Quadruple analyte responsive platform: Point-of-care testing and multi-coding logic computation based on metal ions recognition and selective response

Highlights

• The scanner-aided metal ions-responsive system is performed on a portable PAD.

• This S dots-based POCT platform can selectively recognize four metal ions.

• The on-site sensor is suitable for environmental testing in low-resource settings.

• A smart strategy for multi-logic gates is engineered based on this sensing system.

Abstract

While it is recognized that instrumentation techniques can provide precise and sensitive solutions to heavy metal ion monitoring, it remains challenging to transform laboratory testing into a convenient, on-site, and quantitative sensing platform for point-of-care testing (POCT) in a resource-constrained setting. To address these limitations, an affordable and user-friendly colorimetric POCT sensing system is proposed here for selectively monitoring four metal ions (Fe³⁺, Co²⁺, Pb²⁺, and Cd²⁺) based on the sulfur quantum dots (S dots). Quadruple distinct visual signals (green, brown, precipitation, and bright yellow) are presented on the fabricated paper-based analytical devices (PADs) when mixing S dots and metal ions. The high-quality photographs of the PADs are captured by a scanner, while a smartphone App converts visual signals to HSV values. The quantitative analysis relies on the digital colorimetric reading, and the limits of detection are 0.59, 0.47, 0.82, and 0.53 μM for Fe³⁺, Co²⁺, Cd²⁺, and Pb²⁺, respectively. This metal ions-responsive platform is engineered as a smart strategy for multiple logic operations (YES, NOT, AND, INHIBIT, and NOR) by integrating multi-responsive blocks into the S dots with encoded patterns, which improves the computing capability. Accordingly, this strategy demonstrates its potential for on-site environmental testing and sophisticated molecular computation.

Introduction

For numerous biological activities, metal ions are necessary, as well as their regulation is required for the maintenance of proper functioning. However, once metal ions are present in high concentrations or coexist with other toxic metal ions in the environment, the beneficial properties are often counterbalanced by their poisonous effects, and even pose a danger to both the environment and human health. To control their proliferation in water and soil resources and protect human health, methods that can rapidly and accurately monitor the metal ions contamination in the ecological environment are needed. Toward this goal, several attempts such as inductively coupled plasma-mass spectrometry (ICP-MS) (Shih et al., 2016), atomic emission spectrometry (AES) (Kitazume et al., 1999), atomic absorption spectrometry (AAS) (Ezoddin et al., 2010), and stripping voltammetry (SV) (Zhu et al., 2014) have been developed in state-of-the-art laboratories. Meanwhile, some nanomaterials with quantum-size effects, such as noble-metal quantum dots (Nemati and Zare-Dorabei, 2019), carbon nanoparticles (Song et al., 2018), and graphene quantum dots (Xia et al., 2020), make the fluorometric technique play a pivotal role in metal ion detection. Despite the advances in sensitivity and accuracy of such instrumentation techniques, they are restricted by the requirements for expensive instruments, complicated sample preparation, and trained laboratory professionals. As a result, developing an on-site quantitative testing platform that is affordable and portable is highly desirable.

In the last decade, the emerging point-of-care testing (POCT) platforms are more inclined to on-site, visual, and real-time detection rather than the aiding of analytical equipment, making it indispensable in food safety inspection (Hu et al., 2021, Kumar et al., 2019), environmental monitoring (Sivakumar and Lee, 2021), and clinical diagnosis (Bhattacharjee et al., 2017, Xiong et al., 2020). Particularly, paper-based analytical devices (PADs) are an optimal choice for the POCT platform because of the following features of paper: (1) Paper is cheap, easy to handle and store (Qi et al., 2018); (2) The cellulose or cellulose-based polymer hydrophilic channels facilitate solution infiltration into the porous cellulose fibers (Wang et al., 2022). With the aid of a smartphone that possesses the bionic electronic eye-driven signal reader, it quantifies targets by converting the visually discernible color changes into color intensities. For example, Hou and co-workers described the color change generated by the reaction between nitrite and Griess reagent with RGB values, realizing the quantitative detection of nitrite in food samples by a colorimetric PAD (Hou et al., 2020). It is precisely indicated that PAD is a promising candidate for such a POCT platform with the advantages of small size, simplicity of operation, little reagent consumption, and good flexibility. However, another major issue is the light condition, since it affects the photography process and quality, resulting in reading mistakes and incorrect results. Efforts such as rescaling the RGB values (Jalal et al., 2017) and adding optical attachments (Kong et al., 2019) address this issue to a certain extent, but the practical applications of these output devices are still severely constrained by the differences among various smartphone models. In contrast, the flatbed scanner based on a charge-coupled-device (CCD) exhibits ideal imaging and repeatability functions because of the confined scanning space and steady light source (Hou et al., 2021, Medeiros and Lima, 2014). It is worth mentioning that Hou et al. employed a portable scanner with Wi-Fi transmission capability to obtain high-quality images of the PADs. Then they transmitted these pictures to the smartphone through wireless communication to obtain calibration curves of target concentrations (uric acid, glucose, and triglyceride) and RGB values, enabling biomarkers of cardiovascular diseases to be detected (Hou et al., 2021). Accordingly, taking advantage of a user-friendly interface and built-in high-performance sensing module, smartphones can not only simplify quantitative POCT system design, but also enable easy-to-use detection and are easily accessible to the public. Meanwhile, the usage of a scanner guarantees accuracy and sensitivity. Therefore, the POCT platform can break through the limitations of expensive instruments and high-trained laboratory professionals to enable on-site and real-time monitoring.

