Multianalyte Sensors Research Articles

Electrochemical Analysis of Key Anticancer Herbal Drugs: Progress and Innovations in Emodin, Rutin, Berberine, Shikonin, and Sophoridine

Background: Anticancer herbal drugs have gained significant attention in pharmaceutical research due to their complex chemical profiles and multifaceted therapeutic effects. Electrochemical analysis has emerged as a powerful tool for studying these compounds, offering unique insights into their behavior and properties. Methods: This review examines recent advances in the electrochemical analysis of five key anticancer herbal drugs: emodin, rutin, berberine, shikonin, and sophoridine. Various electrochemical techniques, including cyclic voltammetry, differential pulse voltammetry, and square wave voltammetry, are discussed in relation to their application in detecting and characterizing these compounds. Results: Significant progress has been made in developing highly sensitive and selective electrochemical sensors for these herbal drugs. Nanomaterial-modified electrodes have consistently improved detection limits and expanded linear ranges. Compound-specific innovations in electrode modifications and measurement techniques have been tailored to the unique electrochemical properties of each drug. Conclusion: Electrochemical analysis of anticancer herbal drugs has advanced substantially, offering powerful tools for studying and utilizing these compounds in cancer research and treatment. Future directions include the development of multi-analyte sensors, integration with microfluidic technologies, and application of artificial intelligence for data analysis. Challenges remain in improving the stability of modified electrodes and standardizing protocols for sample preparation and analysis.

Hybrid graphene nanoflakes for electrochemical sensing with multianalyte detection capability

This work illustrates the production of highly electrochemically active graphene by liquid phase exfoliation technique for ultrasensitive electrochemical sensors. An airless high-pressure spray technique was designed to exfoliate bulk natural graphite into nm-scaled flakes (referred as HP50). Transmission electron microscopy, Raman and X-ray photoelectron spectroscopy studies reveal that the HP50 sample has a mixed structure composed of amorphous carbon and a few-layer graphene fraction with high amount of edge plane defects. The HP50 flakes are drop cast on glassy carbon electrodes to test the simultaneous and selective electrochemical detection of hydrogen peroxide, ascorbic acid, and dopamine. In cyclic voltammetry measurements, hydrogen peroxide reduces at −0.2 V vs Ag/AgCl (1 M), while ascorbic acid and dopamine oxidize at 0.1 V vs Ag/AgCl (1 M) and 0.3 V vs Ag/AgCl (1 M), respectively. Linear sweep voltammetry demonstrates high sensitivity (164, 739, and 3357 μA mM−1 cm−2) and low limit of detection (15, 1.7, and 2.1 μM) for the three analytes, respectively. Interference studies confirm a high sensitivity and selectivity towards the different chemical species. The HP50-based multianalyte sensors are also tested against different environmental and commercial samples, illustrating their viability in practical applications.

Beyond Glucose Monitoring: Multianalyte Sensor Use in Diabetes.

The incidence, prevalence, mortality, and health expenditure associated with diabetes continue to grow, despite efforts. The use of multianalyte sensors, which detect glucose as well as key analytes such as ketones, lactate, insulin, uric acid, and electrolytes, may provide additional information to guide earlier identification and management of diabetes and its complications. We undertook a narrative review using a systematic approach in May 2023, with a bridge search undertaken in April 2024. Four biomedical databases were searched: MEDLINE (Ovid), Embase, Emcare, and Cochrane Library. Searches for gray literature were conducted on ClinicalTrials.gov, Google Scholar, and websites of relevant organizations. Included studies incorporated articles on multianalyte sensors in diabetes and single-analyte sensors proposing integration into multianalyte diabetes management, with no limits placed on publication date and study design. Data were screened and extracted using CovidenceTM software. Overall, 11 articles were included, of which 7 involved multianalyte sensors (involving glucose and other analytes) and 4 single-analyte sensors (measuring non-glucose substances for proposed future integration into multianalyte systems). Analytes examined were ketones (n = 3), lactate (n = 4), uric acid (n = 3), insulin (n = 1), and potassium (n = 1). Results demonstrated that in vitro and invivo measurements of multi- and single-analyte sensors accurately and reliably corresponded with human capillary and serum samples. While the literature on this topic is sparse, our review demonstrated that measurement of glucose and other analytes can be feasibly undertaken using multi- and single-analyte sensors. More studies in humans are needed to establish clinical utility in diabetes self-management and assist with technological improvements.

