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Programmed death ligand 1 (PD-L1) exosomes are important biomarkers of immune activation in the initial stages of treatment and can predict clinical responses to PD-1 blockade in various cancer patients. However, traditional PD-L1 exosome bioassays face challenges such as high interface fouling in complex detection environments, limited detection specificity, and poor clinical serum applicability. Inspired by the multi-branched structure of trees, a biomimetic tree-like multifunctional antifouling peptide (TMAP)-assisted electrochemical sensor was developed for high-sensitivity exosomes detection. Multivalent interaction of TMAP significantly enhances the binding affinity of PD-L1 exosomes, thanks to the designed branch antifouling sequence, TMAPs antifouling performance is further improved. The addition of Zr4+ forms coordination bonds with the exosome's lipid bilayer phosphate groups to achieve highly selective and stable binding without interference from protein activity. The specific coordination between AgNCs and Zr4+ contributes to a dramatic change in the electrochemical signals, and lowing detection limit. The designed electrochemical sensor exhibited excellent selectivity and a wide dynamic response within the PD-L1 exosome concentration range from 78 to 7.8 × 107 particles/mL. Overall, the multivalent binding ability of TMAP and the signal amplification characteristics of AgNCs have a certain driving role in achieving clinical detection of exosomes. [ABSTRACT FROM AUTHOR]

Various tumor cells overexpress programmed death ligand 1 (PD-L1), a main immune checkpoint protein (ICP) embedded in the tumor cells membrane, to evade immune recognition through the interaction between PD-L1 and its receptor programmed death 1 (PD-1) which is from T-cells for maintaining immune tolerance. So inhibitors targeting the PD-1 or PD-L1 can block the PD-1/PD-L1 signaling pathway to restore the recognition activity of the immune system to tumor cells, which also have been utilized as a novel approach to improve the clinical therapeutic effect for cancer patients. Since not all cancer patients can respond to these inhibitors effectively, previous diagnosis of PD-L1 is significant to target the right treatments for cancer patients. This review pays attention to the PD-L1 detection and recent progress in the measurement of PD-L1 concentration, including various detection methods based on optical sensors as well as electrochemical assays. Apart from above those, we also focus on the prospects of PD-L1 detection in precision medicine. • A critical review of the detection for programmed death ligand 1 is presented. • Both current methods and emerging approaches are included. • The significance of accurate measurement of PD-L1 concentration for precision medicine is highlighted. • Challenges and future outlooks of detection for programmed death ligand 1 are presented. [ABSTRACT FROM AUTHOR]

Noble metal nanoparticles could provide a significant gain in sensitivity of surface plasmon resonance (SPR) sensor by electromagnetic field coupling between the localized plasmon resonance of nanoparticles and gold film. A facile and cost-effective SPR sensor based on magnetic field-aligned Fe 3 O 4 -coated silver magnetoplasmonic nanoparticles (Ag@MNPs) nanochain (M-Ag@MNPs) was proposed to improve the sensitivity of the sensor, which gave access to detect clinical targets at low concentration. Optimization experiments proved that 80 ng mL−1 M-Ag@MNPs-based SPR sensor showed high refractive index sensitivity and increased detection accuracy and quality factor when comparing with those of bare gold. Sialic acid binding Ig like lectins-15 (Siglec-15) was used as proof of concept to verify the sensitivity enhancement performance of M-Ag@MNPs in the actual detection process. SPR angle shifts of M-Ag@MNPs/gold sensor were significantly higher than those of traditional gold sensor under the same concentration of Siglec-15, which was consistent with previous performance analysis. Also, the detection limit of M-Ag@MNPs/gold sensor was calculated to be 1.36 pg mL−1. All these results had proved that aligning M-Ag@MNPs onto the gold chip could improve the performance of the SPR sensor and achieve sensitive detection of small amounts of clinical biomarkers. • A novel and facile biosensor based on M-Ag@MNPs was fabricated to detect Siglec-15 with low detection limit. • M-Ag@MNPs with enhanced electrochemical activities and SPR sensitivity was utilized. • The M-Ag@MNPs-based sensor provide a significant gain in RI S due to enhanced LSPR and high refractive index of Ag@MNPs. [ABSTRACT FROM AUTHOR]

Programmed death ligand 1 (PD-L1) immune checkpoint has been regarded as a new target for predicting cancer immunotherapy. As a transmembrane protein, PD-L1 has very low blood concentration and is likely to deplete their native activity when separated from the membrane environment due to significant hydrophobic domains, which make it difficult to measure sensitively. The reported PD-L1 aptamers and antibodies are both extracellular region binding molecules with the overlapping binding sites, which seriously limit with the construction of biosensor. Specific intracellular binding peptide (SIBP) as a unique PD-L1 intracellular region homing probe molecule is utilized for specifically capture targets. A simple and sensitive surface plasmon resonance (SPR) sandwich assay was constructed to detect serum soluble PD-L1 (sPD-L1) based on the unique and strong binding ability of SIBP to the intracellular region of sPD-L1. The designed SPR sensor showed great selectivity and wide dynamic response range of sPD-L1 concentration from 10 ng/mL to 2000 ng/mL. The limit of detection was calculated to be 1.749 ng/mL (S/N = 3). Owing to the SIBP's strong and specific binding ability with sPD-L1, the sensitive sensor can successfully detect sPD-L1 in serum samples, paving the way for the development of efficient test tools for clinical diagnosis and analysis. • A serum sensor was constructed based on the PD-L1 specific intracellular binding peptide (SIBP) which was proposed. • SIBP eliminates the steric interference of most PD-L1 immune binding molecules during sandwich sensor assembly. • The SPR sensor based on SIBP's robust binding force has excellent clinical detection capability. [ABSTRACT FROM AUTHOR]

This work presents a concept of "mass spectrometric biosensing" by using a chip to recognize the targets and mass spectrometry to detect the signals switched by the recognition. The chip is prepared on an ITO slide with a hydrophobic fluorous-tag monolayer to self-assemble the mixture of mass probe and fluorous-tagged cysteine as a spacer through fluorous affinity interaction. The presence of spacer provides suitable conditions for recognition reactions on the chip. By designing a single mass probe as the peptide substrates of corresponding target enzymes, a novel quantitative strategy based on the ratio of signal intensities of different species on the chip is developed for MALDI-MS assay of multiplex enzyme activities. Using caspase-3 and protein kinase A as targets, the reactions with designed mass probe produce three mass shifts to act as two "fingerprint" patterns for obtaining the dual enzyme activities. The proposed biosensing method shows the detectable ranges from 0.05 to 50 μU μL−1 and 0.4–40 μU μL−1 with correlation coefficients of 0.990 and 0.989 for PKA and caspase-3, respectively. The biosensing application has been demonstrated by monitoring these enzymes in cell lysates upon anti-cancer drug treatment, indicating the prospect of the novel biosensing protocol in biomedical study. • A concept of "mass spectrometric biosensing" is presented. • A chip is prepared with the designed single mass probe through fluorine-fluorine interaction. • A novel quantitative biosensing strategy based on the found "fingerprint" of MALDI mass spectrum is proposed. • A novel protocol for monitoring of multiplex enzyme activities in cell lysates is developed. [ABSTRACT FROM AUTHOR]