Virus detection using nanoparticles and deep neural network–enabled smartphone system

Chen H., Li Z., Zhang L., Sawaya P., Shi J., Wang P.

Quantitating ultra-low concentrations of protein biomarkers is critical for early disease diagnosis and treatment. However, most current point-of-care (POC) assays are limited in sensitivity. Herein, we introduce an ultra-sensitive and facile microbubbling assay for the quantification of protein biomarkers with a digital-readout method that requires only a smartphone camera. We used machine learning to develop a smartphone application for automated image analysis to facilitate accurate and robust counting. Using this method, post-prostatectomy surveillance of prostate specific antigen (PSA) can be achieved with a detection limit (LOD) of 2.1 fm (0.060 pg mL-1 ), and early pregnancy detection using βhCG can be achieved with a of 0.034 mIU mL-1 (2.84 pg mL-1 ). This work provides the proof-of-principle of the microbubbling assay with a digital readout as an ultra-sensitive technology with minimal requirement for power and accessories, facilitating future POC applications.

Liu L., Liu J., Huang H., Li Y., Zhao G., Dou W.

Inspired by the very popular demonstration, Elephant's Toothpaste, we developed a cost-effective, portable foam immunoassay for quantitative detection of Escherichia coli O157:H7 (E. coli O157:H7) by measuring foam volume changes using a low-cost ruler. This quantitative immunoassay for E. coli O157:H7 is built by integrating a catalyzed foam-generation reaction with pathogen recognition component. E. coli O157:H7 was enriched and captured by monoclonal antibody to E. coli O157:H7 (mAb1) modified Fe3O4 magnetic nanoparticles (MNP). The peroxidase-like nanozymes gold and platinum nanoparticles (Au@Pt NP) were loaded on silica nanoparticle (SiO2 NP), forming Au@Pt/SiO2 NP. The Au@Pt/SiO2 NP were functionalized by antibody against E. coli O157:H7 (mAb2-Au@Pt/SiO2 NP) and used as signal labels. In the final sandwich immune complex, Au@Pt NP catalyzes the hydrolysis of hydrogen peroxide (H2O2) to produce oxygen (O2). In the presence of sodium dodecyl sulfate (SDS), O2 is trapped by SDS forming thick foam. The foam rises in an acrylic tube and produces sensitive height readout. There is a linear relationship between the foam height and the logarithm of E. coli O157:H7 concentration. Under the optimum conditions, the detection limit was 2.16 × 102 CFU·mL−1 (3σ) in the range of 1.19 × 103–1.19 × 107 CFU·mL−1. This method demonstrates good practical application potential during detection of E. coli O157:H7 in milk samples. This new signaling strategy opens up a new way for portable, simple and sensitive on-site analysis in various environments.

Wood C.S., Thomas M.R., Budd J., Mashamba-Thompson T.P., Herbst K., Pillay D., Peeling R.W., Johnson A.M., McKendry R.A., Stevens M.M.

Mobile health, or ‘mHealth’, is the application of mobile devices, their components and related technologies to healthcare. It is already improving patients’ access to treatment and advice. Now, in combination with internet-connected diagnostic devices, it offers novel ways to diagnose, track and control infectious diseases and to improve the efficiency of the health system. Here we examine the promise of these technologies and discuss the challenges in realizing their potential to increase patients’ access to testing, aid in their treatment and improve the capability of public health authorities to monitor outbreaks, implement response strategies and assess the impact of interventions across the world. Combining mobile phone technologies with infectious disease diagnostics can increase patients’ access to testing and treatment and provide public health authorities with new ways to monitor and control outbreaks of infectious diseases.

Draz M.S., Kochehbyoki K.M., Vasan A., Battalapalli D., Sreeram A., Kanakasabapathy M.K., Kallakuri S., Tsibris A., Kuritzkes D.R., Shafiee H.

