Integration of sample preparation and analysis into an optofluidic chip for multi-target disease detection

Abstract

Detection of molecular biomarkers with high specificity and sensitivity from biological samples requires both sophisticated sample preparation and subsequent analysis. These tasks are often carried out on separate platforms which increases required sample volumes and the risk of errors, sample loss, and contamination. Here, we present an optofluidic platform which combines an optical detection section with single nucleic acid strand sensitivity, and a sample processing unit capable of on-chip, specific extraction and labeling of nucleic acid and protein targets in complex biological matrices. First, on-chip labeling and detection of individual lambda DNA molecule down to concentrations of 8fM is demonstrated. Subsequently, we demonstrate the simultaneous capture, fluorescence tagging and detection of both Zika specific nucleic acid and NS-1 protein targets in both buffer and human serum. We show that the dual DNA and protein assay allows for successful differentiation and diagnosis of Zika against cross-reacting species like dengue.

Optofluidic multiplex detection of single SARS-CoV-2 and influenza A antigens using a novel bright fluorescent probe assay

“…This will require commercial product development that leverages the economies of scale of silicon microchip fabrication and photonic component suppliers. In addition, this process can be further advanced by chip-level integration of additional assay elements that have recently been demonstrated, including LoC sample processing (40) and light sources (41).…”

Optical trapping assisted label-free and amplification-free detection of SARS-CoV-2 RNAs with an optofluidic nanopore sensor

“…Furthermore, the TACRE assay can be functionally expanded, e.g. by applying the assay to protein targets ( Meena et al, 2018 ), by implementing the sample preparation step on a chip ( Meena et al, 2018 ), implementing multi-channel, multiplex detection, or by applying advanced signal processing for real-time analysis of the nanopore signals. As a result, this integrated nanopore sensor has the potential to be used as a simple, ultrasensitive, and rapid molecular analysis tool with a diverse range of applications in disease diagnostics and biomedicine.…”

“…Bead-based SPE is ideally suited for the TACRE assay as targets are selectively bound to the very microbeads that act as carriers to deliver them to the nanopore, and because SPE can be applied to different molecular target types, including nucleic acids, proteins, etc. ( Meena et al, 2018 ). Fig.…”

On‐Chip Optical Detection of Viruses: A Review

“…In other works, optofluidic systems with MMI multiplexing were used to detect Zika nucleic acid and protein biomarkers. [ 57,105,129,130 ] Figure 8d shows a solid‐phase extraction method using beads. Streptavidin‐coated magnetic microspheres bound with biotin‐functionalized Zika virus monoclonal antibody or biotinylated complimentary oligonucleotide formed the pulldown complex.…”