Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors

Abstract

Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive methods to detect EDCs, which are detrimental even at very low concentrations. In this work, we propose a label-free surface plasmon resonance (SPR) biosensor method to detect specific EDCs (17 β-estradiol (E2), ethinyl-estradiol, 4-nonylphenol, tamoxifen) through their binding to estrogen receptor alpha (ERα). We show that the use of rationally designed ERα (as bio-recognition element) in combination with conformation-sensitive peptides (as amplification agent, resulting in increased responses) enables the detection of low parts per billion (ppb) levels of E2. As a proof of concept, this bioassay was used to detect E2 in (spiked) real water samples from fish farms, rivers and the sea at low ppb levels after concentration by solid phase extraction. In addition, the present SPR assay that combines a conformation-sensitive peptide with an array of ERα mutants is very promising for the assessment of the risk of potential estrogenic activity for chemical substances.

Critical parameters in surface plasmon resonance biosensor development: The interaction between estrogen receptor and estrogen response element as model

“…The resulting test facilitates the evaluation of endocrine disrupting chemicals. It can also be applied in environmental monitoring as this method reached a detection limit of 5 nM of E2 [1], which is consistent with the detection limit of other biosensors involving SPR [18,22,23] and is below the detection limit of biosensors based on other technologies [24,25].…”

Ultrasensitive detection of endocrine disruptors via superfine plasmonic spectral combs

“… Transducer used Quantitative range (ng ml −1 ) LOD (ng ml −1 ) Ref. Electrochemical / / 6 Fluorescent / / 13 Fluorescent 20.8–476.7 1.05 14 Fluorescent 0.1–20 0.1 48 Piezoelectric 2.72–27.2 2.12 18 Nonisotopic / 0.2 10 Surface plasmon resonance 2–6 0.2 15 Surface plasmon resonance / 1 49 Surface plasmon resonance / 1.4 50 Surface plasmon resonance 0.01–100 0.0015 This work Note: “/” means undetectable or not available. …”

“…To date, numerous nER-based biosensors have been developed by using different signal transductions modes, such as fluorescence 14 , surface plasmon resonance (SPR) 15 – 17 , piezoelectric 18 , and electrochemistry 19 , 20 . These cell-free biosensors are cost-effective and robust to the cytotoxicity of environmental samples.…”

Advances in Electrochemical Impedance Spectroscopy Detection of Endocrine Disruptors

“…Human-estrogen receptor alpha (ER-α) is a protein that belongs to the nuclear receptor group and can bind xenoestrogens such as 17β-estradiol. Due to its specificity and ability to be engineered, ER-α was used as bio-recognition element for the development of ED detection methods [ 86 ]. Estrogen receptor-based biosensors are not often encountered, but it is worth mentioning some notable works ( Table 6 ).…”