HIV-1 infection is a major health threat in both developed and developing countries. The integration of mobile health approaches and bioengineered catalytic motors can allow the development of sensitive and portable technologies for HIV-1 management. Here, we report a platform that integrates cellphone-based optical sensing, loop-mediated isothermal DNA amplification and micromotor motion for molecular detection of HIV-1. The presence of HIV-1 RNA in a sample results in the formation of large-sized amplicons that reduce the motion of motors. The change in the motors motion can be accurately measured using a cellphone system as the biomarker for target nucleic acid detection. The presented platform allows the qualitative detection of HIV-1 (n = 54) with 99.1% specificity and 94.6% sensitivity at a clinically relevant threshold value of 1000 virus particles/ml. The cellphone system has the potential to enable the development of rapid and low-cost diagnostics for viruses and other infectious diseases. Micromotors have a range of potential healthcare applications. Here, the authors describe the development of a metal nanoparticle DNA micromotor which can be used to detect human HIV-1 by a change in the motion of the micromotors, monitored by cell phone camera, triggered by binding of HIV-1 RNA.

Draz M.S., Lakshminaraasimulu N.K., Krishnakumar S., Battalapalli D., Vasan A., Kanakasabapathy M.K., Sreeram A., Kallakuri S., Thirumalaraju P., Li Y., Hua S., Yu X.G., Kuritzkes D.R., Shafiee H.

Zika virus (ZIKV) infection is an emerging pandemic threat to humans that can be fatal in newborns. Advances in digital health systems and nanoparticles can facilitate the development of sensitive and portable detection technologies for timely management of emerging viral infections. Here we report a nanomotor-based bead-motion cellphone (NBC) system for the immunological detection of ZIKV. The presence of virus in a testing sample results in the accumulation of platinum (Pt)-nanomotors on the surface of beads, causing their motion in H2O2 solution. Then the virus concentration is detected in correlation with the change in beads motion. The developed NBC system was capable of detecting ZIKV in samples with virus concentrations as low as 1 particle/μL. The NBC system allowed a highly specific detection of ZIKV in the presence of the closely related dengue virus and other neurotropic viruses, such as herpes simplex virus type 1 and human cytomegalovirus. The NBC platform technology has the potential to be used in the development of point-of-care diagnostics for pathogen detection and disease management in developed and developing countries.

Duan X., Li S., Holmes J.A., Tu Z., Li Y., Cai D., Liu X., Li W., Yang C., Jiao B., Schaefer E.A., Fusco D.N., Salloum S., Chen L., Lin W., et. al.

ABSTRACT Hepatitis C virus (HCV) infection has been shown to regulate microRNA 130a (miR-130a) in patient biopsy specimens and in cultured cells. We sought to identify miR-130a target genes and to explore the mechanisms by which miR-130a regulates HCV and hepatitis B virus (HBV) replication. We used bioinformatics software, including miRanda, TargetScan, PITA, and RNAhybrid, to predict potential miR-130a target genes. miR-130a and its target genes were overexpressed or were knocked down by use of small interfering RNA (siRNA) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 guide RNA (gRNA). Selected gene mRNAs and their proteins, together with HCV replication in OR6 cells, HCV JFH1-infected Huh7.5.1 cells, and HCV JFH1-infected primary human hepatocytes (PHHs) and HBV replication in HepAD38 cells, HBV-infected NTCP-Huh7.5.1 cells, and HBV-infected PHHs, were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting, respectively. We selected 116 predicted target genes whose expression was related to viral pathogenesis or immunity for qPCR validation. Of these, the gene encoding pyruvate kinase in liver and red blood cell (PKLR) was confirmed to be regulated by miR-130a overexpression. miR-130a overexpression (via a mimic) knocked down PKLR mRNA and protein levels. A miR-130a inhibitor and gRNA increased PKLR expression, HCV replication, and HBV replication, while miR-130a gRNA and PKLR overexpression increased HCV and HBV replication. Supplemental pyruvate increased HCV and HBV replication and rescued the inhibition of HCV and HBV replication by the miR-130a mimic and PKLR knockdown. We concluded that miR-130a regulates HCV and HBV replication through its targeting of PKLR and subsequent pyruvate production. Our data provide novel insights into key metabolic enzymatic pathway steps regulated by miR-130a, including the steps involving PKLR and pyruvate, which are subverted by HCV and HBV replication. IMPORTANCE We identified that miR-130a regulates the target gene PKLR and its subsequent effect on pyruvate production. Pyruvate is a key intermediate in several metabolic pathways, and we identified that pyruvate plays a key role in regulation of HCV and HBV replication. This previously unrecognized, miRNA-regulated antiviral mechanism has implications for the development of host-directed strategies to interrupt the viral life cycle and prevent establishment of persistent infection for HCV, HBV, and potentially other viral infections.

