Antibody Micropatterned Lubricant‐Infused Biosensors Enable Sub‐Picogram Immunofluorescence Detection of Interleukin 6 in Human Whole Plasma

Abstract

Recent studies have shown a correlation between elevated interleukin 6 (IL-6) concentrations and the risk of respiratory failure in COVID-19 patients. Therefore, detection of IL-6 at low concentrations permits early diagnosis of worstcase outcome in viral respiratory infections. Here, a versatile biointerface is presented that eliminates nonspecific adhesion and thus enables immunofluorescence detection of IL-6 in whole human plasma or whole human blood during coagulation, down to a limit of detection of 0.5 pg mL −1. The sensitivity of the developed lubricant-infused biosensor for immunofluorescence assays in detecting low molecular weight proteins such as IL-6 is facilitated by i) producing a bioink in which the capture antibody is functionalized by an epoxy-based silane for covalent linkage to the fluorosilanized surface and ii) suppressing nonspecific adhesion by patterning the developed bioink into a lubricant-infused coating. The developed biosensor addresses one of the major challenges for biosensing in complex fluids, namely nonspecific adhesion, therefore paving the way for highly sensitive biosensing in complex fluids. where significantly elevated levels indicate aggressive tumor growth or viral load and poor prognosis in patients. [2,10] Additionally, IL-6 is an important anti-inflammatory cytokine that induces acute responses in chronic inflammatory pathologies. As such, there has been an increasing interest in the use of IL-6 as a biomarker for the diagnosis of early stages of viral infections, cancer, and chronic inflammation. [9-11] A practical IL-6 biosensor should provide a low limit of detection (LOD) (≤5 pg mL −1) and acceptable linear dynamic range (1-100 pg mL −1) in complex fluids, in addition to accuracy, facile operation, and amenable to mass production. [11,12] There are a large number of different IL-6 detection techniques that have been reported in the literature including electrochemical sensors, [13-22] surface plasmon resonance (SPR), [23-25] chemiluminescence immunoassay (CLIA), [26-29] and immunofluorescence assays (IFA), [30-33] Utilizing 0-and 1-D materials such as carbon nanotubes (CNTs), [14,16] nanoparticles and nanowires, [13,19] as well as porous nanoparticles, [15] optical fibers, [32] and microfluidic platforms, [28] have enabled higher sensitivity in IL-6 detection and to date, electrochemical methods have proven to be the most promising candidate for detection of IL-6 at very low concentrations (0.33 pg mL −1 in buffer) with a wide linear dynamic range. [22] While reported IL-6 biosensors have demonstrated satisfactory LODs in buffer or processed serum, their performance in human whole plasma declines significantly, leading to higher LOD's and/or false positive results. In electrochemical sensors, for example, the nonspecific attachment of biological entities in plasma or blood can interfere with the resistivity at the electrodes thereby deteriorating their sensitivity for detection of IL-6 at clinically relevant concentrations. [34] So far, the lowest theoretical LOD fo...

An Intelligent Graphene‐Based Biosensing Device for Cytokine Storm Syndrome Biomarkers Detection in Human Biofluids

“…[ 4 ] Currently, CSS is identified as a poor prognosis for critical COVID‐19 cases and abnormal elevations in cytokines levels could be used for indicating the progression to severe or critical COVID‐19. [ 5–7 ] This consensus is already verified by the clinical data obtained from 41 COVID‐19 patients in Jin Yin‐tan Hospital, Wuhan, China, at the early beginning of 2020. [ 8 ] Hence, it is of great significance to develop devices for monitoring cytokines levels in COVID‐19 patients, thereby enabling detecting COVID‐19 patients that are worsening and to treat them before they become critically ill.…”

Transparent and Highly Flexible Hierarchically Structured Polydimethylsiloxane Surfaces Suppress Bacterial Attachment and Thrombosis Under Static and Dynamic Conditions

“…To this end, surface texturing has been identified as a means through which a lubricant layer can achieve greater stability and retention under flow. [26,27] When microtextured surfaces are infused with lubricant, the structures that constitute its surface mediate the spreading of the lubricant across the surface through capillary wicking. [28] Combined with intermolecular interactions between a treated surface and a matching lubricant, these capillary forces hold the lubricant layer in place.…”

“…[ 25 ] Although promising, these lubricant layers suffer from low stability under dynamic fluid flow, as would be experienced within various biomedical devices, resulting in a loss of repellency over time. [ 26 ] To effectively use lubricant‐infused surfaces for widespread antibiofouling purposes, increased lubricant retention is imperative. To this end, surface texturing has been identified as a means through which a lubricant layer can achieve greater stability and retention under flow.…”

“…Yet, when exposed to vigorous fluid flow, the shear stress experienced by the surface can act against capillary forces that help immobilize the lubricant layer, leading to its deterioration. [ 26 ] Introducing hierarchy to microstructures through nanoscale modifications overcomes this barrier, since the presence of nanoscale entities substantially increases capillary forces. [ 26 ] Accordingly, a lubricant‐infused hierarchical surface would be expected to exhibit excellent biological repellency and strong lubricant retention.…”

Bioinspired Repellent Pipette Tips with Low Retention Properties Prevent Contamination in Handling Biological Samples

“…To address this issue, the surface of the tip must be modi ed such that it exhibits low a nity to low surface tension liquids. Such surfaces, referred to as omniphobic, are characterized by their ability to repel all liquids despite their cohesive force strengths 17,18 . A static contact angle of 90° or higher accompanied by a low dynamic angle hysteresis and a low sliding angle of 5° or less are generally characteristic of omniphobic surfaces 19,20 .…”