A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy

Abstract

The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.

Amplification-Free SARS-CoV-2 Detection Using Nanoyeast-scFv and Ultrasensitive Plasmonic Nanobox-Integrated Nanomixing Microassay

“… 8 , 41 , 42 The achieved limit of detection met the clinical requirement for screening COVID-19 patients (∼100 virus/μL). 43 Such a low limit of detection on the nanoyest-scFv-integrated SERS microarray platform can be attributed to the following three key features: the high affinity contributed from the engineered S309 nanoyeast-scFvs; the nanomixing enhanced molecular interactions on the microelectrodes; and the superbright SERS nanotags 31 binding to multiple RBD on the viral surfaces.…”

Human metabolite detection by surface-enhanced Raman spectroscopy

“…This can be fulfilled through forming particle aggregations, enlarging the surface area, and fabricating plasmon-coupling structures [ [124] , [125] , [126] ]. For example, colloidal aggregates are preferred in liquid phase, and nanopillar patterns [ 127 ], film layers [ 100 ] as well as porous structures [ 100 ] are frequently reported on a planar substrate. By dripping colloids on a substrate, the random agglomerates in “coffee ring” can be formed [ 116 ].…”

Toward precision oncology: SERS microfluidic systems for multiplex biomarker analysis in liquid biopsy

“…4c, Li and colleagues developed a digital nanopillar platform integrated with SERS barcode detection system for multiplex quantification of single cytokine molecule (i.e., FGF-2, G-CSF, GM-CSF, CX3CL1) to track immune toxicities in melanoma patients receiving immune checkpoint blockade therapy. 43 Single cytokine molecule counting of four targets on nanopillar platform was based on three key concepts: (i) Rayleigh criterion separation for fabricating discrete single cytokine nanopillar chip with discretely separated compartments; (ii) probability-driven Poisson distribution for control of target concentration; and (iii) single particle active SERS nanotags for confocal SERS mapping. The gold topped nanopillars were functionalized with target specific capture antibodies for single cytokine capture and SERS nanotags were used for target recognition via SERS spectroscopy.…”