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1.
35th IEEE International Conference on Micro Electro Mechanical Systems Conference (IEEE MEMS) ; : 365-368, 2022.
Article in English | Web of Science | ID: covidwho-1822038

ABSTRACT

This study presents a facile route to fabricate a novel kind of digital microfluidic (DMF) chip via direct ink writing. The manufacture of this device does not rely on conventional microfabrication processes and cleanrooms, which makes it easy to prepare and low cost. By measuring the change of contact angle (CA) and droplet velocity, we proved that it could perform droplet manipulation like traditional DMF chips. In addition, after optimizing the chip structure, through a peripheral support circuit, polymerase chain reaction (PCR) reagents could be automatically partitioned and mixed on the chip. Furthermore, we realized the multi-target end-point fluorescence detection of SARS-CoV-2 RNA on this chip, showing promising potential for automatic nucleic acid tests.

2.
ACS Appl Bio Mater ; 2022.
Article in English | PubMed | ID: covidwho-1815472

ABSTRACT

Recent advances in microfluidics-based point-of-care testing (POCT) technology such as paper, array, and beads have shown promising results for diagnosing various infectious diseases. The fast and timely detection of viral infection has proven to be a critical step for deciding the therapeutic outcome in the current COVID-19 pandemic, which in turn not only enhances the patient survival rate but also reduces the disease-associated comorbidities. In the present scenario, rapid, noninvasive detection of the virus using low cost and high throughput microfluidics-based POCT devices embraces the advantages over existing diagnostic technologies, for which a centralized lab facility, expensive instruments, sample pretreatment, and skilled personnel are required. Microfluidic-based multiplexed POCT devices can be a boon for clinical diagnosis in developing countries that lacks a centralized health care system and resources. The microfluidic devices can be used for disease diagnosis and exploited for the development and testing of drug efficacy for disease treatment in model systems. The havoc created by the second wave of COVID-19 led several countries' governments to the back front. The lack of diagnostic kits, medical devices, and human resources created a huge demand for a technology that can be remotely operated with single touch and data that can be analyzed on a phone. Recent advancements in information technology and the use of smartphones led to a paradigm shift in the development of diagnostic devices, which can be explored to deal with the current pandemic situation. This review sheds light on various approaches for the development of cost-effective microfluidics POCT devices. The successfully used microfluidic devices for COVID-19 detection under clinical settings along with their pros and cons have been discussed here. Further, the integration of microfluidic devices with smartphones and wireless network systems using the Internet-of-things will enable readers for manufacturing advanced POCT devices for remote disease management in low resource settings.

3.
Advanced Nanobiomed Research ; 2(2):17, 2022.
Article in English | Web of Science | ID: covidwho-1813459

ABSTRACT

Lipid nanoparticles have attracted significant interests in the last two decades, and have achieved tremendous clinical success since the first clinical approval of Doxil in 1995. At the same time, lipid nanoparticles have also demonstrated enormous potential in delivering nucleic acid drugs as evidenced by the approval of two RNA therapies and mRNA COVID-19 vaccines. In this review, an overview on different classes of lipid nanoparticles, including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, is first provided, followed by the introduction of their preparation methods. Then the characterizations of lipid nanoparticles are briefly reviewed and their applications in encapsulating and delivering hydrophobic drugs, hydrophilic drugs, and RNAs are highlighted. Finally, various applications of lipid nanoparticles for overcoming different delivery challenges, including crossing the blood-brain barrier, targeted delivery, and various routes of administration, are summarized. Lipid nanoparticles as drug delivery systems offer many attractive benefits such as great biocompatibility, ease of preparation, feasibility of scale-up, nontoxicity, and targeted delivery, while current challenges in drug delivery warrant future studies about structure-function correlations, large-scale production, and targeted delivery to realize the full potential of lipid nanoparticles for wider clinical and pharmaceutical applications in future.

