Point‐of‐critical‐care diagnostics for sepsis enabled by multiplexed micro and nanosensing technologies

Abstract

Sepsis is responsible for the highest economic and mortality burden in critical care settings around the world, prompting the World Health Organization in 2018 to designate it as a global health priority. Despite its high universal prevalence and mortality rate, a disproportionately low amount of sponsored research funding is directed toward diagnosis and treatment of sepsis, when early treatment has been shown to significantly improve survival. Additionally, current technologies and methods are inadequate to provide an accurate and timely diagnosis of septic patients in multiple clinical environments. For improved patient outcomes, a comprehensive immunological evaluation is critical which is comprised of both traditional testing and quantifying recently proposed biomarkers for sepsis. There is an urgent need to develop novel point‐of‐care, low‐cost systems which can accurately stratify patients. These point‐of‐critical‐care sensors should adopt a multiplexed approach utilizing multimodal sensing for heterogenous biomarker detection. For effective multiplexing, the sensors must satisfy criteria including rapid sample to result delivery, low sample volumes for clinical sample sparring, and reduced costs per test. A compendium of currently developed multiplexed micro and nano (M/N)‐based diagnostic technologies for potential applications toward sepsis are presented. We have also explored the various biomarkers targeted for sepsis including immune cell morphology changes, circulating proteins, small molecules, and presence of infectious pathogens. An overview of different M/N detection mechanisms are also provided, along with recent advances in related nanotechnologies which have shown improved patient outcomes and perspectives on what future successful technologies may encompass. This article is categorized under: Diagnostic Tools > Biosensing

Rapid Detection of Sepsis: Recent Advances in Biomarker Sensing Platforms

“…23 However, there exist many examples of FDA-approved and commercially available sepsis sensors that focus on the detection of pathogens through PCRbased methodologies. 24 As a result, many of these platforms operate on a time scale of several hours and require PCR or additional complex instrumentation, reducing their usefulness as a rapid POC tool.…”

“…Currently, most reported devices are optimized for a single analyte and may not provide sufficient diagnostic power. 24 Despite the promising diagnostic and prognostic roles of biomarkers, no single marker is ideal or specific. Thus, an assay that could detect multiple key biomarkers and monitor their levels rapidly is critically important.…”

“…Specifically, rigorous validation of the biomarker assaysincluding its precision, limit of detection, limit of quantification, linearity, specificity, and stabilitymust be demonstrated and quantified . However, there exist many examples of FDA-approved and commercially available sepsis sensors that focus on the detection of pathogens through PCR-based methodologies . As a result, many of these platforms operate on a time scale of several hours and require PCR or additional complex instrumentation, reducing their usefulness as a rapid POC tool.…”

Time‐domain signal averaging to improve microparticles detection and enumeration accuracy in a microfluidic impedance cytometer

“…While even higher sampling rates may facilitate other signal averaging methods that subdivides the data, they come at the cost of exceedingly large original file sizes (~100 of MBs) after only a few seconds of recording. This is unsatisfactory notably for common microfluidic impedance counting purposes such as point‐of‐care diagnostics (Ashley & Hassan, 2021). From using SMA in this report, processing time was increased on the order of minutes, totaling less than 10 min from sample collection to applying digital filters, SMA, and analyzing particle metrics.…”

“…While numerous configurations have been researched and implemented, typically this consists of bonded electrodes to generate an electric field on the surface of microchannels that facilitate microfluidic flow. EIS has many advantages over other micro‐scale detection options, including a diversity of materials which can be measured (e.g., proteins, Baraket et al, 2017; Mok et al, 2014; Panneer Selvam & Prasad, 2017; immune cells, Hassan et al, 2017; Watkins et al, 2013; pathogens, Lam et al, 2013; particulate matter, Carminati et al, 2014; Ciccarella et al, 2016; and more, Guo et al, 2015; Shi et al, 2021; Teass et al, 1998; Zhang et al, 2021), label‐free detection capabilities, requiring small sample volumes, relatively inexpensive fabrication options, and the multiplexing ability to quantify many different materials altogether (Ashley & Hassan, 2021; Prakash et al, 2020). Additionally, at low voltages, the detection process is non‐destructive to sample analytes, and many EIS systems can be performed without manual sample pre‐processing (Baraket et al, 2017; Hassan et al, 2017).…”