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1.
Bioengineered ; 13(1): 876-883, 2022 01.
Article in English | MEDLINE | ID: covidwho-1585254

ABSTRACT

This research has developed a method for rapid detection of SARS-CoV-2 N protein on a paper-based microfluidic chip. The chitosan-glutaraldehyde cross-linking method is used to fix the coated antibody, and the sandwich enzyme-linked immunosorbent method is used to achieve the specific detection of the target antigen. The system studied the influence of coating antibody concentration and enzyme-labeled antibody concentration on target antigen detection. According to the average gray value measured under different N protein concentrations, the standard curve of the method was established and the sensitivity was tested, and its linear regression was obtained. The equation is y = 9.8286x+137.6, R2 = 0.9772 > 0.90, which shows a high degree of fit. When the concentration of coating antibody and enzyme-labeled antibody were 1 µg/mL and 2 µg/mL, P > 0.05, the difference was not statistically significant, so the lower concentration of 1 µg/mL was chosen as the coating antibody concentration. The results show that the minimum concentration of N protein that can be detected by this method is 8 µg/mL, and the minimum concentration of coating antibody and enzyme-labeled antibody is 1 µg/mL, which has the characteristics of high sensitivity and good repeatability.


Subject(s)
Antigens, Viral/analysis , COVID-19 Serological Testing/instrumentation , Coronavirus Nucleocapsid Proteins/analysis , Coronavirus Nucleocapsid Proteins/immunology , Lab-On-A-Chip Devices , SARS-CoV-2/chemistry , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Biomedical Engineering , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/standards , Coronavirus Nucleocapsid Proteins/standards , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Humans , Lab-On-A-Chip Devices/standards , Lab-On-A-Chip Devices/statistics & numerical data , Microchip Analytical Procedures/methods , Microchip Analytical Procedures/standards , Microchip Analytical Procedures/statistics & numerical data , Paper , Phosphoproteins/analysis , Phosphoproteins/immunology , Phosphoproteins/standards
2.
MAbs ; 13(1): 1978130, 2021.
Article in English | MEDLINE | ID: covidwho-1442969

ABSTRACT

Recent years have seen unparalleled development of microfluidic applications for antibody discovery in both academic and pharmaceutical research. Microfluidics can support native chain-paired library generation as well as direct screening of antibody secreting cells obtained by rodent immunization or from the human peripheral blood. While broad diversities of neutralizing antibodies against infectious diseases such as HIV, Ebola, or COVID-19 have been identified from convalescent individuals, microfluidics can expedite therapeutic antibody discovery for cancer or immunological disease indications. In this study, a commercially available microfluidic device, Cyto-Mine, was used for the rapid identification of natively paired antibodies from rodents or human donors screened for specific binding to recombinant antigens, for direct screening with cells expressing the target of interest, and, to our knowledge for the first time, for direct broad functional IgG antibody screening in droplets. The process time from cell preparation to confirmed recombinant antibodies was four weeks. Application of this or similar microfluidic devices and methodologies can accelerate and enhance pharmaceutical antibody hit discovery.


Subject(s)
Antibodies, Neutralizing/isolation & purification , Immunoglobulin G/isolation & purification , Microfluidics/methods , Animals , Antibodies, Bacterial/immunology , Antibodies, Bacterial/isolation & purification , Antibodies, Monoclonal/isolation & purification , Antibodies, Viral/isolation & purification , Antibody Specificity , Antigens/immunology , Antigens, Neoplasm/immunology , Blood Preservation , COVID-19/immunology , Fluorescence Resonance Energy Transfer , Humans , Hybridomas/immunology , Immunomagnetic Separation , Lab-On-A-Chip Devices , Mice , Microfluidics/instrumentation , Muromonab-CD3/immunology , Plasma Cells , Recombinant Proteins/immunology , SARS-CoV-2/immunology , Tetanus Toxoid/immunology , Vaccination
3.
Lab Chip ; 21(12): 2330-2332, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1415964

ABSTRACT

The search for antibody therapeutic candidates is a timely and important challenge well-suited to lab on a chip approaches. Vancouver-based AbCellera Biologics Inc. developed a microfluidic antibody screening platform, ancillary technologies, and a service-based drug discovery business model that has proved a tremendous success. We take the opportunity here to reflect on what enabled this success. We consider the common lab on a chip motivations that were part of their success, and those that were not.