Lange B., Roberts T., Cohn J., Greenman J., Camp J., Ishizaki A., Messac L., Tuaillon E., van de Perre P., Pichler C., Denkinger C.M., Easterbrook P.

The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Ivanova Reipold E., Easterbrook P., Trianni A., Panneer N., Krakower D., Ongarello S., Roberts T., Miller V., Denkinger C.

The current low access to virological testing to confirm chronic viraemic HCV infection in low- and middle-income countries (LMIC) is limiting the rollout of hepatitis C (HCV) care. Existing tests are complex, costly and require sophisticated laboratory infrastructure. Diagnostic manufacturers need guidance on the optimal characteristics a virological test needs to have to ensure the greatest impact on HCV diagnosis and treatment in LMIC. Our objective was to develop a target product profile (TPP) for diagnosis of HCV viraemia using a global stakeholder consensus-based approach. Based on the standardised process established to develop consensus-based TPPs, we followed five key steps. (i) Identifying key potential global stakeholders for consultation and input into the TPP development process. (ii) Informal priority-setting exercise with key experts to identify the needs that should be the highest priority for the TPP development; (iii) Defining the key TPP domains (scope, performance and operational characteristics and price). (iv) Delphi-like process with larger group of key stakeholder to facilitate feedback on the key TPP criteria and consensus building based on pre-defined consensus criteria. (v) A final consensus-gathering meeting for discussions around disputed criteria. A complementary values and preferences survey helped to assess trade-offs between different key characteristics. The following key attributes for the TPP for a test to confirm HCV viraemic infection were identified: The scope defined is for both HCV detection as well as confirmation of cure. The timeline of development for tests envisioned in the TPP is 5 years. The test should be developed for use by health-care workers or laboratory technicians with limited training in countries with a medium to high prevalence of HCV (1.5–3.5% and >3.5%) and in high-risk populations in low prevalence settings (<1.5%). A clinical sensitivity at a minimum of 90% is considered sufficient (analytical sensitivity of the equivalent of 3000 IU/ml), particularly if the test increases access to testing through an affordable price, increase ease-of-use and feasibility on capillary blood. Polyvalency would be optimal (i.e. ability to test for HIV and others). The only characteristic that full agreement could not be achieved on was the price for a virological test. Discussants felt that to reach the optimal target price substantial trade-offs had to be made (e.g. in regards to sensitivity and integration). The TPP and V&P survey results define the need for an easy-to-use, low cost test to increase access to diagnosis and linkage to care in LMIC.

Halliday J.E., Hampson K., Hanley N., Lembo T., Sharp J.P., Haydon D.T., Cleaveland S.

Emerging infectious diseases (EIDs) threaten the health of people, animals, and crops globally, but our ability to predict their occurrence is limited. Current public health capacity and ability to detect and respond to EIDs is typically weakest in low- and middle-income countries (LMICs). Many known drivers of EID emergence also converge in LMICs. Strengthening capacity for surveillance of diseases of relevance to local populations can provide a mechanism for building the cross-cutting and flexible capacities needed to tackle both the burden of existing diseases and EID threats. A focus on locally relevant diseases in LMICs and the economic, social, and cultural contexts of surveillance can help address existing inequalities in health systems, improve the capacity to detect and contain EIDs, and contribute to broader global goals for development.

Daaboul G.G., Freedman D.S., Scherr S.M., Carter E., Rosca A., Bernstein D., Mire C.E., Agans K.N., Hoenen T., Geisbert T.W., Ünlü M.S., Connor J.H.

Light microscopy is a powerful tool in the detection and analysis of parasites, fungi, and prokaryotes, but has been challenging to use for the detection of individual virus particles. Unlabeled virus particles are too small to be visualized using standard visible light microscopy. Characterization of virus particles is typically performed using higher resolution approaches such as electron microscopy or atomic force microscopy. These approaches require purification of virions away from their normal millieu, requiring significant levels of expertise, and can only enumerate small numbers of particles per field of view. Here, we utilize a visible light imaging approach called Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows automated counting and sizing of thousands of individual virions. Virions are captured directly from complex solutions onto a silicon chip and then detected using a reflectance interference imaging modality. We show that the use of different imaging wavelengths allows the visualization of a multitude of virus particles. Using Violet/UV illumination, the SP-IRIS technique is able to detect individual flavivirus particles (~40 nm), while green light illumination is capable of identifying and discriminating between vesicular stomatitis virus and vaccinia virus (~360 nm). Strikingly, the technology allows the clear identification of filamentous infectious ebolavirus particles and virus-like particles. The ability to differentiate and quantify unlabeled virus particles extends the usefulness of traditional light microscopy and can be embodied in a straightforward benchtop approach allowing widespread applications ranging from rapid detection in biological fluids to analysis of virus-like particles for vaccine development and production.