4.
Micromachines ; 13(4):499, 2022.
Article in English | ProQuest Central | ID: covidwho-1810026

ABSTRACT

Plastic pollution has emerged as a growing concern worldwide. In particular, the most abundant plastic debris, microplastics, has necessitated the development of rapid and effective identification methods to track down the stages and evidence of the pollution. In this paper, we combine low-cost plastic staining technologies using Nile Red with the continuous feature offered by microfluidics to propose a low-cost 3D printed device for the identification of microplastics. It is observed that the microfluidic devices indicate comparable staining and identification performance compared to conventional Nile Red staining processes while offering the advantages of continuous recognition for long-term environmental monitoring. The results also show that concentration, temperature, and residency time possess strong effects on the identification performance. Finally, various microplastics have been applied to further demonstrate the effectiveness of the proposed devices. It is found that, among different types of microplastics, non-spherical microplastics show the maximal fluorescence level. Meanwhile, natural fibers indicate better staining quality when compared to synthetic ones.

5.
PNAS Nexus ; 1(1):pgac028, 2022.
Article in English | PubMed | ID: covidwho-1806566

ABSTRACT

Saliva specimens have drawn interest for diagnosing respiratory viral infections due to their ease of collection and decreased risk to healthcare providers. However, rapid and sensitive immunoassays have not yet been satisfactorily demonstrated for such specimens due to their viscosity and low viral loads. Using paper microfluidic chips and a smartphone-based fluorescence microscope, we developed a highly sensitive, low-cost immunofluorescence particulometric SARS-CoV-2 assay from clinical saline gargle samples. We demonstrated the limit of detection of 10 ag/μL. With easy-to-collect saline gargle samples, our clinical sensitivity, specificity, and accuracy were 100%, 86%, and 93%, respectively, for n = 27 human subjects with n = 13 RT-qPCR positives.

6.
Lab on a Chip - Miniaturisation for Chemistry & Biology ; 22(8):1469-1473, 2022.
Article in English | Academic Search Complete | ID: covidwho-1805673

ABSTRACT

The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion. Mesa Biotech (San Diego, CA) originally developed the Accula platform for the diagnosis of influenza A and B and then extended the platform to SARS-CoV-2. Mesa Biotech has experienced tremendous success, culminating in acquisition by Thermo Fisher for up to $550m USD. The Accula microfluidics platform accomplished the leap from the lab to commercial product through clever design and engineering choices. Through information obtained from interviews with key Mesa Biotech leaders and publicly-available documents, we describe the keys to Mesa's success and how they might inform other lab-on-a-chip companies. [ FROM AUTHOR] Copyright of Lab on a Chip - Miniaturisation for Chemistry & Biology is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

7.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-333271

ABSTRACT

We assessed the affinities of the therapeutic monoclonal antibodies (mAbs) cilgavimab, tixagevimab, sotrovimab, casirivimab, and imdevimab to the receptor binding domain (RBD) of wild type, Delta, and Omicron spike. The Omicron RBD affinities of cilgavimab, tixagevimab, casirivimab, and imdevimab decreased by at least two orders of magnitude relative to their wild type equivalents, whereas sotrovimab binding was less severely impacted. These affinity reductions correlate with reduced antiviral activities of these antibodies, suggesting that simple affinity measurements can serve as an indicator for activity before challenging and time-consuming virus neutralization assays are performed. We also compared the properties of these antibodies to serological fingerprints (affinities and concentrations) of wild type RBD specific antibodies in 74 convalescent sera. The affinities of the therapeutic mAbs to wild type and Delta RBD were in the same range as the polyclonal response in the convalescent sera indicative of their high antiviral activities against these variants. However, for Omicron RBD, only sotrovimab retained affinities that were within the range of the polyclonal response, in agreement with its high activity against Omicron. Serological fingerprints thus provide important context to affinities and antiviral activity of mAb drugs and could guide the development of new therapeutics.

8.
3rd IEEE International Conference on Circuits and Systems, ICCS 2021 ; : 59-63, 2021.
Article in English | Scopus | ID: covidwho-1774639

ABSTRACT

The analysis of dielectric properties in Novel Coronavirus (COVID-19) has become an important research branch since the outbreak of the epidemic in 2019. In order to detect the dielectric properties of microfluidics like virus with higher sensitivity, a radio frequency sensor model is proposed in this paper. First, based on the excellent characteristics of the microstrip meander-line such as more concentrated electric field distribution, the microstrip meander-line is introduced into the design of traditional cancellation sensor, which is called the meander sensor. Then, the relationship between transmission coefficients of the system and dielectric properties of microfluidics is given in this paper. The simulation results verify the ultra-sensitivity of the meander sensor. Even though the relative permittivity of microfluidics is changed in the order of magnitude 10-2, the measurement results of the meander sensor also change significantly. However, the straight sensor can only measure changes of relative permittivity in the order of magnitude 10-1. What's more, there is a more concentrated measurement range for the meander sensor. This will be more practical for measuring weak changes of dielectric properties caused by the microfluidics itself and its interactions. © 2021 IEEE.

