used a portable Raman meter, which can meet the requirements of point-of-care testing. The biosensor presented here also has advantages in terms of cost-effectiveness, stability, and detection speed.

SERS-based magnetic immunoassay for simultaneous detection of cTnI and H-FABP using core-shell nanotags.

Acute myocardial infarction (AMI) is the single leading cause of worldwide mortality and morbidity. Heart-type fatty acid-binding protein (H-FABP) and cardiac troponin I (cTnI), as biomarkers emerging at different stages of AMI, have complementary advantages in terms of specificity and sensitivity. Therefore, we developed a magnetic immunoassay method based on surface-enhanced Raman scattering (SERS) to detect H-FABP and cTnI simultaneously. Herein, two mutually independent Raman reporter molecules were embedded between a gold core and silver shell and then combined with a tracer antibody to form a SERS immunoprobe. During detection, the SERS immunoprobe, target antigen and capture probe undergo an immune reaction to form a sandwich structure, and then the immune complex was enriched by a specific reaction of streptavidin on the surface of magnetic beads with biotin. Finally, the concentration of biomarkers was quantified by detecting the characteristic Raman peak intensities of the two Raman reporter molecules. Under the optimized conditions, the minimum detection limits of H-FABP and cTnI were 0.6396 and 0.0044 ng mL-1, respectively. Besides, the target antigen does not cross-react with non-specific proteins, showing good specificity. Therefore, our proposed SERS-based magnetic immunoassay method has the advantages of accuracy, rapidity and good selectivity, and has great potential for early diagnosis of acute myocardial infarction disease.