This PDF file contains the front matter associated with SPIE Proceedings Volume 11979, including the Title Page, Copyright information, and Table of Contents.

Whispering Gallery Mode (WGM) microresonators are a powerful class of optical devices with the ability to confine light within a small volume. These devices offer the advantages of high sensitivity, diversities in their geometries to meet the needs of different applications, and ease of integration with conventional electronic systems. Among various kinds of WGM resonators, microbubble resonators are a unique type of WGM device in which the optical and fluidic components are combined. We have developed a packaged silica microbubble resonator device for biosensing applications. HF etching is used to control the wall thickness and approach to the quasi-droplet regime in the packaged devices.

We demonstrate an EP-based sensor based on exceptional point(EP) of nanocylinders-loaded silicon microring for single particle detection. The EP is implemented by tailoring the spatial phase difference between the two nanocylinders placed close to the microring. When a nanoparticle is adsorbed onto the surface of the silicon microring, the degeneracy of two eigenvectors of the silicon microring is lifted, leading to mode splitting in the transmission spectrum. The wavelength difference of the split-mode is proportional to the square-root of the perturbation. To the best of our knowledge, this is the first sensor leveraging the EP of a silicon microring for single nanoparticle detection

Aflatoxin M1 (AFM1) is a carcinogenic compound usually found in milk, especially in developing countries. Significantly, AFM1 remains stable in milk even during pasteurization and heat treatments and thus poses a health hazard to humans, particularly children. Currently, well-established methods for detecting AFM1 include ELISA and chromatography. Although these approaches are reasonably accurate, they require a skilled workforce, costly setups, and several hours to generate results. We demonstrate the first application of wavelength-scanned cavity attenuated phase shift spectroscopy (WS-CAPS) in fiber cavities for AFM1 sensing to overcome the problems mentioned above. We build the sensor by forming a cavity with two fiber Bragg gratings. An SMF28 tapered fiber is spliced into the cavity as a sensing head. We bioconjugate the tapered fiber with DNA aptamers and validate the functionalization with EDX analysis. We use the coupled-mode theory to arrive at mathematical equations for conducting the WS-CAPS measurements. The WS-CAPS measurements primarily include detecting the phase of an output sinusoid with respect to an input sinusoid coming from a wavelength and amplitude modulated laser. The phase changes are directly related to AFM1 binding events at the functionalized tapered fiber. Our demonstrated sensor can detect AFM1 as low as 20 ppt (20 ng/L) in an aqueous solution, which is better than the safety limits imposed by European and USA regulatory bodies. In contrast to traditional CAPS systems with free space cavities, our WS-CAPS sensing modality allows us to use a source wavelength independent of an analyte's absorption. We strongly believe that the current work will lead towards developing accurate, rapid, and specialist-free sensors for a wide variety of applications in food security and point-of-care settings, especially for low-resource settings.

The COVID-19 pandemic demands fast, sensitive, and specific diagnostic tools for virus surveillance and containment. Current methods for diagnosing the COVID-19 are based on direct detection of either viral antigens or viral ribonucleic acids (RNA) in swab samples. Antigen-targeting tests are simple, have fast turnaround times, and allow rapid testing. Unfortunately, compared with viral RNA-targeting tests, their sensitivity is low, especially during the initial stages of the disease, which limits their adoption and implementation. Direct detection of SARS-CoV-2 RNA using reversetranscription quantitative polymerase chain reaction (RT-qPCR) is sensitive and specific, making it a golden standard in SARS-CoV-2 detection. However, it had not seen a significant update since its introduction three decades ago. It has a long turnaround time, requires a high number of amplification cycles, and a complicated and expensive detection system for real-time monitoring of the signal. While insignificant for research applications, these limitations present severe problems for mass testing required to contain the disease. Here, we introduce a diagnostic platform for rapid and highly sensitive clinical diagnosis of COVID-19. Based on the biochemical principles of the RT-PCR, it utilizes the endpoint detection by the magnetic modulation biosensing (MMB) system, allowing the detection of as little as two copies of SARS-CoV-2 in ~30 minutes. Testing 309 RNA samples from verified SARS-CoV-2 carriers and healthy subjects resulted in 97.8% sensitivity, 100% specificity, and 0% crossreactivity. This level of performance is on par with the gold standard (RT-qPCR) but requires 1/3 of the time. The platform can be easily adapted to detect almost any other pathogen of choice.

The outbreak of the coronavirus disease emphasized the need for fast and sensitive inhibitor screening tools for the identification of new drug candidates. In SARS-CoV-2, one of the initial steps in the infection cycle is the adherence of the receptor-binding domain (RBD) of the spike protein 1 (S1) to the host cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, inhibition of S1-ACE2 interaction may block the entry of the virus to the host cell, and thus may limit the spread of the virus in the body. We demonstrate a rapid and quantitative method for the detection and classification of different types of molecules as inhibitors or non-inhibitors of the S1-ACE2 interaction using magnetically modulated biosensors (MMB). In the MMB-based assay, magnetic beads are attached to the S1 protein and the ACE2 receptor is fluorescently labeled. Thus, only when the proteins interact, the fluorescent molecule is connected to the magnetic bead. To increase the sensitivity of fluorescence detection, the complex of magnetic beads and attached fluorescent molecules are aggregated by two opposing electromagnets and are moved from side to side in a periodic motion in and out of a laser beam, emitting a flashing signal that is collected by a digital camera. When an inhibitor interferes with the interaction, the signal is reduced. The MMB-based assay is much faster and has minimal non-specific binding than the commonly used ELISA. It can be adjusted to other interactions, and therefore can be utilized as a global tool for inhibitor screening.