9.
ACS Infect Dis ; 8(4): 790-799, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1768765

ABSTRACT

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Affinity , Humans , Microfluidics , Spike Glycoprotein, Coronavirus
10.
Adv Drug Deliv Rev ; 184: 114197, 2022 Mar 12.
Article in English | MEDLINE | ID: covidwho-1763526

ABSTRACT

Gene therapy has emerged as a potential platform for treating several dreaded and rare diseases that would not have been possible with traditional therapies. Viral vectors have been widely explored as a key platform for gene therapy due to their ability to efficiently transport nucleic acid-based therapeutics into the cells. However, the lack of precision in their delivery has led to several off-target toxicities. As such, various strategies in the form of non-viral gene delivery vehicles have been explored and are currenlty employed in several therapies including the SARS-CoV-2 vaccine. In this review, we discuss the opportunities lipid nanoparticles (LNPs) present for efficient gene delivery. We also discuss various synthesis strategies via microfluidics for high throughput fabrication of non-viral gene delivery vehicles. We conclude with the recent applications and clinical trials of these vehicles for the delivery of different genetic materials such as CRISPR editors and RNA for different medical conditions ranging from cancer to rare diseases.

11.
Clinics in Laboratory Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1729644
12.
ACS Sens ; 7(3): 884-892, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1721394

ABSTRACT

Microfluidic paper-based analytical devices (µPADs) have experienced an unprecedented story of success. In particular, as of today, most people have likely come into contact with one of their two most famous examples─the pregnancy or the SARS-CoV-2 antigen test. However, their sensing performance is constrained by the optical readout of nanoparticle agglomeration, which typically allows only qualitative measurements. In contrast, single-impact electrochemistry offers the possibility to quantify species concentrations beyond the pM range by resolving collisions of individual species on a microelectrode. Within this work, we investigate the integration of stochastic sensing into a µPAD design by combining a wax-patterned microchannel with a microelectrode array to detect silver nanoparticles (AgNPs) by their oxidative dissolution. In doing so, we demonstrate the possibility to resolve individual nanoparticle collisions in a reference-on-chip configuration. To simulate a lateral flow architecture, we flush previously dried AgNPs along a microchannel toward the electrode array, where we are able to record nanoparticle impacts. Consequently, single-impact electrochemistry poses a promising candidate to extend the limits of lateral flow-based sensors beyond current applications toward a fast and reliable detection of very dilute species on site.


Subject(s)
COVID-19 , Metal Nanoparticles , Electrochemistry , Female , Humans , Microelectrodes , Microfluidics , Pregnancy , SARS-CoV-2 , Silver
13.
Applied Sciences ; 12(4):2198, 2022.
Article in English | ProQuest Central | ID: covidwho-1706204

ABSTRACT

Featured ApplicationMicrofluidics device for rapid antibiotics susceptibility screening for bacterial strains in laboratory environment.In recent years, excessive utilization of antibiotics has led to the emergence of antibiotic microbial resistance on a planetary scale. This recent phenomenon represents a serious threat to public health, as well as an enormous burden for healthcare systems’ budgets worldwide. Novel, rapid and cheap methods for antibiotic susceptibility screening are urgently needed for this obstacle to be overcome. In this paper, we present a microfluidic device for on-chip antibiotic resistance testing, which allows for antibiotic microbial resistance detection within 6 hours. The design, fabrication and experimental utilization of the device are thoroughly described and analyzed, as well as possibilities for future automation of the whole process. The accessibility of such a device for all people, regardless of economic status, was of utmost importance for us during the development of the project.

