# Cellulose-Based Colorimetric Test Strips for SARS-CoV-2 Antibody Detection

**Authors:** Mariana P. Sousa, Ana Cláudia Pereira, Bárbara Correia, Anália do Carmo, Ana Miguel Matos, Maria Teresa Cruz, Felismina T. C. Moreira

PMC · DOI: 10.3390/bios15060390 · 2025-06-17

## TL;DR

This paper introduces low-cost, paper-based tests that detect SARS-CoV-2 antibodies using a new color-changing method, offering a simple and effective tool for monitoring immune responses.

## Contribution

The first use of glutaraldehyde as a protein dye in paper-based biosensors for antibody detection.

## Key findings

- Both sensors showed a linear correlation between antibody concentration and RGB values in buffer and serum.
- The VLP sensor detected antibodies in the range of 1.0–20 µg/mL in diluted serum.
- The N-protein sensor detected antibodies in the range of 1.0–40 µg/mL in diluted serum.

## Abstract

The COVID-19 pandemic highlighted the need for rapid, cost-effective tools to monitor transmission and immune response. We developed two novel paper-based colorimetric biosensors using glutaraldehyde as a protein dye—its first use in this context. Glutaraldehyde reacts with amino groups to generate a brown color, enabling detection of SARS-CoV-2 antibodies. Wathman filter paper was functionalized with (3-aminopropyl)triethoxysilane (APTES) to immobilize virus-like particles (VLPs) and nucleocapsid protein (N-protein) as biorecognition elements. Upon incubation with antibody-containing samples, glutaraldehyde enabled colorimetric detection using RGB analysis in ImageJ software. Both sensors showed a linear correlation between antibody concentration and RGB values in buffer and serum. The VLP sensor responded linearly within the range of 1.0–20 µg/mL (green coordinate) in 500-fold diluted serum and the N-protein sensor from 1.0–40 µg/mL (blue coordinate) in 250-fold diluted serum. Both sensors demonstrated good selectivity, with glucose causing up to 18% interference. These biosensors represent a paradigm shift, as they provide a sensitive, user-friendly, and cost-effective option for semi-quantitative serological analysis. Furthermore, their versatility goes beyond the detection of SARS-CoV-2 antibodies and suggests broader applicability for various molecular targets.

## Linked entities

- **Proteins:** nucleocapsid protein (nucleocapsid protein)
- **Chemicals:** glutaraldehyde (PubChem CID 3485), (3-aminopropyl)triethoxysilane (PubChem CID 13521), glucose (PubChem CID 5793)
- **Diseases:** SARS-CoV-2 (MONDO:0100096), COVID-19 (MONDO:0100096)

## Full-text entities

- **Diseases:** COVID-19 (MESH:D000086382)
- **Chemicals:** (3-aminopropyl)triethoxysilane (MESH:C477625), glucose (MESH:D005947), Cellulose (MESH:D002482), Glutaraldehyde (MESH:D005976)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12190371/full.md

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Source: https://tomesphere.com/paper/PMC12190371