Perkel J.M.

Mobile phones are helping to take conventional laboratory-based science into the field, the classroom and the clinic.

Kanakasabapathy M.K., Sadasivam M., Singh A., Preston C., Thirumalaraju P., Venkataraman M., Bormann C.L., Draz M.S., Petrozza J.C., Shafiee H.

This work demonstrates that a low-cost smartphone accessory can be used for home-based male infertility screening.

Kong J.E., Wei Q., Tseng D., Zhang J., Pan E., Lewinski M., Garner O.B., Ozcan A., Di Carlo D.

Key challenges with point-of-care (POC) nucleic acid tests include achieving a low-cost, portable form factor, and stable readout, while also retaining the same robust standards of benchtop lab-based tests. We addressed two crucial aspects of this problem, identifying a chemical additive, hydroxynaphthol blue, that both stabilizes and significantly enhances intercalator-based fluorescence readout of nucleic acid concentration, and developing a cost-effective fiber-optic bundle-based fluorescence microplate reader integrated onto a mobile phone. Using loop-mediated isothermal amplification on lambda DNA we achieve a 69-fold increase in signal above background, 20-fold higher than the gold standard, yielding an overall limit of detection of 25 copies/μL within an hour using our mobile-phone-based platform. Critical for a point-of-care system, we achieve a >60% increase in fluorescence stability as a function of temperature and time, obviating the need for manual baseline correction or secondary calibration dyes. This field-portable and cost-effective mobile-phone-based nucleic acid amplification and readout platform is broadly applicable to other real-time nucleic acid amplification tests by similarly modulating intercalating dye performance and is compatible with any fluorescence-based assay that can be run in a 96-well microplate format, making it especially valuable for POC and resource-limited settings.

Lawrence P.B., Price J.L.

PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein therapeutics. The development of chemoselective side-chain modification reactions has enabled researchers to PEGylate proteins with high selectivity at defined locations. However, aside from avoiding active sites and binding interfaces, there are few guidelines for the selection of optimal PEGylation sites. Because conformational stability is intimately related to the ability of a protein to avoid proteolysis, aggregation, and immune responses, it is possible that PEGylating a protein at sites where PEG enhances conformational stability will result in PEG-protein conjugates with enhanced pharmacokinetic properties. However, the impact of PEGylation on protein conformational stability is incompletely understood. This review describes recent advances toward understanding the impact of PEGylation on protein conformational stability, along with the development of structure-based guidelines for selecting stabilizing PEGylation sites.

McCracken K.E., Yoon J.

Developments in the emerging fields of smartphone chemical and biosensing have dovetailed with increased interest in environmental and health monitoring for resource-limited environments, culminating in research toward field-ready smartphone sensors. Optical sensors have been a particular focus, in which smartphone imaging and on-board analysis have been integrated into both existing and novel colorimetric, fluorescent, chemiluminescent, spectroscopy-based, and scattering-based assays. Research in recent years has shown promising progress, but substantial limitations still exist due to environmental lighting interference, reliance upon proprietary smartphone attachments, and the undefined sensitivity variations between different smartphones. In this review, recent research in smartphone chemical and biosensing is assessed, and discussion is made regarding the opportunities that new research methods have to improve the scope of resource-limited sensing.

Chen H., Gao Y., Li G., Alam M., Udayakumar S., Mateen Q.N., Rostamian S., Cilley K., Kim S., Cho G., Gwak J., Song Y., Hardie J.M., Kanakasabapathy M.K., Kandula H., et. al.