14.
2021 IEEE Biomedical Circuits and Systems Conference, BioCAS 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1704313

ABSTRACT

Microfluidic biochips are being adopted today in point-of-care diagnostics, e.g., COVID-19 testing;therefore, it is critical to ensure integrity of bio-sample before bioassays are run on-chip. A security technique called molecular barcoding was recently proposed to thwart sample-forgery attacks in DNA forensics. Molecular barcoding refers to addition of unique DNA molecules in bio-samples, and the sequence of the added DNA sample serves as a distinct 'barcode' for the sample. The existence of the added molecule can be validated using polymerase chain reaction (PCR) and gel electrophoresis. However, this security solution has several limitations: (1) the lack of robustness of the barcode molecules when they are added to other genomic DNA (e.g., samples collected for diagnostics);(2) the need for special bulk instrumentation for validation;(3) the need for human intervention during the overall process. To overcome the limitations, we design a set of robust molecular barcodes that can be validated using both traditional polymerase chain reaction and loop mediated isothermal amplification (LAMP). The validation using LAMP can be executed on a small-in-size and portable digital microfluidic biochip (DMFB). Our LAMP workflow includes a color-changing visual indicator for simple, rapid identification of the barcode existence in solutions. We first demonstrate the proposed security workflow using benchtop techniques. Next, we fabricate a printed circuit board (PCB)-based DMFB with heaters and demonstrate, for the first time, the LAMP assay on a DMFB. © 2021 IEEE.

15.
Mathematical Problems in Engineering ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1701014

ABSTRACT

This work presents the splitting dynamics of low-viscous fingers inside the single bifurcating channel through the surface wettability of daughter branches. The propagation of low-viscous fingers inside branching microchannels have importance in many applications, such as microfluidics, biofluid mechanics (pulmonary airway reopening), and biochemical testing. Several numerical simulations are performed where a water finger propagates inside the silicon oil-filled bifurcating channel, and at the bifurcating tip, it splits into two fingers and these fingers propagate into the separate daughter branches. It is noticed that the behaviour of finger splitting at the bifurcating tip depends upon numerous parameters such as surface wettability, capillary number, viscosity ratio, and surface tension. This study aims to trigger the behaviour of finger splitting through the surface wettability of daughter branches θ1,θ2. Therefore, a series of numerical simulations are performed by considering four different surface wettability configurations of daughter branches, i.e., θ1,θ2∈78°,78°;78°,118°;78°,150°;150°,150°. According to the results obtained from numerical simulations, finger splitting may be categorized into three types based on splitting ratio λ, i.e., symmetrical splitting, nonsymmetrical splitting, and reversal (no) splitting. It is noticed that the surface wettability of both daughter branches is either hydrophilic 78°,78° or superhydrophobic 150°,150°, providing symmetrical splitting. The surface wettability of one of the daughter branches is hydrophilic and another is hydrophobic 78°,118°, providing nonsymmetrical splitting. The surface wettability of one of the daughter branches is hydrophilic and another is superhydrophobic 78°,150°, providing reversal splitting. The findings of this investigation may be incorporated in the fields of biochemical testing and occulted pulmonary airways reopening as well as respiratory diseases such as COVID-19.

16.
Micromachines (Basel) ; 13(2)2022 Jan 27.
Article in English | MEDLINE | ID: covidwho-1686889

ABSTRACT

Point-of-care (POC) tests capable of individual health monitoring, transmission reduction, and contact tracing are especially important in a pandemic such as the coronavirus disease 2019 (COVID-19). We develop a disposable POC cartridge that can be mass produced to detect the SARS-CoV-2 N gene through real-time quantitative polymerase chain reaction (qPCR) based on digital microfluidics (DMF). Several critical parameters are studied and improved, including droplet volume consistency, temperature uniformity, and fluorescence intensity linearity on the designed DMF cartridge. The qPCR results showed high accuracy and efficiency for two primer-probe sets of N1 and N2 target regions of the SARS-CoV-2 N gene on the DMF cartridge. Having multiple droplet tracks for qPCR, the presented DMF cartridge can perform multiple tests and controls at once.