Subject(s)
Biological Products , Microfluidic Analytical Techniques , Drug Discovery , Lab-On-A-Chip Devices , Microfluidics
4.
Microbiol Spectr ; 9(2): e0025721, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1410327

ABSTRACT

Human-to-human transmission of viruses, such as influenza viruses and coronaviruses, can promote virus evolution and the emergence of new strains with increased potential for creating pandemics. Clinical studies analyzing how a particular type of virus progressively evolves new traits, such as resistance to antiviral therapies, as a result of passing between different human hosts are difficult to carry out because of the complexity, scale, and cost of the challenge. Here, we demonstrate that spontaneous evolution of influenza A virus through both mutation and gene reassortment can be reconstituted in vitro by sequentially passaging infected mucus droplets between multiple human lung airway-on-a-chip microfluidic culture devices (airway chips). Modeling human-to-human transmission of influenza virus infection on chips in the continued presence of the antiviral drugs amantadine or oseltamivir led to the spontaneous emergence of clinically prevalent resistance mutations, and strains that were resistant to both drugs were identified when they were administered in combination. In contrast, we found that nafamostat, an inhibitor targeting host serine proteases, did not induce viral resistance. This human preclinical model may be useful for studying viral evolution in vitro and identifying potential influenza virus variants before they appear in human populations, thereby enabling preemptive design of new and more effective vaccines and therapeutics. IMPORTANCE The rapid evolution of viruses, such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging the use and development of antivirals and vaccines. Studies of within-host viral evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape viral global evolution as well as development of better antivirals and vaccines. However, little is known about how viral evolution of resistance to antivirals occurs clinically due to the lack of preclinical models that can faithfully model influenza infection in humans. Our study shows that influenza viral evolution through mutation or gene reassortment can be recapitulated in a human lung airway-on-a-chip (airway chip) microfluidic culture device that can faithfully recapitulate the influenza infection in vitro. This approach is useful for studying within-host viral evolution, evaluating viral drug resistance, and identifying potential influenza virus variants before they appear in human populations, thereby enabling the preemptive design of new and more effective vaccines and therapeutics.


Subject(s)
Drug Resistance, Viral/genetics , Evolution, Molecular , Influenza A virus/drug effects , Influenza A virus/genetics , Lab-On-A-Chip Devices , Amantadine/pharmacology , Antiviral Agents/pharmacology , Benzamidines/pharmacology , Guanidines/pharmacology , Humans , Influenza, Human/drug therapy , Influenza, Human/transmission , Lung/virology , Microfluidics , Oseltamivir/pharmacology , SARS-CoV-2/genetics
5.
Acc Chem Res ; 54(19): 3643-3655, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1404866

