The hour-glass type nanostructures are fabricated by using the conventional Si processes. When beaming though these structures, we observed that light is collected by the micro scale pyramidal cavity, funneled through the nano-aperture by plasmonic resonance and collimated with enhanced transmission by the surrounding horn-like mirrors (optical horn-effect). Our research confirmed the strong plasmonic coupling. Optical transmissions through pyramidal probes with various nano-aperture diameters were measured to be dependent upon the aperture area. For a diameter less than ~ 50 nm or less than area with ~10,000 nm2, the transmitted optical intensities are increasing due to the spp-mediated intra-band emission. For the (7x7) slit aperture array platform with a ~ 10 nm aperture width, the broad emission spectra ranging from 600 nm to 860 nm are observed possibly due to nearfield coupling with LSPP.

Dielectric metasurfaces support resonances that are widely explored for biosensing and imaging. High Q-factors are desirable for refractive index sensing while strong localisation is desirable for imaging resolution. Metasurfaces typically provide a trade-off between Q-factor and light localisation. We have demonstrated a dielectric nanohole array metasurface that concurrently optimize the structure for both imaging and biochemical sensing. For sensing we have verified LOD=1pg/mL for IgG, confirming the suitability for detecting clinically relevant concentrations. For imaging, the submicrometer spatial resolution of the metasurface allows to resolve individual Escherichia coli bacteria, which can pave the way for new studies in antimicrobial resistance.

The programmable nature of sequence-specific targeting by CRISPR-Cas nucleases has revolutionized a wide range of genomic applications and is now emerging as a new method for nucleic acid detection. This talk explores the diversity of CRISPR systems and how their fundamental mechanisms have enabled novel methods for target recognition and readout, highlighting the intersection of biology and engineering. We further discuss the advances and potential for CRISPR-based detection to have an impact across a continuum of diagnostic applications, particularly as it relates to the COVID-19 pandemic.

Here, we introduce a diagnostic platform for the detection of SARS-CoV-2. It utilizes the biochemical principles of the RT-qPCR, combined with the end-point detection by the magnetic modulation biosensing (MMB) system. The platform allows detection of ten copies of the SARS-CoV-2 target in 30 minutes. Testing of 200 RNA samples of clinical patients and healthy subjects resulted in 98% sensitivity and 100% selectivity. This is as good or better than the gold standard (RT-qPCR), requiring 1/3 of the time, with cheaper equipment and off-the-shelf reagents. The platform can be easily adapted to detect almost any other pathogen of choice.

The ongoing COVID-19 pandemic highlights the need for simple and rapid testing for respiratory infections at the point-of-care. With its high sensitivity and specificity, RT-PCR is the gold standard for the molecular diagnosis and differentiation among respiratory pathogens, but it requires complex instrumentation and methods that are not suitable for point-of-care settings. Our simplified Adaptive PCR technology and workflow yields high analytic performance without the complexities of traditional PCR by incorporating mirror-image L-DNA enantiomers—identical in sequence to PCR primers and targets—that are optically monitored to adapt cycling conditions to match the biochemical contents of the sample in real time. This enables rapid, single-tube analyses directly from COVID-19 swab specimens without RNA extraction.

Rapid detection of viral agents with high sensitivity, high specificity, and minimal cross-reactivity is a leading, unmet challenge in diagnostics. Using Magnetic Modulation Biosensing (MMB) platform and a thorough analysis of large libraries of antibodies and patients’ clinical samples, we developed quantitative serological assays to detect antiviral immune response components for dengue, Zika, and severe acute respiratory syndrome coronavirus 2 (SARS2). We demonstrate much higher clinical sensitivity and specificity compared with the state-of-the-art ELISA assays. Allowing significant improvement in public health measures, prevent the spread of diseases, and enables simple operation in low-resource settings.

Bio-integrated lasers, that are lasers implanted into cells and tissues, are gaining interest from the research community. Here we show how mirolasers based on whispering gallery modes can be used for sensing different processes in biological materials including inside cells. By making lasers of a predefined size they can also be used to encode some information and for cell tracking. Sensing and tracking can be applied to highly scattering tissues.

The first demonstration of molecular barcoding analysis based on wavelength-tunable lasers was demonstrated, where distinctive laser emission wavelengths are utilized to quantify molecular interactions. Taking advantage of the light-harvesting effect, the concept of interfacial energy transfer was exploited on whispering-gallery-mode (WGM) droplet laser by separating donor and acceptor molecules at the cavity interface. The concept of “molecular laser barcode” was demonstrated with versatile biosensing functions through FRET and ELISA. Our work shows great impact in both biomedical sensing and fundamental research in biology, paving a new road for biomedical analysis.

We demonstrated a fully functional, controllable, and biocompatible microlaser by using hydrogels. Lasing was observed from FITC and RhB encapsulated in inkjet-printed hydrogel cavity. Furthermore, FITC-RhB FRET pairs were applied to demonstrate the potential use of such hydrogel array on analysis of biomedical interaction. The realization of hydrogel laser marks a critical step for employing hydrogel laser in a wide range of biomedical applications. As such, various biomolecules and fluorophores could be encapsulated within the hydrogel to form lasing at desirable wavelengths, paving a new way for high throughput biomedical analysis.

