Abstract

The rapid detection and quantification of infectious pathogens is an essential component to the control of potentially lethal outbreaks among human populations worldwide. Several of these highly infectious pathogens, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been cemented in human history as causing epidemics or pandemics due to their lethality and contagiousness. SARS-CoV-2 is an example of these highly infectious pathogens that have recently become one of the leading causes of globally reported deaths, creating one of the worst economic downturns and health crises in the last century. As a result, the necessity for highly accurate and increasingly rapid on-site diagnostic platforms for highly infectious pathogens, such as SARS-CoV-2, has grown dramatically over the last two years. Current conventional non-microfluidic diagnostic techniques have limitations in their effectiveness as on-site devices due to their large turnaround times, operational costs and the need for laboratory equipment. In this review, we first present criteria, both novel and previously determined, as a foundation for the development of effective and viable on-site microfluidic diagnostic platforms for several notable pathogens, including SARS-CoV-2. This list of criteria includes standards that were set out by the WHO, as well as our own “seven pillars” for effective microfluidic integration. We then evaluate the use of microfluidic integration to improve upon currently, and previously, existing platforms for the detection of infectious pathogens. Finally, we discuss a stage-wise means to translate our findings into a fundamental framework towards the development of more effective on-site SARS-CoV-2 microfluidic-integrated platforms that may facilitate future pandemic diagnostic and research endeavors. Through microfluidic integration, many limitations in currently existing infectious pathogen diagnostic platforms can be eliminated or improved upon.

Highlights

  • We focus on the classification of microfluidic devices, the necessary properties of a microfluidic device that define an integrated microfluidic device, examples of partial and fully integrated microfluidic devices for the detection of infectious pathogens and examples of SARS-CoV-2 diagnostic technology with the potential for clinical on-site translation

  • Many of the conventional detection methods, such as immunoassay and RT-Polymerase chain reaction (PCR), have comparable specificity, sensitivity and short turnaround time as a result of microfluidic integration, it does not compare well to other more novel methods. Detection methods such as microflow cytometry and nanoparticle-based detection may offer more of an inherent advantage to SARS-CoV-2 diagnosis solely based on factors such as detection limit, sample volume and quantitative capabilities; as previously mentioned, an optimal on-site integrated microfluidic diagnostic device for SARS-CoV-2 detection must adhere to the ASSURED standards set out by the World Health Organization (WHO) and the seven pillars of microfluidic integration to the best of their ability [39]

  • We discussed the fundamentals of conventional diagnostic testing platforms, currently existing platforms and the potential applications of integrating microfluidics toward achieving reliable and accessible on-site diagnostic testing devices

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Summary

Introduction

They work under the same mechanism, where the antibody–antigen binding causes a color change to occur, allowing for the quantification of biomarkers [13,14] These immunohistochemistry assays take longer than 24 h to be processed in a laboratory setting and were shown to be quite reliable tools for diagnosing SARS-CoV-2 in patients [15]. Despite the advantages and reliability of the commonly used diagnostic tools, such as PCR and immunohistochemistry assays, there are several shortfalls when it comes to rapid and cost-effective medical diagnosis in the field [16,17,18] These shortfalls become more pronounced and significant when a high demand for accurate and sensitive rapid testing is not being met due to the high cost and infrastructure barriers. SARS-CoV-2, can increase the viability and effectiveness of their diagnostic platforms for on-site use through microfluidic integration

Classification of IMPs
Current Research Trends Guiding the Development of IMPs
WHO On-Site Diagnostic Device Standards
Pillars for Assessing Effective On-Site Diagnostic Tools
Advantages to Microfluidic Integration
On-Device Sample Preparation
Increased Automation
Cost Reduction
Limitations
Shortened Turnaround Time
Maintaining the Level of Accuracy Seen in Conventional Counterparts
Integrating High-Throughput Assays
Using IMPs in the On-Site Detection of Infectious Pathogens
Partially Integrated IMPs in the On-Site Detection of Infectious Pathogens
Fully Integrated IMPs Developed for the Detection of Infectious Pathogens
Findings
Conclusions
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