ABSTRACT

Reliable, inexpensive, and rapid diagnostic tools are essential to control and prevent the spread of infectious diseases. Many commercial kits for coronavirus disease 2019 (COVID-19) diagnostics have played a crucial role in the fight against the COVID-19 pandemic. Most current standard in vitro diagnostic (IVD) protocols for infectious diseases are sensitive but time-consuming and require sophisticated laboratory equipment and specially trained personnel. Recent advances in biosensor technology suggest the potential to deliver point-of-care (POC) diagnostics that are affordable and provide accurate results in a short time. The ideal "sample-in-answer-out" type fully integrated POC infection diagnostic platforms are expected to be autonomous or easy-to-operate, equipment-free or infrastructure-independent, and high-throughput or easy to upscale. In this Account, we detail the recent progress made by our group and others in the development of centrifugal microfluidic devices or lab-on-a-disc (LOAD) systems. Unlike conventional pump-based fluid actuation, the centrifugal force generated by spinning the disc induces liquid pumping and no external fluidic interconnects are required. This allows a total fluidic network required for multiple steps of biological assays to be integrated on a disc, enabling fully automated POC diagnostics. Various applications have been demonstrated, including liquid biopsy for personalized cancer management, food applications, and environmental monitoring; here, we focus on IVD for infectious disease. First, we introduce various on-disc unit operation technologies, including reagent storage, sedimentation, filtration, valving, decanting, aliquoting, mixing, separation, serial dilution, washing, and calibration. Such centrifugal microfluidic technologies have already proved promising for micro-total-analysis systems for automated IVD ranging from molecular detection of pathogens to multiplexed enzyme-linked immunosorbent assays (ELISAs) that use raw samples such as whole blood or saliva. Some recent examples of LOAD systems for molecular diagnostics in which some or all steps of the assays are integrated on a disc, including pathogen enrichment, nucleic acid extraction, amplification, and detection, are discussed in detail. We then introduce fully automated ELISA systems with enhanced sensitivity. Furthermore, we demonstrate a toy-inspired fidget spinner that enables electricity-free and rapid analysis of pathogens from undiluted urine samples of patients with urinary tract infection symptoms and a phenotypic antimicrobial susceptibility test for an extreme POC diagnostics application. Considering the urgent need for cost-effective and reliable POC infection diagnostic tools, especially in the current pandemic crisis, the current limitations and future directions of fast and broad adaptation in real-world settings are also discussed. With proper attention to key challenges and leverage with recent advances in bio-sensing technologies, molecular biology, nanomaterials, analytical chemistry, miniaturization, system integration, and data management, LOAD systems hold the potential to deliver POC infection diagnostic tools with unprecedented performance regarding time, accuracy, and cost. We hope the new insight and promise of LOAD systems for POC infection diagnostics presented in this Account can spark new ideas and inspire further research and development to create better healthcare systems for current and future pandemics.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Point-of-Care Systems , Biosensing Techniques/methods , COVID-19/virology , COVID-19 Testing/instrumentation , Centrifugation , Humans , Lab-On-A-Chip Devices , RNA, Viral/analysis , RNA, Viral/isolation & purification , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
6.
Int J Mol Sci ; 22(3)2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1389389

ABSTRACT

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients' CNS and serve as a platform for therapeutic development and personalized precision medicine.


Subject(s)
Central Nervous System Diseases/drug therapy , Drug Discovery/methods , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Tissue Engineering/methods , Animals , COVID-19/drug therapy , COVID-19/pathology , Central Nervous System Diseases/pathology , Drug Discovery/instrumentation , Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Humans , Induced Pluripotent Stem Cells/pathology , Lab-On-A-Chip Devices , Organoids/cytology , Organoids/drug effects , Organoids/pathology , Tissue Engineering/instrumentation , Zika Virus Infection/drug therapy , Zika Virus Infection/pathology
7.
Cells ; 10(7)2021 06 26.
Article in English | MEDLINE | ID: covidwho-1389304

ABSTRACT

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.


Subject(s)
Lab-On-A-Chip Devices , Lung Diseases/pathology , Lung/physiology , Regeneration/physiology , Respiratory Mucosa/cytology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Cells, Cultured , Extracellular Matrix/physiology , Humans , Lung/cytology , Lung/pathology , Lung Diseases/physiopathology , Lung Diseases/therapy , Models, Biological , Respiratory Mucosa/pathology , Respiratory Mucosa/physiology , SARS-CoV-2/pathogenicity , Tissue Culture Techniques/instrumentation , Tissue Culture Techniques/methods
8.
Acc Chem Res ; 54(18): 3550-3562, 2021 09 21.
Article in English | MEDLINE | ID: covidwho-1377906

ABSTRACT

Infectious diseases present tremendous challenges to human progress and public health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) pandemic continue to pose an imminent threat to humanity. These infectious diseases highlight the importance of developing innovative strategies to study disease pathogenesis and protect human health. Although conventional in vitro cell culture and animal models are useful in facilitating the development of effective therapeutics for infectious diseases, models that can accurately reflect human physiology and human-relevant responses to pathogens are still lacking. Microfluidic organs-on-a-chip (organ chips) are engineered microfluidic cell culture devices lined with living cells, which can resemble organ-level physiology with high fidelity by rebuilding tissue-tissue interfaces, mechanical cues, fluidic flow, and the biochemical cellular microenvironment. They present a unique opportunity to bridge the gap between in vitro experimental models and in vivo human pathophysiology and are thus a promising platform for disease studies and drug testing. In this Account, we first introduce how recent progress in organ chips has enabled the recreation of complex pathophysiological features of human infections in vitro. Next, we describe the progress made by our group in adopting organ chips and other microphysiological systems for the study of infectious diseases, including SARS-CoV-2 viral infections and intrauterine bacterial infections. Respiratory symptoms dominate the clinical manifestations of many COVID-19 patients, even involving the systemic injury of many distinct organs, such as the lung, the gastrointestinal tract, and so forth. We thus particularly highlight our recent efforts to explore how lung-on-a-chip and intestine-on-a-chip might be useful in addressing the ongoing viral pandemic of COVID-19 caused by SARS-CoV-2. These organ chips offer a potential platform for studying virus-host interactions and human-relevant responses as well as accelerating the development of effective therapeutics against COVID-19. Finally, we discuss opportunities and challenges in the development of next-generation organ chips, which are urgently needed for developing effective and affordable therapies to combat infectious diseases. We hope that this Account will promote awareness about in vitro organ microphysiological systems for modeling infections and stimulate joint efforts across multiple disciplines to understand emerging and re-emerging pandemic diseases and rapidly identify innovative interventions.