In this talk, we present efforts to study protein phosphorylation, a biochemical reaction responsible for a broad range of signal transduction roles. We designed microfluidic reactors based on tubular flow for studying reactor kinetic parameters in protein phosphorylation. We probed the environment where the reaction takes place without influencing the reactor kinetics, while collecting molecular information such as structure and conformation of native proteins. We designed and tested PDMS microfluidic reactors and found significant absorption of important Raman bands from the PDMS. Our redesigned microfluidic reactors demonstrated the measurement of phosphate bonds involved in the protein phosphorylation reaction.

The rapidly advancing field of photonic biosensors has led to the demonstration of devices that allow for label-free, quantitation of biomolecules in a low-power, small-footprint format. We hypothesized that combining photonic sensor technology with inexpensive and widely available, paper-based Lateral Flow Assay (LFA) formats would yield a device suitable for the Point-of-Care diagnostic space. Resonance-based sensor chips were post-processed to allow bulk material to interact with single-mode TE light. These sensors achieved a bulk refractive index sensitivity of 170 nm/RIU. We then paired a sensor with paper-based microfluidic LFAs to place labeled antibodies within the evanescent field of the Si3N4 waveguides. Finally, we developed nitrocellulose-based lateral flow immunoassays to determine the ability of the system to detect specific protein binding events. This discussion will focus on device processing and assay development for biomolecule detection at the Point-of-Care.

Inhibitor screening is an important tool for drug development, especially during the latest COVID-19 pandemic. The commonly used ELISA-based tool is time consuming, tedious, and lacks sensitivity. Here, we demonstrate the utility of a magnetic modulation biosensing (MMB) system for rapid and highly sensitive screening of inhibitors for the S1-ACE2 interaction of SARS-CoV-2. We detected the interaction in a few hours with minimal non-specific binding. Different inhibitors were identified, such as neutralizing antibodies and peptides, and their potency was quantitatively assessed. We anticipate that our method will lead to a remarkable advance in screening for new drug candidates.

A methodology for chemical sensing of the quantity of a target material in a given sample which employs biosensing bioluminescent bacteria is presented. Variations in the signal between different bacteria batches and changing environmental condition are overcome by in-situ comparison between responses produced by the inspected sample, and a standard sample containing a known quantity of the target material. Measurements of DNT concentrations up to 50 ppm were demonstrated. Extension of the concentration range is obtained by parallel measurements of the responses produced by different types of bacteria, each optimized to a different segment of the concentration range.

Detection of biomarkers at low concentrations is essential for early diagnosis of numerous diseases. In many sensitive assays, the target molecules are tagged using fluorescently labeled probes and captured using magnetic beads. Current devices rely on quantifying the target molecules by detecting the fluorescent signal from individual beads. Here, we propose a high throughput optical modulated biosensing (OMB) system. Using the device to detect human Interleukin-8, we demonstrated a 0.03 ng/L limit of detection and a 4-log dynamic range, performance which is on par with the most sensitive devices, but is achieved without their bulk and cost.

We present a signal processing method capable of significantly lowering the detection limit of thin film optical biosensors. The signal processing method drastically reduces noise contributions typically encountered in sensor measurements. Application of the signal processing method is demonstrated on single-layer porous silicon optical biosensors operating in both buffered solutions and complex media.

When dealing with sensing of (bio)molecules the length scale of targets may vary over more than 2 orders of magnitude moving from elementary ions and molecules (0.1 to 1 nm) to complex proteins and virus (1 to 100 nm). A number of technologies have been proposed to prepare fluidic structures and systems with length scales enabling an effective interaction with the specific molecular target. Among these, electrochemical micro and nano structuring of silicon is increasingly attracting attention at research level for biosensing and microfluidics. In this talk, state-of-the-art research on silicon nano-micro structures and systems prepared by electrochemical etching for high-sensitivity (bio)sensing, among which, interferometers for ultra-high-sensitivity ion measurements in water, optical platforms for point-of-care clinical diagnostics, drop-and-measure photonic crystal systems for in-field optical biosensing, microneedles for transdermal biosensing, is presented and discussed.

Wash-swabs of common locations in public places were analyzed by surface-enhanced Raman spectroscopy (SERS) during COVID-19 pandemic to find results’ correlation with statistics on infected people number. SERS-spectra anomalies were not chaotic and could potentially help to predict pandemic stages. We used radically new SERS-nanovoids in which drops of analyte were softly affected with uniform volumetric “cloud” of electromagnetic field. SERS-nanovoids were formed in Bisphenol A Novolac epoxy resin (SU-8) using soft lithography followed by sputtering of gold. Nanovoids provided recording reproducible SERS-signatures containing characteristic bands of wash-swabs’ components and showed much better reproducibility of SERS-spectra than traditional SERS-nanoparticles.