Towards an Integrated System as Point-of-Care Device for the Optical Detection of Sepsis Biomarkers

Abstract

Severe infection and sepsis are a common, expensive, and frequently fatal conditions in critically ill patients. The sepsis diagnosis is not trivial, since it is an extremely complex chain of events involving inflammatory and anti-inflammatory processes, cellular reactions, and circulatory disorders. For these reasons, delay in diagnosis and initiation of drug treatments have shown to be crucial for this pathology. Moreover, a multitude of biomarkers has been proposed, many more than for other pathologies. In order to select optimal treatments for the highly heterogeneous group of sepsis patients and to reduce costs, novel multiplexed tools that better characterize the patient and his or her specific immune response are highly desired. In order to achieve the fundament of drastically improved multi-analyte detection and to attain low limits of detection in diagnostics, the area of point-of-care testing (POCT) technology is developing quickly, leading to the production of instruments, the reliability of which is continuously increasing. For this purpose, a selection of two biomarkers—C-reactive protein (CRP) and neopterin (NP)—was studied in this paper and a fluorescence-based integrated optical system, suitable for future POCT applications, was implemented that is capable of performing the simultaneous measurement of the two different biomarkers in replicate. A limit of detection of 10 and 2.1 µg L−1 was achieved for CRP and NP spiked in commercially available human serum, respectively. Moreover, measurements on both biomarkers were also performed on serum samples collected from septic patients.

Long period grating in double cladding fiber coated with graphene oxide as high-performance optical platform for biosensing

“…The surface passivation was obtained with 1% (w/v) of BSA in PBS, treating the surface for 20 min and then washing for 10 min in PBS. The passivation step is useful in order to block the remaining activated carboxylic groups, so as to prevent non-specific adsorption onto the surface ( Berneschi et al, 2017 ; Giannetti et al, 2020 ; Lichtenberg et al, 2019 ; Pisco and Cusano, 2020 ; Vaiano et al, 2016 ; Zubiate et al, 2019 ).…”

Microfluidic systems for infectious disease diagnostics

“…A LOD of 10 ng mL −1 for CRP and 2.1 ng mL −1 for NP (spiked in human serum) was achieved, respectively, with a total assay time of 20 min. 388 Molinero-Fernández et al combined a PCT magneto-immunoassay format with flow-based electrochemical on-chip detection. The immunocomplex was injected in a cross-channel microfluidic chip and retained in the main channel while an enzymatic substrate was electrokinetically driven over the magnetic bead plug for downstream in-channel amperometric detection (LOD of 0.04 ng mL −1 for PCT standard solutions, analysis time <20 min).…”

Fiber optic biosensor for inflammatory markers based on long period grating

“…The unattached antibodies were removed by washing in phosphate-buffered saline (PBS, 40 mM at pH 7.4) for 10 minutes at a faster flow rate of 150 µL/min. The surface passivation was obtained with 1% (w/v) of bovine serum albumin (BSA) in PBS, by treating the surface for 20 minutes and then washing for 10 minutes in PBS buffer to remove the BSA excess The passivation step blocked the remaining activated carboxylic groups, so as to prevent non-specific adsorption onto the surface [21], [22]. function of time, is reported in Fig.…”