Subject(s)
Bacterial Infections/diagnosis , COVID-19/diagnosis , Lab-On-A-Chip Devices , Humans
9.
Anal Chem ; 93(35): 11956-11964, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1368898

ABSTRACT

Coronavirus diseases such as the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose serious threats. Portable and accurate nucleic acid detection is still an urgent need to achieve on-site virus screening and timely infection control. Herein, we have developed an on-site, semiautomatic detection system, aiming at simultaneously overcoming the shortcomings suffered by various commercially available assays, such as low accuracy, poor portability, instrument dependency, and labor intensity. Ultrasensitive isothermal amplification [i.e., reverse transcription loop-mediated isothermal amplification (RT-LAMP)] was applied to generate intensified SARS-CoV-2 RNA signals, which were then transduced to portable commercial pregnancy test strips (PTSs) via ultraspecific human chorionic gonadotropin (hCG)-conjugated toehold-mediated strand exchange (TMSE) probes (hCG-P). The entire detection was integrated into a four-channel, palm-size microfluidic device, named the microfluidic point-of-care (POC) diagnosis system based on the PTS (MPSP) detection system. It provides rapid, cost-effective, and sensitive detection, of which the lowest concentration of detection was 0.5 copy/µL of SARS-CoV-2 RNA, regardless of the presence of other similar viruses, even highly similar severe acute respiratory syndrome coronavirus (SARS-CoV). The successful detection of the authentic samples from different resources evaluated the practical application. The commercial PTS provides a colorimetric visible signal, which is instrument- and optimization-free. Therefore, this MPSP system can be immediately used for SARS-CoV-2 emergency detection, and it is worthy of further optimization to achieve full automation and detection for other infectious diseases.


Subject(s)
COVID-19 , Pregnancy Tests , Female , Humans , Lab-On-A-Chip Devices , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Point-of-Care Systems , Pregnancy , RNA, Viral/genetics , SARS-CoV-2 , Sensitivity and Specificity
10.
Anal Bioanal Chem ; 413(7): 1787-1798, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1336052

ABSTRACT

Rapid and accurate identification of respiratory tract infection pathogens is of utmost importance for clinical diagnosis and treatment, as well as prevention of pathogen transmission. To meet this demand, a microfluidic chip-based PCR-array system, Onestart, was developed. The Onestart system uses a microfluidic chip packaged with all the reagents required, and the waste liquid is also collected and stored on the chip. This ready-to-use system can complete the detection of 21 pathogens in a fully integrated manner, with sample lysis, nucleic acid extraction/purification, and real-time PCR sequentially implemented on the same chip. The entire analysis process is completed within 1.5 h, and the system automatically generates a test report. The lower limit-of-detection (LOD) of the Onestart assay was determined to be 1.0 × 103 copies·mL-1. The inter-batch variation of cycle threshold (Ct) values ranged from 0.08% to 0.69%, and the intra-batch variation ranged from 0.9% to 2.66%. Analytical results of the reference sample mix showed a 100% specificity of the Onestart assay. The analysis of batched clinical samples showed consistency of the Onestart assay with real-time PCR. With its ability to provide rapid, sensitive, and specific detection of respiratory tract infection pathogens, application of the Onestart system will facilitate timely clinical management of respiratory tract infections and effective prevention of pathogen transmission. Onestart, a ready-to-use system, can detect 21 pathogens in a fully integrated manner on a microchip within 1.5 h.