Viral hepatitis remains a major global health issue, with chronic hepatitis B (HBV) and hepatitis C (HCV) causing approximately 1 million deaths annually, primarily due to liver cancer and cirrhosis. More than 1.5 million people contract HCV each year, disproportionately affecting vulnerable populations, including American Indians and Alaska Natives (AI/AN). While direct-acting antivirals (DAAs) are highly effective, timely and accurate HCV diagnosis remains a challenge, particularly in resource-limited settings. The current two-step HCV testing process is costly and time-intensive, often leading to patient loss before treatment. Point-of-care (POC) HCV antigen (Ag) testing offers a promising alternative, but no FDA-approved test meets the required sensitivity and specificity. To address this, we developed a fully automated, smartphone-based POC HCV Ag assay using platinum nanoparticles, deep learning image processing, and microfluidics. With an overall accuracy of 94.59%, this cost-effective, portable device has the potential to reduce HCV-related health disparities, particularly among AI/AN populations, improving accessibility and equity in care.

Huang P., Lan H., Liu B., Mo Y., Gao Z., Ye H., Pan T.

Li X., Liu M., Xia X., Zeng X., Men D., Duan Y., Hou J., Hou C., Huo D.

Asadian E., Bahramian F., Siavashy S., Movahedi S., Keçili R., Hussain C.M., Ghorbani-Bidkorpeh F.

Zhu C., Xun Z., Fu R., Huang Q., Ou Q., Xianyu Y., Liu C.

Li X., Liu M., Men D., Duan Y., Deng L., Zhou S., Hou J., Hou C., Huo D.

Fast, sensitive, and portable detection of genetic modification contributes to agricultural security and food safety. Here, we developed RPA-CRISPR/Cas12a-G-quadruplex colorimetric assays that can combine with intelligent recognition by deep learning algorithms to achieve sensitive, rapid, and portable detection of the CaMV35S promoter. When the crRNA-Cas12a complex recognizes the RPA amplification product, Cas12 cleaves the G-quadruplex, causing the G4-Hemin complex to lose its peroxide mimetic enzyme function and be unable to catalyze the conversion of ABTS

Zhang L., Wang H., Yang S., Liu J., Li J., Lu Y., Cheng J., Xu Y.

Chakraborty P., Doganay M.T., Tozluyurt A., Hujer A.M., Bonomo R.A., Draz M.S.

ABSTRACTAntimicrobial resistance (AMR) is one of the most challenging public health problems, and implementation of effective and accessible testing solutions is an ever-increasing unmet need. Artificial intelligence (AI) offers a promising avenue for enhanced testing performance and accuracy. We introduce an AI system specifically designed for rapid AMR testing, eliminating the requirement for bulky hardware and extensive automation. Our system incorporates a novel approach for nanotechnology-empowered intelligent diagnostics (NEIDx), leveraging nanoparticles to enable novel AI-based advanced systems for detection. We employ catalytic nanoparticle-based NEIDx coupled with magnetic separation to facilitate the direct detection of AMR-associated enzymes from blood samples. This is achieved through the formation of easily visible and detectable large bubbles, a process streamlined by AI running on a cellphone. We evaluated the performance of our AI system using two clinically relevant AMR enzymes: Klebsiella pneumoniae carbapenemase-2 (KPC-2) and Sulfhydryl variable-1 (SHV-1) β-lactamases. The system demonstrated qualitative detection with a sensitivity of 82.61% (CI of 79.7 - 85.5%) and a specificity of 92.31% (CI of 90.3 - 94.3%) in blood samples, respectively. This innovative approach holds significant promise for advancing point-of-care diagnostics and addressing the urgent need for rapid and accessible AMR testing in diverse healthcare settings.

Rasheed S., Kanwal T., Ahmad N., Fatima B., Najam-ul-Haq M., Hussain D.

Portable optical biosensors have emerged as revolutionary tools in point-of-care diagnostics, bringing the healthcare sector to the next level. Developing cutting-edge portable optical sensors represents significant advances in disease detection and monitoring. This review includes classifying optical sensors based on their transduction mechanism, addressing challenges such as sensitivity, specificity, miniaturization, cost considerations, regulatory approvals associated with portable optical biosensors for point-of-care diagnostics, and potential solutions to address these challenges. Miniaturization strategies and the importance of innovative materials and substrates in designing point-of-care diagnostic devices are investigated. The review further explores the recent advancements in miniaturization that have led to the development of portable optical devices for their recent applications in rapid point-of-care diagnostics, focusing on detecting various bioanalytes associated with various health conditions. Portable optical biosensors can revolutionize healthcare by enabling rapid, accurate, and personalized diagnoses, improving disease management, healthcare outcomes, and global diagnostic accessibility through technological advancements.

