On-chip droplet analysis and cell spheroid screening by capillary wrapping enabled shape-adaptive ferrofluid transporters.

Non-invasive droplet manipulation with no physical damage to the sample is important for the practical value of manipulation tools in multidisciplinary applications from biochemical analysis and diagnostics to cell engineering. It is a challenge to achieve this for most existing photothermal, electric stimuli, and magnetic field-based technologies. Herein, we present a droplet handling toolbox, the ferrofluid transporter, for non-invasive droplet manipulation in an oil environment. It involves the transport of droplets with high robustness and efficiency owing to low interfacial friction. This capability caters to various scenarios including droplets with varying components and solid cargo. Moreover, we fabricated a droplet array by transporter positioning and achieved droplet gating and sorting for complex manipulation in the droplet array. Benefiting from the ease of scale-up and high biocompatibility, the transporter-based droplet array can serve as a digital microfluidic platform for on-chip droplet-based bioanalysis, cell spheroid culture, and downstream drug screening tests.

A label-free immunosensor for the sensitive detection of hepatitis B e antigen based on PdCu tripod functionalized porous graphene nanoenzymes.

Nanomaterials with enzyme properties possess excellent catalytic activity and stability. We prepared new nanoenzymes to construct a label-free electrochemical immunosensor for the detection of hepatitis B e antigen (HBe Ag). In this study, PdCu tripod (PdCu TP) functionalized porous graphene (PG) nanoenzymes (PdCu TPs/PG) were prepared through the in situ reduction of PdCu tripods onto porous graphene. The catalytic Michaelis-Menten kinetic parameters of PdCu TPs/PG are better than horseradish peroxidase (HRP) and show enhanced peroxidase-like activity. Therefore, we used PdCu TPs/PG to catalyse the electrochemically active matrix of H2O2 and generate the synergistically amplified current signal for the subsequent sensitive detection of HBe Ag. Due to the good conductivity, large specific surface area and synergistic amplification of PdCu TPs/PG, the quantitative detection of HBe Ag shows a detection limit of 20 fg·mL-1 and linear range from 60 fg·mL-1 to 100 ng·mL-1. During the detection of human serum samples, PdCu TPs/PG shows good accuracy based on the standard addition method and a comparison with an ELISA. The prepared immunosensors exhibiting good selectivity, stability and reproducibility provide an important basis for determining the prognosis of hepatitis B and show potential applications in medical applications.

A Signal Amplification Strategy of CuPtRh CNB-Embedded Ammoniated Ti3C2 MXene for Detecting Cardiac Troponin I by a Sandwich-Type Electrochemical Immunosensor.

An early diagnosis of cardiovascular disease is of great importance to patients. Herein, a sandwich-type immunosensor for the detection of cardiac troponin I (cTnI) is prepared by using gold nanoparticles (Au NPs) and a composite (CuPtRh CNBs/NH2-Ti3C2) of trimetallic hollow CuPtRh cubic nanobox (CNB)-embedded few-layer ultrathin ammoniated MXene (NH2-Ti3C2). The embedding of the CuPtRh CNBs into NH2-Ti3C2 successfully prevents the restacking of NH2-Ti3C2 and offers more active sites for catalytic H2O2 reduction, which can effectively increase the current signal of the immunosensor. The designed sandwich-type electrochemical immunosensor for detection cTnI has a detection range of 25 fg mL-1 to 100 ng mL-1, and the detection limit is 8.3 fg mL-1 (S/N = 3). Moreover, the immunosensor also demonstrates high sensitivity, acceptable reproducibility, and good stability. More importantly, the designed system offers a direction for early clinical testing of cardiovascular and cerebrovascular diseases.

Amperometric immunoassay for the carcinoembryonic antigen by using a peroxidase mimic consisting of palladium nanospheres functionalized with glutathione-capped gold nanoparticles on graphene oxide.

A composite nanoenzyme was used in a sandwich-type electrochemical immunoassay for the carcinoembryonic antigen (CEA). Hierarchically porous palladium nanospheres (Pd NPs) were functionalized with glutathione-capped gold nanoparticles (G-Au NPs) and then loaded onto graphene oxide (GO) to obtain a peroxidase mimicking nanoenzyme of type GO-supported G-Au/Pd. The composite can catalyze the oxidation of the substrate tetramethylbenzidine (TMB) by H2O2 to give blue-colored oxidized TMB within only 20 s. This strong peroxidase activity, good conductivity and high specific surface area of the material make it a useful label for secondary antibodies (Ab2) for the detection of CEA. The cotton-like electrodeposited gold nanoparticles with good electrical conductivity were used to immobilize primary antibody (Ab1). The amperometric immunoassay has a detection range that extends from 10 fg·mL-1 to 100 ng·mL-1 at a working potential of -0.4 V with addition of 5 mmol·L-1 H2O2 as electrochemically active substrate, and the detection limit is as low as 3.2 fg·mL-1 (S/N = 3). Graphical abstract Schematic of sandwich electrochemical immunosensor for the carcinoembryonic antigen. Electrodeposited gold used as substrate material, and Graphene oxide supported G-Au NPs functionalized porous Pd nanospheres (GO supported G-Au/Pd) as signal amplification platform, which catalyze the oxidation of tetramethylbenzidine (TMB).

A label-free immunosensor based on PtPd NCs@MoS2 nanoenzymes for hepatitis B surface antigen detection.

