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Sensing of viral antigens has become a critical tool in combating infectious diseases. Current sensing techniques have a tradeoff between sensitivity and time of detection; with 10–30 min of detection time at a relatively low sensitivity and 6–12 h of detection at a high (picomolar) sensitivity. In this research, uniquely nanoengineered interfaces are demonstrated on 3D electrodes that enable the detection of spike antigens of SARS‐CoV‐2 and their variants in seconds at femtomolar concentrations with excellent specificity, thus, overcoming this tradeoff. The 3D electrodes, manufactured using a high‐resolution aerosol jet 3D nanoprinter, consist of a microelectrode array of sintered gold nanoparticles coated with graphene and antibodies specific to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) spike antigens. An impedance‐based sensing modality is employed to sense several pseudoviruses of SARS‐CoV‐2 variants of concern (VOCs). This device is sensitive to most of the pseudoviruses of SARS‐CoV‐2 VOCs. A high sensitivity of 100 fm, along with a low limit‐of‐detection of 9.2 fmwithin a test range of 0.1–1000 pm, and a detection time of 43 s are shown. This work illustrates that effective nano‐bioengineering of interfaces can be used to create an ultrafast and ultrasensitive healthcare diagnostic tool for combating emerging infections.

 

Abstract Sensing of clinically relevant biomolecules such as neurotransmitters at low concentrations can enable an early detection and treatment of a range of diseases. Several nanostructures are being explored by researchers to detect biomolecules at sensitivities beyond the picomolar range. It is recognized, however, that nanostructuring of surfaces alone is not sufficient to enhance sensor sensitivities down to the femtomolar level. In this paper, we break this barrier/limit by introducing a sensing platform that uses a multi-length-scale electrode architecture consisting of 3D printed silver micropillars decorated with graphene nanoflakes and use it to demonstrate the detection of dopamine at a limit-of-detection of 500 attomoles. The graphene provides a high surface area at nanoscale, while micropillar array accelerates the interaction of diffusing analyte molecules with the electrode at low concentrations. The hierarchical electrode architecture introduced in this work opens the possibility of detecting biomolecules at ultralow concentrations. 

The rapid growth of point-of-care tests demands for biomolecule sensors with higher sensitivity and smaller size. We developed an optofluidic metasurface that combined silicon photonics and nanofluidics to achieve a lateral flow-through biosensor to fulfill the needs. The metasurface consists of a 2D array of silicon nanoposts fabricated on a silicon-on-insulator substrate. The device takes advantage of the high-Q resonant modes associated with the optical bound state and the nanofluidic delivery of analyte to overcome the problem of diffusion-limited detection that occurs in almost all conventional biosensors and offer a high refractive index sensitivity. We used rigorous coupled wave analysis and finite element analysis to design and optimize the device. We will present its photonic band diagram to identify the optical bound state and high-Q resonance modes near 1550 nm. The device was fabricated using e-beam lithography followed by a lift-off and reactive ion etching process. Reflectance of the sensor was measured using a tunable laser and a photodetector. The preliminary result shows a refractive index sensitivity of 720 nm/RIU. Furthermore, we implemented the optical metasurface as a lateral flow-through biosensor by covering the nanoposts using a PDMS cover. The nanofluidic channels are formed between the nanoposts for the flow of samples. The lateral flow-through sensor was used to detect the epidermal growth factor receptor (ErbB2), a widely used protein biomarker for breast cancer screening. The results show that the device can quantitatively measure the binding of ErBb2 antibody and ErBb2 by the continuous monitoring of the resonant wavelength shift. 

This paper reports an integrated dual-modality microfluidic sensor chip, consisting of a patterned periodic array of nanoposts coated with gold (Au) and graphene oxide (GO), to detect target biomarker molecules in a limited sample volume. The device generates both electrochemical and surface plasmon resonance (SPR) signals from a single sensing area of Au–GO nanoposts. The Au–GO nanoposts are functionalized with specific receptor molecules, serving as a spatially well-defined nanostructured working electrode for electrochemical sensing, as well as a nanostructured plasmonic crystal for SPR-based sensing via the excitation of surface plasmon polaritons. High sensitivity of the electrochemical measurement originates from the presence of the nanoposts on the surface of the working electrode where radial diffusion of redox species occurs. Complementarily, the SPR detection allows convenient tracking of dynamic antigen–antibody interactions, to describe the association and dissociation phases occurring at the sensor surface. The soft-lithographically formed nanoposts provide high reproducibility of the sensor response to epidermal growth factor receptor ( ErbB2 ) molecules even at a femtomolar level. Sensitivities of the electrochemical measurements to ErbB2 are found to be 20.47 μA μM −1 cm −2 in a range from 1 fM to 0.1 μM, and those of the SPR measurements to be 1.35 nm μM −1 in a range from 10 pM to 1 nM, and 0.80 nm μM −1 in a range from 1 nM to 0.1 μM. The integrated dual-modality sensor offers higher sensitivity (through higher surface area and diffusions from nanoposts for electrochemical measurements), as well as the dynamic measurements of antigen–antibody bindings (through the SPR measurement), while operating simultaneously in a same sensing area using the same sample volume.