Wang H., Wang Y., Wang W., Zhang Y., Yuan Q., Tan J.

Wang C., Wang Z., Lu Y., Hao T., Hu Y., Wang S., Guo Z.

In this work, an image classification based on deep learning for quantitative field determination of aluminum ions (Al3+) was developed. Carbon quantum dots with yellow fluorescence were synthesized by a one-pot hydrothermal method which could specifically recognize Al3+ and produce enhanced green fluorescence. Using the convolutional neural network model in deep learning, an image classification was constructed to classify Al3+ samples at different concentrations. Then, a fitting method for classification information was proposed for the first time which could convert discontinuous, semi-quantitative concentration classification information into continuous, quantitative, and accurate concentration information. Recoveries of 92.0–110.3% in the concentration range of 0.3–320 μM were obtained with a lower limit of detection of 0.3 μM, exhibiting excellent accuracy and sensitivity. It could be completed in 2 min simply without requiring large equipment. Thus, the deep learning-enabled image classification paves a new way for the determination of metal ions.

Sharma K., Kesharwani P., Jain A., Mody N., Sharma G., Sharma S., Hussain C.M.

Chapter 8 Challenges and Preventive Interventions in COVID-19 Transmission through Domestic Chemistry Hygiene A Critical Assessment Kanika Sharma, Kanika Sharma Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, IndiaSearch for more papers by this authorPayal Kesharwani, Payal Kesharwani Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, IndiaSearch for more papers by this authorAnkit Jain, Ankit Jain Department of Materials Engineering, Indian Institute of Science, Bangalore, Karnataka, IndiaSearch for more papers by this authorNishi Mody, Nishi Mody Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, Madhya Pradesh, IndiaSearch for more papers by this authorGunjan Sharma, Gunjan Sharma Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, IndiaSearch for more papers by this authorSwapnil Sharma, Swapnil Sharma Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, IndiaSearch for more papers by this authorChaudhery Mustansar Hussain, Chaudhery Mustansar Hussain Department of Chemistry and EVSC, New Jersey Institute of Technology, Newark, NJ, USASearch for more papers by this author Kanika Sharma, Kanika Sharma Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, IndiaSearch for more papers by this authorPayal Kesharwani, Payal Kesharwani Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, IndiaSearch for more papers by this authorAnkit Jain, Ankit Jain Department of Materials Engineering, Indian Institute of Science, Bangalore, Karnataka, IndiaSearch for more papers by this authorNishi Mody, Nishi Mody Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, Madhya Pradesh, IndiaSearch for more papers by this authorGunjan Sharma, Gunjan Sharma Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, IndiaSearch for more papers by this authorSwapnil Sharma, Swapnil Sharma Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, IndiaSearch for more papers by this authorChaudhery Mustansar Hussain, Chaudhery Mustansar Hussain Department of Chemistry and EVSC, New Jersey Institute of Technology, Newark, NJ, USASearch for more papers by this author Book Editor(s):Deepak Rawtani, Deepak Rawtani National Forensic Sciences Univ., Gujarat, IndiaSearch for more papers by this authorChaudhery Mustansar Hussain, Chaudhery Mustansar Hussain New Jersey Inst. of Technology, U.S.ASearch for more papers by this author First published: 08 September 2023 https://doi.org/10.1002/9781119777403.ch8 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onEmailFacebookTwitterLinkedInRedditWechat Summary The threat to health and social life resulting due to the spread of SARS-CoV-2 is the leading cause of pandemic affecting millions of the population worldwide and has influenced people to maintain hygiene conditions all around. The use of toilets and bathrooms has become a controversial topic. Fecal-based transmission in COVID-19 begets from hidden colloidal bioaerosols produced after flushing the toilet, which generates turbulence expelling aerosol into the surrounding area which lands on various surfaces. The virus is found to remain suspended in the air, which can affect the person around it and also settles on various colloid surfaces, which facilitates the transmission cycle from feces to the surface to body parts and eventually to the oral and nasal cavity. Moreover, untreated wastewater is turning out to be a major key point for the spread of the virus. This review investigates risks associated with the use of the toilet by an infected person. The vulnerability of common use of the toilet in various domains at public places, hospitals, airplanes, and even at homes, along with transmission via bioaerosolization has also been focused on in this chapter. It also analyzes all the possibilities of protection and also application of design solutions such as a smart sensor to maintain hygienic and sanitized conditions. Some inexpensive interventions are also introduced to prevent transmission in personal settings. These have been brought forth to pave new horizons for impeding the transmission of COVID-19. References Atmar , R.L. , Opekun , A.R. , Gilger , M.A. et al. ( 2008 ). Norwalk virus shedding after experimental human infection . Emerging Infectious Diseases 14 ( 10 ): 1553 . 10.3201/eid1410.080117 PubMedWeb of Science®Google Scholar Bae , S.H. , Shin , H. , Koo , H.Y. et al. ( 2020 ). Asymptomatic transmission of SARS-CoV-2 on evacuation flight . Emerging Infectious Diseases 26 ( 11 ): 2705 . 10.3201/eid2611.203353 CASPubMedWeb of Science®Google Scholar Barker , J. and Bloomfield , S.F. ( 2000 ). Survival of Salmonella in bathrooms and toilets in domestic homes following salmonellosis . 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Jiang L., Liu X., Zhao D., Guo J., Ma X., Wang Y.

