ABSTRACT
Drying of biologically-relevant sessile droplets, including passive systems such as DNA, proteins, plasma, and blood, as well as active microbial systems comprising bacterial and algal dispersions, has garnered considerable attention over the last decades. Distinct morphological patterns emerge when bio-colloids undergo evaporative drying, with significant potential in a wide range of biomedical applications, spanning bio-sensing, medical diagnostics, drug delivery, and antimicrobial resistance. Consequently, the prospects of novel and thrifty bio-medical toolkits based on drying bio-colloids have driven tremendous progress in the science of morphological patterns and advanced quantitative image-based analysis. This review presents a comprehensive overview of bio-colloidal droplets drying on solid substrates, focusing on the experimental progress during the last ten years. We provide a summary of the physical and material properties of relevant bio-colloids and link their native composition (constituent particles, solvent, and concentrations) to the patterns emerging due to drying. We specifically examined the drying patterns generated by passive bio-colloids (e.g., DNA, globular, fibrous, composite proteins, plasma, serum, blood, urine, tears, and saliva). This article highlights how the emerging morphological patterns are influenced by the nature of the biological entities and the solvent, micro- and global environmental conditions (temperature and relative humidity), and substrate attributes like wettability. Crucially, correlations between emergent patterns and the initial droplet compositions enable the detection of potential clinical abnormalities when compared with the patterns of drying droplets of healthy control samples, offering a blueprint for the diagnosis of the type and stage of a specific disease (or disorder). Recent experimental investigations of pattern formation in the bio-mimetic and salivary drying droplets in the context of COVID-19 are also presented. We further summarized the role of biologically active agents in the drying process, including bacteria, algae, spermatozoa, and nematodes, and discussed the coupling between self-propulsion and hydrodynamics during the drying process. We wrap up the review by highlighting the role of cross-scale in situ experimental techniques for quantifying sub-micron to micro-scale features and the critical role of cross-disciplinary approaches (e.g., experimental and image processing techniques with machine learning algorithms) to quantify and predict the drying-induced features. We conclude the review with a perspective on the next generation of research and applications based on drying droplets, ultimately enabling innovative solutions and quantitative tools to investigate this exciting interface of physics, biology, data sciences, and machine learning.
Subject(s)
COVID-19 , Male , Humans , COVID-19/diagnosis , Colloids/chemistry , Drug Delivery Systems , Solvents , Blood ProteinsABSTRACT
Interferometric scattering microscopy is a newly emerging alternative to fluorescence microscopy in biomedical research and diagnostic testing due to its ability to detect nano-objects such as individual proteins, extracellular vesicles, and virions individually through their intrinsic elastic light scattering. To improve the signal-to-noise ratio, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a photonic crystal (PC) resonator is used as the sample substrate. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create intensity contrast. Importantly, the scattered photons assume the wavevectors defined by PC's photonic band structure, resulting in the ability to utilize a non-immersion objective without significant loss at illumination density as low as 25 W/cm2. We demonstrate virus and protein detection, including highly selective capture and counting of intact pseudotype SARS-CoV-2 from saliva with sensitivity equivalent to conventional nucleic acid tests. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies, and as a single step, room temperature, and rapid viral detection technology. © 2022 SPIE.
ABSTRACT
We present an open source, fully wireless potentiostat (the “NanoStat”) for applications in electrochemistry, sensing, biomedical diagnostics, and nanotechnology, based on only 2 integrated circuit chips: A digital microcontroller with integrated on board WiFi and file/web server hardware/software, and an analog front end. This versatile platform is fully capable of all modern electrochemisty assays, including cyclic voltammetry, square wave voltammetry, chronoamperometry, and normal pulse voltammetry. The user interface is a web browser connected over http. All the code (firmware, HTML5, JavaScript) is hosted by the NanoStat itself without the need for any additional software. The total size is 4×40×20 mm and battery operation for 6 h is demonstrated, possible to extend to weeks or months in sleep mode. We anticipate that the applications of this could be very broad, from biomedical sensing in the clinic, to remote monitoring of unattended “motes”, to even possibly sensing aerial pathogens such as COVID in large public spaces without the need for anything other than a web browser for remote monitoring from anywhere in the world. Finally, we propose to use this software suite as a basis (kernel) of a fully open source, general purpose, web based electrochemistry software suite, ed from the hardware, which we call “OpenEChem”. © 2022