We investigate the utility of various statistical and machine learning techniques for classifying and quantifying selected proteins using an array of porous silicon sensors with uniquely tuned properties. No capture agents or bioreceptors are utilized for the protein detection. The sensing approach relies on differences in non-specific physisorption and represents a step towards a new low cost, simple and robust sensor platform that can detect a vast range of biomolecules.

Ultrabithorax (Ubx) is a Hox gene transcription factor regulating the growth of wings and limbs in Drosophila melanogaster. However, the protein can also be produced recombinantly, and can self-assemble to form a film at the air-water interface. Materials drawn from this film, including fibres and thin coatings, are elastic, bio- and cyto-compatible. Moreover, Ubx can be functionalised with other biomolecules to form protein fusions. In this work, the physical properties of Ubx fibres and electrospun mats containing Ubx were investigated. An electrical conductivity comparable to semiconductors was discovered in enhanced green fluorescent protein- Ubx (EGFP-Ubx) fibres. The photoluminescence properties of pure Ubx, EGFP-Ubx, and electrospun poly(ethylene oxide)/EGFP-Ubx complexes were compared and the fluorescence emission peaks were found at 420nm for poly(ethylene oxide), 442nm for Ubx, and 512nm for EGFP. Moreover, the effect of material production method on the fluorescence lifetime was investigated and revealed differences between self-assembled microfibres and electrospun mats with fibre diameters below 1 μm. Finally, Ubx fibres were functionalised with DNA aptamers, and E.coli binding was increased using three different aptamers compared to pure fibres. The increase was 15% increase for the P12 aptamer, 92% for the STC12 aptamer, and 167% for the Antibac2 aptamer. Developments in large-scale material formation could support the functional Ubx materials in becoming a platform material for biosensing and tissue regeneration.

In the last decade, among the various cerebral ischemia biomarkers, microRNAs (miRNAs, MW 7-10 kDa) have recently attracted the attention of researchers. These are short endogenous biomolecules of noncoding ribonucleic acids that negatively regulate gene expression. The presence of miRNAs in blood and the ability to measure their level in a non-invasive way, the so-called liquid biopsy approach, has opened new doors in the search for peripheral biomarkers for the diagnosis and prognosis of diseases such as hemorrhagic stroke. In order to perform liquid biopsy, Bloch surface waves supported by one dimensional photonic crystals are exploited to enhance and redirect the fluorescence arising from a sandwiched miRNA recognition assay. Besides, the sensing elements consist of disposable and low-cost plastic biochips coated with a 1DPC. The assay format consists of a first partial hybridization of an oligonucleotidic probe, immobilized onto the 1DPC surface in five regions, with the miRNA target (miR-16-5p, hemorrhagic stroke biomarker) to be revealed in a complex biological medium. The protocol is then completed with a second partial hybridization of the miRNA target with a second synthetic oligonucleotide conjugated with an organic dye. This last step permits to specifically introduce fluorescence where the sandwich assay is accomplished. Thanks to the present technique, we are able to detect miRNA target solutions with a limit of detection of 32 ng/mL in less than 60 minutes. In conclusion, since the recommended therapeutic window is very limited, biomarkers for cerebral ischemia/hemorrhage have the potential to speed-up diagnosis and the assignment of treatments.

Bonellia viridis, a green marine echiuran worm known since the early 19th century in the Mediterranean Sea, typically lives in sediments or rock crevices at a depth underwater of 3–10 m, causing acquisition of samples to generally require diving. The size of the main body trunk of the female is about 8 cm, whereas the (dwarf) male is 1 to 3 mm long and lives inside the female. The green pigmentation of B. viridis stems from bonellin, a tetrapyrrole macrocycle containing a chlorin chromophore. Bonellin is believed to exert diverse physiological functions (masculinization and sex determination, chemical defense, cytotoxicity, and antimicrobial activity) but not photosynthesis as for the better known native chlorin, chlorophyll. The existence of bonellin poses physiological, biosynthetic, and evolutionary questions. Here, we report in-depth assessment of information concerning tides at a wide shallow beach in Okinawa, identifying narrowly restricted periods when acquisition of Bonellia specimens could be pursued without diving. Indeed, <15 specimens of B. sp. were collected from Odo beach, Itoman city, Okinawa prefecture, Japan [26°09' N, 127°71' E], at midnight on days when the tides were exceptionally low: March 6–12, 2016; December 22–27, 2018; and January 18–25, 2019. The specimens were acquired manually from small tidal pools upon walking near the outer reef flat (~300 m from the shore) during the extremely low tides. Reasonably facile access without diving to Bonellia in a region distant from the Mediterranean should expand study of the diversity of these unusual green worms.