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...

Biofunctionalization of microchannels is of great concern in the fabrication of microfluidic devices. Different substrates such as glass slides, papers, polymers, and beads require different biofunctionalization approaches granting the utilization of microfluidics in several biomedical applications. Covalent immobilization of biomolecules inside the microchannels is achieved by chemical modification of the surface such as silanization or introducing different coupling agents. Although creating biointerfaces that are covalently bonded to the microchannel surface necessitates multiple steps of surface modification and incubation times, it bestows a robust biointerface capable of withstanding high shear stresses and harsh conditions without dissipating the biofunctionality. Regarding the applications that do not require robustness and long‐term stability, noncovalent attachment of biomolecules such as van der Waals and hydrophobic interactions are adequate to successfully create a functional biointerface. This review summarizes the various biofunctionalization approaches used in the most common microfluidic substrates: glass and paper. In addition, several biofunctionalization examples are proposed and described in detail along with their associated applications.

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