# Optimizing Surface Functionalization for Aptameric Graphene Nanosensors in Undiluted Physiological Media

## TL;DR

This paper improves graphene nanosensors for detecting biomarkers in undiluted blood by optimizing surface coatings, achieving much higher sensitivity.

## Contribution

A systematic optimization of PEG and aptamer surface functionalization for graphene nanosensors in undiluted physiological media.

## Key findings

- Serial modification with 5000 Da PEG and a 94 nt DNA aptamer improved CRP detection in undiluted serum.
- The optimized design achieved a limit of detection (LOD) of 27 pM for CRP, a 1000-fold improvement over prior methods.
- The sensor effectively reduced nonspecific binding while maintaining strong responsivity to target biomarkers.

## Abstract

This paper presents the optimization of surface modification for aptameric graphene nanosensors for the measurement of biomarkers in undiluted physiological media. In these sensors, graphene transduces the binding between an aptamer and the intended target biomarker into a measurable signal while being coated with a polyethylene glycol (PEG) nanolayer to minimize nonspecific adsorption of matrix molecules. We perform a systematic study of the aptamer and PEG attachment schemes and parameters, including the impact of the serial or parallel PEG–aptamer attachment scheme, PEG molecular weight and surface density, and aptamer surface density on the sensor behavior, such as the responsivity to biomarker concentration changes, and importantly, they are used for operation in physiological media and have the ability to reject nonspecific binding to interfering molecules. We then use the understanding from this parametric study to identify graphene nanosensor designs that are optimally functionalized with PEG and aptamers to be strongly responsive to target biomarkers and effectively reduce nonspecific adsorption of interferents, thereby enabling sensitive and specific biomarker measurements in undiluted physiological media. The experimental results show that nanosensors that were optimized via serial modification with 5000 Da PEG at 15 mM and a 94 nt DNA aptamer at 500 nM allowed specific measurement of C-reactive protein (CRP) in undiluted human serum with a limit of detection (LOD) down to 27 pM, representing an up to 1000-fold improvement compared to previously reported CRP measurements.