In portable optical sensing, such sensors commonly used noble metals such as Pt, Pd, Ag, and Au (Ju and Kim, 2015, Sun et al., 2020, Zhang et al., 2018, Zhang et al., 2018), which undoubtedly increases the cost of POCT. Hence, noble-metals-free nanomaterials are considered to be the next generation of alternative sensors. As one of the Earth-abundant elements, sulfur finds a prominent place in various applications with diverse morphology, including nano, micro, and bulk states (Boyd, 2016, Teng et al., 2019). Among the reported applications, the nano-sized sulfur quantum dots (S dots) procure an edge on chemical sensing (Arshad and Sk, 2020, Liu et al., 2020), white light-emitting diodes (Wang et al., 2019), and cellular imaging (Qiao et al., 2020, Zhang et al., 2019) for their attractive optical property, desirable photostability, low toxicity, and superior dispersibility. However, there has been no attempt to design the S dots as a portable optical sensor for POCT. With the assistance of PEG-400 and NaOH, Zhang’s group successfully prepared the S dots with good water solubility from sublimated sulfur powder (Shen et al., 2018). At the same time, the disposable PAD is usually hydrophilic due to the abundance of –OH groups from cellulose (Kurdekar et al., 2016). Therefore, the S dots will easily infiltrate the filter paper, greatly reducing the time required for S dots to cover the detection area. From an economical cost and time saving point of view, S dots are a good choice for the PAD-based POCT platform.

Herein, we proposed a disposable PAD based on the S dots for POCT of four metal ions (Fe³⁺, Co²⁺, Pb²⁺, and Cd²⁺) detection. Considering that these four metal ions combined with S dots produce different visual signals (Fe³⁺: from colorless to green; Co²⁺: from colorless to brown; Cd²⁺: from colorless to bright yellow; Pb²⁺: from colorless to precipitation), in addition to the ultraviolet-visible (UV–vis) absorption, the corresponding color evolution can be used as a readout signal (HSV color model) to monitor the metal ions. As shown in Scheme 1, we designed and fabricated a three-layer PAD with several assay spots that a scanner can easily capture. The obtained images can be subsequently analyzed through the image processing software (ColorColl App) on a smartphone for visual and on-site sensing of metal ions. Moreover, the logic gate is a functional data processing device that allows logical calculations to perform when various signals are input (Zou et al., 2018). Therefore, it is possible to create molecular-scale computers and “autonomously regulated” chemical systems (Huang et al., 2011, Lee et al., 2021, Park et al., 2010). Through defining multi-input (Fe³⁺, Co²⁺, Pb²⁺, and Cd²⁺) and multi-readout signals (different colors and precipitation), we further constructed the multi-coding logic gates (YES, NOT, AND, INHIBIT, and NOR) based on the metal ions-induced S dots discrimination platform. This platform allows for flexible functional switching among the proposed logic gates via simply altering these input groups (metal ions) and defining different output signals. Compared with the existing logic gate with single input and output, this quadruple analyte responsive platform is beneficial for realizing large-scale molecular logic computation. Accordingly, the S dots-based platform shows remarkable versatility, enabling quadruple chemical sensing and advanced information processing by simply reading four independent visual signals. This strategy displays strong potential for S dots in developing on-site environmental monitoring and designing intelligent molecular engineering.