# Label-Free Electrochemical Interleukin‑6 Sensor Exploiting rGO-Ti3C2T x  MXene Nanocomposites

**Authors:** Rohit Gupta, Ashish Kalkal, Priya Mandal, Diptiranjan Paital, David Brealey, Manish K. Tiwari

PMC · DOI: 10.1021/acsami.5c06701 · ACS Applied Materials & Interfaces · 2025-07-24

## TL;DR

This paper presents a new electrochemical sensor for detecting IL-6, a key inflammation marker, using nanomaterials and advanced modeling for fast and accurate results.

## Contribution

A novel label-free IL-6 sensor using rGO-Ti3C2Tx MXene nanocomposites and a genetic algorithm-based model for optimized performance.

## Key findings

- The sensor achieves a detection limit of single-digit pg/mL with a range of 3–1000 pg/mL.
- It offers a sample-to-answer time of ~15 minutes, 12 times faster than traditional ELISA.
- The sensor shows high selectivity and stability for a month.

## Abstract

This work introduces
a novel, rapid, label-free, affinity-enabled
electrochemical sensor for the detection of interleukin-6 (IL-6),
a critical proinflammatory cytokine associated with severe conditions
like sepsis and COVID-19. Unlike conventional approaches, this platform
leverages an innovative biofunctional nanocomposite of Ti3C2T
x
 MXene, tetraethylene
pentaamine-functionalized reduced graphene oxide (TEPA-rGO), and Nafion,
functionalized with anti-IL-6 antibodies, integrated into a carbon-based
screen-printed three-electrode chip. The system achieves unprecedented
sensitivity in IL-6 quantification, with a single-digit pg/mL detection
limit and a broad range of 3–1000 pg/mL using ∼5 μL
of serum. The sensor design is uniquely enhanced through the introduction
of a genetic algorithm-based thin-layer diffusion model, which optimizes
critical, previously unknown electrochemical transport parameters,
including diffusion coefficient, rate constant, charge transfer coefficient,
and electrochemically active surface area. This approach represents
a significant advancement in biosensor modeling and performance tuning.
The sensor demonstrates exceptional selectivity (signal-to-noise ratio
∼ 6.9) against relevant interferents (e.g., sepsis-related
antigens, small molecules, electroactive compounds), retains operational
stability for a month, and offers a sample-to-answer time of ∼15
min (i.e., up to 12 times faster than traditional ELISA), while maintaining
comparable sensitivity. Detailed morphological, topographical, and
chemical analyses validate the structural and functional integrity
of the TEPA-rGO/MXene/Nafion nanocomposite. By combining cutting-edge
nanomaterials with advanced computational modeling, this IL-6 sensor
sets a new benchmark for rapid, precise cytokine detection, offering
transformative potential for early disease diagnosis and prognosis.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Chemicals:** tetraethylene pentaamine (PubChem CID 8197)
- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** sepsis (MESH:D018805), COVID-19 (MESH:D000086382)
- **Chemicals:** Ti3C2Tx MXene (-), TEPA (MESH:D013721), Nafion (MESH:C040402), MXene (MESH:C000723374), carbon (MESH:D002244)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12332829/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12332829/full.md

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Source: https://tomesphere.com/paper/PMC12332829