Subject(s)
Automation , Polymerase Chain Reaction/methods , Respiratory Tract Infections/diagnosis , COVID-19 Testing/methods , Diagnosis, Computer-Assisted , Equipment Design , Humans , Lab-On-A-Chip Devices , Limit of Detection , Microfluidic Analytical Techniques/methods , Microfluidics , Pattern Recognition, Automated , Quality Control , RNA, Viral/analysis , Reproducibility of Results , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/virology , SARS-CoV-2 , Sensitivity and Specificity , Viruses
11.
Biosensors (Basel) ; 11(7)2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1323110

ABSTRACT

Optofluidic flow-through biosensors are being developed for single particle detection, particularly as a tool for pathogen diagnosis. The sensitivity of the biosensor chip depends on design parameters, illumination format (side vs. top), and flow configuration (parabolic, two- and three-dimensional hydrodynamic focused (2DHF and 3DHF)). We study the signal differences between various combinations of these design aspects. Our model is validated against a sample of physical devices. We find that side-illumination with 3DHF produces the strongest and consistent signal, but parabolic flow devices process a sample volume more quickly. Practical matters of optical alignment are also discussed, which may affect design choice.


Subject(s)
Biosensing Techniques/instrumentation , Lab-On-A-Chip Devices , Hydrodynamics , Microfluidic Analytical Techniques
12.
Talanta ; 235: 122733, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1322356

ABSTRACT

The microfluidic paper-based analytical devices (µPADs) have grown-up swiftly over the decade due to its low cost, simple fabrication procedure, resource-limitedness, non-toxicity and their environmentally benign nature. The µPADs, also identified as point-of-care devices or health care devices have successfully applied in several fields such as diagnostics, biological, food safety, environmental, electrochemical and most importantly colorimetric/fluorimetric sensors, owing to the attractive passive motions of analyte without any external forces. In recent years, a large number of colorimetric and fluorimetric probes have been reported that can selectively recognize the analytes in µPADs. However, there is no organized review on its structure-activity relationship. In this review, we have focused to summarize the colorimetric and fluorimetric probes utilized in µPADs. This review discuss about the relationships between the structure and functions of various probes as signaling units of the efficient µPADs. The probes including nanomaterials, nanozymes, polymers and organic molecules, their structural activity with regard to sensing performances along with their limit of detection are also discussed. This review is expected to assist readers for better understanding of the sensing mechanisms of various chemo and bio-probes utilized in µPADs, as well as promote their advancement in the field. On the other hand, this review also helps the researchers for enhancement of µPADs and paves way for synergistic application of existing molecular probes as an effective diagnostic tool for the worldwide pandemic novel corona virus COVID-19.


Subject(s)
COVID-19 , Microfluidic Analytical Techniques , Humans , Lab-On-A-Chip Devices , Microfluidics , Paper , SARS-CoV-2
13.
ACS Sens ; 6(7): 2709-2719, 2021 07 23.
Article in English | MEDLINE | ID: covidwho-1310777

ABSTRACT

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.


Subject(s)
COVID-19 Testing , COVID-19 , Enzyme-Linked Immunosorbent Assay , Lab-On-A-Chip Devices , Antibodies, Viral/blood , COVID-19/diagnosis , Humans , SARS-CoV-2 , Sensitivity and Specificity
14.
Molecules ; 25(20)2020 Oct 13.
Article in English | MEDLINE | ID: covidwho-1305732

ABSTRACT

Nano-islands are entities (droplets or other shapes) that are formed by spontaneous dewetting (agglomeration, in the early literature) of thin and very thin metallic (especially gold) films on a substrate, done by post-deposition heating or by using other sources of energy. In addition to thermally generated nano-islands, more recently, nanoparticle films have also been dewetted, in order to form nano-islands. The localized surface plasmon resonance (LSPR) band of gold nano-islands was found to be sensitive to changes in the surrounding environment, making it a suitable platform for sensing and biosensing applications. In this review, we revisit the development of the concept of nano-island(s), the thermodynamics of dewetting of thin metal films, and the effect of the substrate on the morphology and optical properties of nano-islands. A special emphasis is made on nanoparticle films and their applications to biosensing, with ample examples from the authors' work.


