arXiv subjects

Fareeha Safir

Publications and source records attributed to Fareeha Safir.

4 recordsLinked to original sources

arXiv2024

High-throughput antibody screening with high-quality factor nanophotonics and bioprinting

Empirical investigation of the quintillion-scale, functionally diverse antibody repertoires that can be generated synthetically or naturally is critical for identifying potential biotherapeutic leads, yet remains burdensome. We present high-throughput nanophotonics- and bioprinter-enabled screening (HT-NaBS), a multiplexed assay for large-scale, sample-efficient, and rapid characterization of antibody libraries. Our platform is built upon independently addressable pixelated nanoantennas exhibiting wavelength-scale mode volumes, high-quality factors (high-Q) exceeding 5000, and pattern densities exceeding one million sensors per square centimeter. Our custom-built acoustic bioprinter enables individual sensor functionalization via the deposition of picoliter droplets from a library of capture antigens at rates up to 25,000 droplets per second. We detect subtle differentiation in the target binding signature through spatially-resolved spectral imaging of hundreds of resonators simultaneously, elucidating antigen-antibody binding kinetic rates, affinity constant, and specificity. We demonstrate HT-NaBS on a panel of antibodies targeting SARS-CoV-2, Influenza A, and Influenza B antigens, with a sub-picomolar limit of detection within 30 minutes. Furthermore, through epitope binning analysis, we demonstrate the competence and diversity of a library of native antibodies targeting functional epitopes on a priority pathogen (H5N1 bird flu) and on glycosylated therapeutic Cetuximab antibodies against epidermal growth factor receptor. With a roadmap to image tens of thousands of sensors simultaneously, this high-throughput, resource-efficient, and label-free platform can rapidly screen for high-affinity and broad epitope coverage, accelerating biotherapeutic discovery and de novo protein design.

physics.optics↗

arXiv2024

Very-Large-Scale-Integrated High-$Q$ Nanoantenna Pixels (VINPix)

Metasurfaces provide a versatile and compact approach to free-space optical manipulation and wavefront shaping. Comprised of arrays of judiciously-arranged dipolar resonators, metasurfaces precisely control the amplitude, polarization, and phase of light, with applications spanning imaging, sensing, modulation, and computing. Three crucial performance metrics of metasurfaces and their constituent resonators are the quality factor ($Q$-factor), mode-volume ($V_m$), and the ability to control far-field radiation. Often, resonators face a trade-off between these parameters: a reduction in $V_m$ leads to an equivalent reduction in $Q$, albeit with more control over radiation. Here, we demonstrate that this perceived compromise is not inevitable $-$ high-$Q$, subwavelength $V_m$, and controlled dipole-like radiation can be achieved, simultaneously. We design high-$Q$, very-large-scale integrated silicon nanoantenna pixels $-$ VINPix $-$ that combine guided mode resonance waveguides with photonic crystal cavities. With optimized nanoantennas, we achieve $Q$-factors exceeding 1500 with $V_m$ less than 0.1 $(λ/n_{\text{air}})^3$. Each nanoantenna is individually addressable by free-space light, and exhibits dipole-like scattering to the far-field. Resonator densities exceeding a million nanoantennas per $\text{cm}^2$ can be achieved, as demonstrated by our fabrication of an 8 mm x 8 mm VINPix array. As a proof-of-concept application, we demonstrate spectrometer-free, spatially localized, refractive-index sensing utilizing a VINPix array. Our platform provides a foundation for compact, densely multiplexed devices such as spatial light modulators, computational spectrometers, and in-situ environmental sensors.

physics.optics↗

arXiv2023

Combining acoustic bioprinting with AI-assisted Raman spectroscopy for high-throughput identification of bacteria in blood

Identifying pathogens in complex samples such as blood, urine, and wastewater is critical to detect infection and inform optimal treatment. Surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) can distinguish among multiple pathogen species, but processing complex fluid samples to sensitively and specifically detect pathogens remains an outstanding challenge. Here, we develop an acoustic bioprinter to digitize samples into millions of droplets, each containing just a few cells, which are identified with SERS and ML. We demonstrate rapid printing of 2 pL droplets from solutions containing S. epidermidis, E. coli, and blood; when mixed with gold nanorods (GNRs), SERS enhancements of up to 1500x are achieved.We then train a ML model and achieve >=99% classification accuracy from cellularly-pure samples, and >=87% accuracy from cellularly-mixed samples. We also obtain >=90% accuracy from droplets with pathogen:blood cell ratios <1. Our combined bioprinting and SERS platform could accelerate rapid, sensitive pathogen detection in clinical, environmental, and industrial settings.

physics.bio-ph↗

arXiv2022

Rapid genetic screening with high quality factor metasurfaces

Genetic analysis methods are foundational to advancing personalized and preventative medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and DNA microarrays rely on fluorescence and absorbance, necessitating sample amplification or replication and leading to increased processing time and cost. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with monolayers of nucleic acid fragments. Each nanoantenna exhibits substantial electromagnetic field enhancements with sufficiently localized fields to ensure isolation from neighboring resonators, enabling dense biosensor integration. We quantitatively detect complementary target sequences using DNA hybridization simultaneously for arrays of sensing elements patterned at densities of 160,000 pixels per cm$^2$. In physiological buffer, our nanoantennas exhibit average resonant quality factors of 2,200, allowing detection of two gene fragments, SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b), down to femtomolar concentrations. We also demonstrate high specificity sensing in clinical nasopharyngeal eluates within 5 minutes of sample introduction. Combined with advances in biomarker isolation from complex samples (e.g., mucus, blood, wastewater), our work provides a foundation for rapid, compact, amplification-free and high throughput multiplexed genetic screening assays spanning medical diagnostics to environmental monitoring.

physics.optics↗