17.
Sci China Chem ; : 1-11, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1669939

ABSTRACT

Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to prevent the further spread of the epidemic. An optimized RPA-Cas12a-based platform combined with digital microfluidics (DMF), the RCD platform, was established to achieve the automated, rapid detection of influenza viruses and SARS-CoV-2. The probe in the RPA-Cas12a system was optimized to produce maximal fluorescence to increase the amplification signal. The reaction droplets in the platform were all at the microliter level and the detection could be accomplished within 30 min due to the effective mixing of droplets by digital microfluidic technology. The whole process from amplification to recognition is completed in the chip, which reduces the risk of aerosol contamination. One chip can contain multiple detection reaction areas, offering the potential for customized detection. The RCD platform demonstrated a high level of sensitivity, specificity (no false positives or negatives), speed (≤30 min), automation and multiplexing. We also used the RCD platform to detect nucleic acids from influenza patients and COVID-19 patients. The results were consistent with the findings of qPCR. The RCD platform is a one-step, rapid, highly sensitive and specific method with the advantages of digital microfluidic technology, which circumvents the shortcomings of manual operation. The development of the RCD platform provides potential for the isothermal automatic detection of nucleic acids during epidemics. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11426-021-1169-1.

18.
Chinese Journal of Analytical Chemistry ; 50(1):25-38, 2022.
Article in Chinese | Web of Science | ID: covidwho-1667872

ABSTRACT

Digital polymerase chain reaction (PCR), as a nucleic acid detection technology with wide application prospect, has become one of the most accurate nucleic acid detection technology at present. Multiplex detection is an important direction for the development of digital PCR technique. With the development of microfluidic technology, multiplex digital PCR technique has become more and more mature. This paper reviewed the research progresses of multiplex digital PCR in recent years, especially summarized the implementation of multiplex digital PCR technique in the past five years, and introduced the application of multiplex digital PCR technique in hot areas such as liquid biopsy, transgenic detection, and SARS-Cov-2 detection. Finally, the issues and challenges faced by multiplex digital PCR technique were discussed and the future direction of the technology was foreseen.

19.
Progress in Biochemistry and Biophysics ; 49(1):233-241, 2022.
Article in English | Web of Science | ID: covidwho-1667803

ABSTRACT

Proteins are the executors of various kinds of metabolism and regulation in cells and they are also the most important target molecules of pathogenic factors and drugs. The study of protein expression is necessary to understand life, disease processes and drug effects. At present, routine protein detection methods in clinical practice require the support of large equipment. However, with the development of medical technologies and especially under the special background of the coronavirus (COVID-19) pandemic, point-of-care testing (POCT, also known as on-site testing and bedside testing) has become the current development trend. POCT can improve the ways of interaction between patients and doctors and create a positive approach to medical treatment. In addition to diagnosing and treating diseases, POCT has advantages in both on-site and remote detection for personnel engaged in emergency work. Therefore, it is very important to develop accurate, sensitive, simple and fast protein POCT. To develop miniature devices for POCT, many new approaches have been attempted in recent years, including microfluidics, electrochemical biosensors, smart phones, artificial intelligence, and wearable devices. Microfluidics deals with small quantities of samples and is a universal platform for integrating a variety of technologies, such as immunochemistry, electrochemistry, and mass spectrometry. With microfluidic technology, the sample size, reaction time, and detection limit could be easily improved to satisfactory levels. The use of electrochemistry in detecting proteins has opened a new field in POCT. Since the core of electrochemistry lies in the nanocatalyst development, the rapidly growing research on nanomaterials also has facilitated and expanded the areas of POCT applications. Furthermore, the current frontier technologies employing 5G, artificial intelligence, and wearable devices have not only generated new possibilities but also greatly inspired scientists to create novel POCT devices. In conclusion, with the increasing demand of people and the continuous progress of science and technology, the development direction of future protein detection methods will be focused on portability, intellectualization, rapidity, integration of diagnosis and treatment by multidisciplinary approaches for better application in clinical practice and applicability for bedside and home testing.

20.
Sens Actuators B Chem ; 358: 131447, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1649680

ABSTRACT

An integrated microfluidic platform (IMP) utilizing real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) was developed here for detection and quantification of three genes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; i.e., coronavirus diseases 2019 (COVID-19)): RNA-dependent RNA polymerase, the envelope gene, and the nucleocapsid gene for molecular diagnosis. The IMP comprised a microfluidic chip, a temperature control module, a fluidic control module that collectively carried out viral lysis, RNA extraction, RT-LAMP, and the real-time detection within 90 min in an automatic format. A limit of detection of 5 × 103 copies/reaction for each gene was determined with three samples including synthesized RNAs, inactive viruses, and RNAs extracted from clinical samples; this compact platform could be a useful tool for COVID-19 diagnostics.

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