Subject(s)
Gold/chemistry , Nanocomposites/chemistry , Point-of-Care Systems , Surface Plasmon Resonance/instrumentation , Animals , Biosensing Techniques/instrumentation , Growth Hormone/analysis , Humans , Lab-On-A-Chip Devices , Milk/chemistry , Nanotechnology/methods , Surface Plasmon Resonance/methods
15.
IEEE Pulse ; 12(3): 6-10, 2021.
Article in English | MEDLINE | ID: covidwho-1280249

ABSTRACT

The novel coronavirus is a new kind of enemy. Now, the United States Army has added a cutting-edge tool to its arsenal to better understand this threat: "organs-on-chips" that recapitulate the microarchitecture and function of living human lungs.


Subject(s)
COVID-19/metabolism , Lab-On-A-Chip Devices , Lung/metabolism , SARS-CoV-2/metabolism , Tissue Array Analysis , COVID-19/therapy , Humans
16.
Anal Chim Acta ; 1177: 338758, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1267550

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the unprecedented global pandemic of coronavirus disease-2019 (COVID-19). Efforts are needed to develop rapid and accurate diagnostic tools for extensive testing, allowing for effective containment of the infection via timely identification and isolation of SARS-CoV-2 carriers. Current gold standard nucleic acid tests require many separate steps that need trained personnel to operate specialist instrumentation in laboratory environments, hampering turnaround time and test accessibility, especially in low-resource settings. We devised an integrated on-chip platform coupling RNA extraction based on immiscible filtration assisted by surface tension (IFAST), with RNA amplification and detection via colorimetric reverse-transcription loop mediated isothermal amplification (RT-LAMP), using two sets of primers targeting open reading frame 1a (ORF1a) and nucleoprotein (N) genes of SARS-CoV-2. Results were identified visually, with a colour change from pink to yellow indicating positive amplification, and further confirmed by DNA gel electrophoresis. The specificity of the assay was tested against HCoV-OC43 and H1N1 RNAs. The assay based on use of gene N primers was 100% specific to SARS-CoV-2 with no cross-reactivity to HCoV-OC43 nor H1N1. Proof-of-concept studies on water and artificial sputum containing genomic SARS-CoV-2 RNA showed our IFAST RT-LAMP device to be capable of extracting and detecting 470 SARS-CoV-2 copies mL-1 within 1 h (from sample-in to answer-out). IFAST RT-LAMP is a simple-to-use, integrated, rapid and accurate COVID-19 diagnostic platform, which could provide an attractive means for extensive screening of SARS-CoV-2 infections at point-of-care, especially in resource-constrained settings.


Subject(s)
COVID-19 , Lab-On-A-Chip Devices , RNA, Viral , COVID-19/diagnosis , Humans , Influenza A Virus, H1N1 Subtype , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , RNA, Viral/isolation & purification , SARS-CoV-2 , Sensitivity and Specificity
17.
ACS Sens ; 6(6): 2108-2124, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1253892

ABSTRACT

Readily deployable, low-cost point-of-care medical devices such as lateral flow assays (LFAs), microfluidic paper-based analytical devices (µPADs), and microfluidic thread-based analytical devices (µTADs) are urgently needed in resource-poor settings. Governed by the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverability) set by the World Health Organization, these reliable platforms can screen a myriad of chemical and biological analytes including viruses, bacteria, proteins, electrolytes, and narcotics. The Ebola epidemic in 2014 and the ongoing pandemic of SARS-CoV-2 have exemplified the ever-increasing importance of timely diagnostics to limit the spread of diseases. This review provides a comprehensive survey of LFAs, µPADs, and µTADs that can be deployed in resource-limited settings. The subsequent commercialization of these technologies will benefit the public health, especially in areas where access to healthcare is limited.