In this review, we delved into an elaborate exposition of different detection principles reliant on micro/nanomotors (MNMs), explore the challenges encountered by MNMs under distinct detection principles, and discuss potential future solutions.

Battalapalli D., Chakraborty P., Jain D., Obaro S.K., Gurkan U.A., Bonomo R.A., Draz M.S.

Rapid and reliable point-of-care (POC) diagnostic tests can have a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. To overcome this challenge, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes is first modified with thiolated PEG molecules, leaving the hydrazide groups available to react with the aldehyde group in the Fc fragments of the oxidized IgG antibodies. Using anti-Klebsiella pneumoniae carbapenemase-2 (KPC-2) antibody as a model antibody used for antimicrobial resistance (AMR) testing, our results demonstrate a ~10-fold increase in antibody coupling compared with the standard N-hydroxysuccinimide (NHS)-based conjugation chemistry and effective capture (>94%) of the target KPC-2 enzyme antigen on the surface of modified electrodes. This straightforward and easy-to-perform strategy of site-directed antibody conjugation can be engineered for coupling other protein- and non-protein-based biological molecules commonly used in POC testing and development, thus enhancing the potential for improved diagnostic accuracy and performance.

Arumugam S., Ma J., Macar U., Han G., McAulay K., Ingram D., Ying A., Chellani H.H., Chern T., Reilly K., Colburn D.A., Stanciu R., Duffy C., Williams A., Grys T., et. al.

Abstract Background Point-of-care diagnostic devices, such as lateral-flow assays, are becoming widely used by the public. However, efforts to ensure correct assay operation and result interpretation rely on hardware that cannot be easily scaled or image processing approaches requiring large training datasets, necessitating large numbers of tests and expert labeling with validated specimens for every new test kit format. Methods We developed a software architecture called AutoAdapt POC that integrates automated membrane extraction, self-supervised learning, and few-shot learning to automate the interpretation of POC diagnostic tests using smartphone cameras in a scalable manner. A base model pre-trained on a single LFA kit is adapted to five different COVID-19 tests (three antigen, two antibody) using just 20 labeled images. Results Here we show AutoAdapt POC to yield 99% to 100% accuracy over 726 tests (350 positive, 376 negative). In a COVID-19 drive-through study with 74 untrained users self-testing, 98% found image collection easy, and the rapidly adapted models achieved classification accuracies of 100% on both COVID-19 antigen and antibody test kits. Compared with traditional visual interpretation on 105 test kit results, the algorithm correctly identified 100% of images; without a false negative as interpreted by experts. Finally, compared to a traditional convolutional neural network trained on an HIV test kit, the algorithm showed high accuracy while requiring only 1/50th of the training images. Conclusions The study demonstrates how rapid domain adaptation in machine learning can provide quality assurance, linkage to care, and public health tracking for untrained users across diverse POC diagnostic tests.