Nowadays, nanomaterials with enzymatic properties have aroused wide interest because of their special advantages, such as catalytic activity, simple preparation method and high stability. We introduced new nanoenzymes to a label-free electrochemical immunosensor for Hepatitis B surface antigen (HBs Ag) detection. In this study, PtPd nanocubes@MoS2 nanoenzymes (PtPd NCs@MoS2) were prepared by loading PtPd nanocubes (PtPd NCs) on molybdenum disulfide nano-sheet (MoS2) through in situ redox polymerization. The prepared nanoenzymes exhibited enhanced peroxidase-like activity than separate MoS2 and PtPd NCs. The catalytic process of PtPd NCs@MoS2 is in agreement with the Michaelis-Menten kinetic equation. PtPd NCs@MoS2 were used for sensitive detection of HBs Ag, which is ascribed to their superior peroxidase activity, good conductivity and high specific surface area and synergistic amplification for current signals. Compared with the detection limit of colorimetric method (3.3 pg/mL), the electrochemical method (10.2 fg/mL) shows a lower detection limit and a wider linear range from 32 fg/mL to 100 ng/mL, so it is more suitable for quantitative analysis of Hepatitis B. In summary, the prepared immunosensor provides a better opportunity for early diagnosis of Hepatitis B and also has further applications in biosensing and medical diagnostics.

Sensitive amperometric immunosensor with improved electrocatalytic Au@Pd urchin-shaped nanostructures for human epididymis specific protein 4 antigen detection.

Sensitive detection of early ovarian cancer is imminent for women's health. Human epididymis specific protein 4 antigen (HE4 Ag), as a novel tumor marker, has good specificity and sensitivity in ovarian cancer markers, especially for the detection of early ovarian cancer. In this work, a novel and ultrasensitive sandwich-type amperometric electrochemical immunosensor was constructed using amine modified graphene supported gold nanorods (Au NRs/NH2-GS) as a sensor platform and core-shell Au@Pd urchin-shaped nanostructures (Au@Pd USs) as a label of the secondary antibodies (Ab2, Au@Pd USs-Ab2) to realize the quantitative determination of HE4 Ag. The Au NRs/NH2-GS were used for increasing the electrode surface area and effectively immobilizing primary antibodies (Ab1) due to its good water-solubility. The Au@Pd USs have special morphology with high crystal surface index and good stability, capable of loading secondary antibodies (Ab2) and providing a larger active site for the catalysis of hydrogen peroxide (H2O2). The proposed immunosensor displays excellent performance for HE4 Ag detection over the range from 1 pmol L-1 to 50 nmol L-1 with a detection limit of 0.33 pmol L-1 (signal-to-noise ratio of 3). Moreover, the designed immunosensor exhibits excellent reproducibility, selectivity, and stability, which shows great potential in clinical diagnosis.

Label-free immunosensors based on a novel multi-amplification signal strategy of TiO2-NGO/Au@Pd hetero-nanostructures.

A label-free electrochemical immunosensor for quantitative detection of human epididymis specific protein 4 antigen (HE4 Ag) was developed by a novel multi-amplification signal system. The multi-amplification signal system was formed by loading bimetallic Au@Pd holothurian-shaped nanoparticles (Au@Pd HSs) on titanium oxide nanoclusters functionalized nitrogen-doped reduced graphene oxide (TiO2-NGO). The Au@Pd HSs were obtained via seed-mediated approach with in-situ grown palladium nanoarms on gold nanorods (Au NRs) surfaces, which possessed good electrocatalysis for hydrogen peroxide (H2O2) reduction and excellent biocompatibility. The TiO2-NGO with the high catalytic activity and large specific surface area was synthesized by hydrothermal method. Using H2O2 as an electrochemically active substrate, the prepared label-free electrochemical immunosensor based on the TiO2-NGO/Au@Pd HSs hetero-nanostructures as the signal amplification platform exhibited excellent selectivity, reproducibility and stability for the detection of HE4 Ag. Meanwhile, the linear range from 40 fM to 60 nM with the detection limit of 13.33 fM (S/N = 3) was obtained, indicating the immunosensor offers a promising method for clinical detection of HE4 Ag.

A label-free electrochemical immunosensor based on the novel signal amplification system of AuPdCu ternary nanoparticles functionalized polymer nanospheres.

A sensitive label-free electrochemical immunosensor was designed using a novel signal amplification system for quantitative detecting hepatitis B surface antigen (HBsAg). Nitrogen-doped graphene quantum dots (N-GQDs) supported surfactant-free AuPdCu ternary nanoparticles (AuPdCu/N-GQDs), which featured with good conductivity and excellent catalytic properties for the reduction of hydrogen peroxide (H2O2), was synthesized by a simple and benign hydrothermal procedure. At the same time, the electroactive polymer nanospheres (PS) was synthesized by infinite coordination polymers of ferrocenedicarboxylic acid, which could play as carrier and electronic mediator to load AuPdCu/N-GQDs. The PS not only improved the ability to load antibodies because of the good biocompatibility, but also accelerated electron transport of the electrode interface attribute to plentiful ferrocene unit. Thus, the prepared AuPdCu/N-GQDs@PS has abilities of good biocompatibility, catalytic activity and electrical conductivity to be applied as transducing materials to amplify electrochemical signal in detection of HBsAg. Under optimal conditions, the fabricated immunosensor exhibited high sensitivity and stability in the detection of HBsAg. A linear relationship between current signals and the concentrations of HBsAg was obtained in the range from 10fg/mL to 50ng/mL and the detection limit of HBsAg was 3.3fg/mL (signal-to-noise ratio of 3). Moreover, the designed immunosensor with excellent selectivity, reproducibility and stability shows excellent performance in detection of human serum samples. Furthermore, this label-free electrochemical immunosensor has promising application in clinical diagnosis of HBsAg.