A Highly Selective Turn-On Biosensor for Measuring Spermine/Spermidine in Human Urine and Blood

Abstract

Spermine and spermidine serve as the key biomarkers for early-stage cancer diagnosis. This work reports a rapid, highly selective, and noninvasive sensing platform for spermine/spermidine. The hybrid material, developed in this work, has been characterized by UV–vis, IR, powder XRD, SEM, EDX, and rheological studies. Storage modulus (G′) and loss modulus (G″) measurements infer that embedding boronic acid integrated coumarin softens the agarose gel fibers at room temperature. Stress resistance measurement and subsequent imaging further confirms the softness of the hybrid hydrogel over pure agarose gel and homogeneous distribution of the dye in the hybrid matrix as well. The soft hydrogel with a limit-of-detection (LOD) value of 6 μM showed a nearly 27-fold fluorescence enhancement for spermine. The hybrid hydrogel matrix can be useful within a wide concentration window (6 μM–2.5 mM spermine). Response time (≤7 s) confirms rapid detection ability of the material. Noninterference from various metal ions, common anions, monosaccharides, nucleobases, and amino acids, particularly, histidine, arginine, lysine, ornithine, glutamine, etc., makes the hybrid hydrogel suitable for the real-time measurement of spermine in human urinary and blood samples. Furthermore, noninterference from other biogenic amines supports the highly selective nature of the hybrid gel. The ability to measure spermine in urinary samples by the probe offers a noninvasive nature of the sensing platform. Overall, we envisioned that the hybrid material formulation would be useful for diagnosing early-stage tumors and assessing the recovery of patients undergoing chemotherapeutic treatment.

Hydrogel‐based composites: Unlimited platforms for biosensors and diagnostics

“…Combining the versatile functional properties of the hydrogel matrices and filler materials, assisted by the various electrical/optical transducing strategies, highly sensitive, selective, and reliable detection of chemical biomarkers in blood [ 97,231,232 ] and urine, [ 120,233,234 ] and other physical signals [ 63,235,236 ] have been demonstrated over the past years, as summarized in Table 1. In this section, we will describe the applications of hydrogel composite‐based biosensors for health monitoring and disease diagnosis.…”

“…[ 57,107,265 ] The diagnosis of cancer is achieved through the detection of certain biomarkers, such as nucleic acids, [ 60,266–268 ] proteins, [ 269–272 ] and amines. [ 233 ]…”

“…Due to the specific interaction between CB and spermine/spermidine, this sensing platform exhibited highly sensitive and selective spermine/spermidine responses, for example, with a low limit of detection of 6 μM over a wide detection range of 6 μM to 2.5 mM for spermine. [ 233 ]…”

Solid-Supported Amplification of Aggregation Emission: A Tetraphenylethylene–Cucurbit[6]uril@Hydroxyapatite-Based Supramolecular Sensing Assembly for the Detection of Spermine and Spermidine in Human Urine and Blood

“…Encouraged by these facts, a variety of chemosensors 17 for spermine and spermidine have been developed based on fluorimetry, mainly adopting various supramolecular approaches. 18−29 This includes dye-embedded micelles, 18,19 sol−gel films, 20,21 conjugated polymers, 22−27 and other supramolecular approaches. 28,29 A close look at most of these reports suggests that selectivity of these polyamines is based on analyte-induced self-assembly of the reporting units to amplify the sensing response.…”

“…Spermine (SP) and spermidine (SPD) are the most ubiquitous among biogenic polyamines (PAs) and they are important regulators of various cellular processes including cell growth, proliferation, homeostasis, and even protein biosynthesis. − They are also involved in metabolic regulation, regeneration of intestinal mucosa, and wound healing, especially at low concentrations. − However, elevated levels of these amines are responsible for aging and symptomatic of anomalous biological progressions concomitant with cancer. − Spermine/spermidine is investigated as a biochemical marker for the timely diagnosis of cancer. ,, The presence of spermine and spermidine is also measured as an indicator of the quality of food, as their concentration surges due to fermentation or decomposition, which leads to health issues. , In addition, at higher concentrations, these PAs cause food spoilage and food poisoning. , Thus, the development of selective and sensitive detection tools for these biogenic polyamines is of great importance for the early diagnosis of diseases as well as the maintenance of food hygiene. Encouraged by these facts, a variety of chemosensors for spermine and spermidine have been developed based on fluorimetry, mainly adopting various supramolecular approaches. − This includes dye-embedded micelles, , sol–gel films, , conjugated polymers, − and other supramolecular approaches. , A close look at most of these reports suggests that selectivity of these polyamines is based on analyte-induced self-assembly of the reporting units to amplify the sensing response. However, they suffer from one or more limitations such as interference from other polyamines, susceptibility to external stimuli (e.g., light, heat), and also not well explored under physiological condition.…”