Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis

Abstract

Sepsis is an often fatal condition that arises when the immune response to an infection causes widespread systemic organ injury. A critical unmet need in combating sepsis is the lack of accurate early biomarkers that produce actionable results in busy clinical settings. Here, we report the development of a point-of-care platform for rapid sepsis detection. Termed IBS (integrated biosensor for sepsis), our approach leverages i) the newly-found pathophysiological role of cytokine interleukin-3 (IL-3) in early sepsis, and ii) a hybrid magneto-electrochemical sensor for IL-3 detection. The developed platform produces test results within 1 hour from native blood samples, and detects IL-3 at a sensitivity of <10 pg/mL; this performance is >5-times faster and >10-times more sensitive than a current gold standard, enzyme-linked immunoadsorbent assay. Using clinical samples, we show that high plasma IL-3 levels are associated with high organ failure rate and thus greater risk of mortality, confirming the potential of IL-3 as an early diagnostic biomarker. Compact and fast, the IBS platform can be readily integrated into clinical workflows, enabling timely diagnosis and proactive treatment of sepsis.

The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity

“…In this cohort, there was no significant difference in circulating IL-3 protein abundance at day 0 versus day 1 or day 2 following sepsis diagnosis (2). However, in a separate cohort, IL-3 was significantly elevated in patients with sepsis relative to healthy controls (29). We sought to determine whether circulating IL-3 differed in a more homogenous population at risk for ARDS because a subset of patients at risk for or with ARDS have excessive inflammation and cytokine storm in the lung (30,31).…”

Biomarkers for Point-of-Care Diagnosis of Sepsis

“…Recent work has led to the development of a microelectrode sensor for the measurement of IL-6 with an assay time of around 2.5 min [125]. Work on more novel biomarkers has also been done by Min and co-workers [126], who developed a biosensor for the measurement of IL-3 and have attempted to validate its use in a small cohort of septic and control patients. In addition to biosensors, increasing the sensitivity of more widely used absorption spectrophotometric measurements has been achieved through the use of techniques such as cavity-enhanced absorption spectrometry (CEAS) [127].…”

A perspective on sepsis pathogenesis, biomarkers and diagnosis: A concise survey

“…Min et al. (2018) reported the development of a POC platform, termed IBS (integrated biosensor for sepsis) for rapid and reliable sepsis identification. A portable platform comprising of a disposable kit (to capture sepsis biomarker interleukin‐3 (IL‐3) on magnetic beads and label it for subsequent electrochemical measurements), an electrical detection system (to measure electrical current for IL‐3 quantification), a microcontroller unit for signal processing and a bluetooth module for wireless communication, all packaged into a single monolithic device, outperformed the conventional enzyme‐linked immunosorbent assays (ELISA) by providing > 5 times faster response, >10 times more sensitivity and an order of magnitude larger dynamic detection range.…”