Subject(s)
COVID-19 , Point-of-Care Systems , Biological Assay , Humans , Lab-On-A-Chip Devices , SARS-CoV-2
18.
ACS Nano ; 15(6): 10194-10202, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1233686

ABSTRACT

Advent and fast spread of pandemic diseases draw worldwide attention to rapid, prompt, and accurate molecular diagnostics with technical development of ultrafast polymerase chain reaction (PCR). Microfluidic on-chip PCR platforms provide highly efficient and small-volume bioassay for point-of-care diagnostic applications. Here we report ultrafast, real-time, and on-chip nanoplasmonic PCR for rapid and quantitative molecular diagnostics at point-of-care level. The plasmofluidic PCR chip comprises glass nanopillar arrays with Au nanoislands and gas-permeable microfluidic channels, which contain reaction microchamber arrays, a precharged vacuum cell, and a vapor barrier. The on-chip configuration allows both spontaneous sample loading and microbubble-free PCR reaction during which the plasmonic nanopillar arrays result in ultrafast photothermal cycling. After rapid sample loading less than 3 min, two-step PCR results for 40 cycles show rapid amplification in 264 s for lambda-DNA, and 306 s for plasmids expressing SARS-CoV-2 envelope protein. In addition, the in situ cyclic real-time quantification of amplicons clearly demonstrates the amplification efficiencies of more than 91%. This PCR platform can provide rapid point-of-care molecular diagnostics in helping slow the fast-spreading pandemic.


Subject(s)
COVID-19 , Lab-On-A-Chip Devices , Humans , Pathology, Molecular , Real-Time Polymerase Chain Reaction , SARS-CoV-2
19.
Anal Bioanal Chem ; 413(22): 5619-5632, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1226211

ABSTRACT

In the face of the COVID-19 pandemic, the need for rapid serological tests that allow multiplexing emerged, as antibody seropositivity can instruct about individual immunity after an infection with SARS-CoV-2 or after vaccination. As many commercial antibody tests are either time-consuming or tend to produce false negative or false positive results when only one antigen is considered, we developed an automated, flow-based chemiluminescence microarray immunoassay (CL-MIA) that allows for the detection of IgG antibodies to SARS-CoV-2 receptor-binding domain (RBD), spike protein (S1 fragment), and nucleocapsid protein (N) in human serum and plasma in less than 8 min. The CoVRapid CL-MIA was tested with a set of 65 SARS-CoV-2 serology positive or negative samples, resulting in 100% diagnostic specificity and 100% diagnostic sensitivity, thus even outcompeting commercial tests run on the same sample set. Additionally, the prospect of future quantitative assessments (i.e., quantifying the level of antibodies) was demonstrated. Due to the fully automated process, the test can easily be operated in hospitals, medical practices, or vaccination centers, offering a valuable tool for COVID-19 serosurveillance. Graphical abstract.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Immunoassay/methods , Immunoglobulin G/blood , SARS-CoV-2/immunology , Antigens, Viral/chemistry , Antigens, Viral/immunology , Automation, Laboratory , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/immunology , Immune Sera , Immunoassay/instrumentation , Lab-On-A-Chip Devices , Luminescent Measurements , Phosphoproteins/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Time Factors
20.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Article in English | MEDLINE | ID: covidwho-1216492

ABSTRACT

The urgency for the development of a sensitive, specific, and rapid point-of-care diagnostic test has deepened during the ongoing COVID-19 pandemic. Here, we introduce an ultrasensitive chip-based antigen test with single protein biomarker sensitivity for the differentiated detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A antigens in nasopharyngeal swab samples at diagnostically relevant concentrations. The single-antigen assay is enabled by synthesizing a brightly fluorescent reporter probe, which is incorporated into a bead-based solid-phase extraction assay centered on an antibody sandwich protocol for the capture of target antigens. After optimization of the probe release for detection using ultraviolet light, the full assay is validated with both SARS-CoV-2 and influenza A antigens from clinical nasopharyngeal swab samples (PCR-negative spiked with target antigens). Spectrally multiplexed detection of both targets is implemented by multispot excitation on a multimode interference waveguide platform, and detection at 30 ng/mL with single-antigen sensitivity is reported.


Subject(s)
Antigens, Viral/isolation & purification , Influenza A virus/isolation & purification , Microfluidic Analytical Techniques/methods , Molecular Diagnostic Techniques/methods , SARS-CoV-2/isolation & purification , Antigens, Viral/immunology , Biosensing Techniques , COVID-19/diagnosis , Fluorescence , Humans , Influenza A virus/immunology , Influenza, Human/diagnosis , Lab-On-A-Chip Devices , Limit of Detection , Nasopharynx/virology , Point-of-Care Systems , SARS-CoV-2/immunology
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