Photoswitchable Rhodamine‐Based Multianalyte Sensors for Metal Ion Detection

AbstractWe have developed three azobenzene‐core‐based molecular systems decorated with different numbers of rhodamine units as photoswitchable multianalyte sensors. Exploiting the ring‐opening of the spirolactam part of the rhodamine unit, the resulting fluorescence response, and modulation of it through the photoswitching of azobenzene by light, we utilized them in the detection of multiple metal ions (Fe3+, Fe2+, Sn2+ and Al3+). The binding sites, stoichiometry, binding constants, fluorescent lifetimes and limit of detection (LOD) for each probe have been deduced using appropriate spectroscopic techniques. The limit of detection (LOD) of 5 a, 5 b and 5 c for Fe3+ are found to be 4.2×10−7±7.8×10−9 M, 2.2×10−7±4.6×10−9 M and 1.2×10−7±4.6×10−9 M, respectively. The fluorescence response of the metal‐chelated complex can be manipulated effectively by employing the photoswitching ability of azobenzene that makes them useful as chemosensors for various individual metal ions.

Oxygen vacancies boosted vanadium doped ZnO nanostructures-based voltage-switchable binary biosensor

The development of a reliable non-enzymatic multi-analyte biosensor is remained a great challenge for biomedical and industrial applications. In this prospective, rationally designed electrode materials having voltage switchable electrocatalytic properties are highly promising. Here, we report vanadium doped ZnO engineered nanostructures (Zn1−x V x O where 0 ≤ x ≤ 0.1) which exhibit voltage switchable electrocatalytic properties for accurate measurements of glucose and hydrogen peroxide. Microstructures and chemical analysis show that the oxygen vacancies in the material can be tuned by controlling the stoichiometric ratios which play key role for voltage dependent measurements of different analytes. The developed Zn1−x V x O nanostructures exhibit outstanding sensing ability for binary analytes with a high selectivity, low detection limit, thermal stability and long-term stability. The Zn0.9V0.1O/glassy carbon (GC) electrode shows 3-fold increase in reproducible sensitivity for both glucose (655.24 μA mM−1 cm−2) and H2O2 (13309.37 μA mM−1 cm−2) as compared to the pristine ZnO/GC electrode. Moreover, the electrode also shows good response for human blood serum and commercially available samples. The results demonstrate that defect engineering is a promising route for the development of cost-effective non-enzymatic multi-analyte sensors for practical applications.

A dual signal on-off fluorescent nanosensor for the simultaneous detection of copper and creatinine.

The transition of conventional medicine to personalized medicine has paved the way for sensing new biomolecules. Consequently, this field attracted wide interest due to its capability to provide information on point of care basis. Multi-analyte sensors that emerged recently can perform quick and affordable analysis with minimum quantity of blood samples compared to traditional sensing of individual analytes. The present study focuses on the development of a quantum dot (Qd) based nanosensor for the simultaneous detection of copper and creatinine; two biologically relevant molecules. The sensor was designed by forming a complex of Qd with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and picric acid through carboxylic bond formation of Qd-EDC with picric acid. The dual independent emissions of the Qd-EDC complex was used for the simultaneous detection of creatinine and copper by a turn on/turn off method and was successfully demonstrated with a sensitivity of nanomolar to millimolar, and micromolar to millimolar range respectively. The multianalyte sensor thus developed has quick response and works well under normal conditions of temperature and pH. It is also shown to work in cellular environment and blood serum. A simple image based detection of creatinine using the sensor strips has also been attempted by means of a mobile camera and validated with human blood samples.

Cd(II) enhanced fluorescence and Zn(II) quenched fluorescence with phenylenevinylene terpyridine: A theoretical investigation.

Phenylenevinylene terpyridine (mepvpt) shows chelation enhanced fluorescence (CHEF) with Cd(II) and chelation quenched fluorescence (CHQF) with Zn(II), respectively. To understand the behaviors, we studied their intrinsic optical properties using DFT/TDDFT methods. The results show that fluorescence quantum yields (FQY) of mepvpt, mepvpt-Cd and mepvpt-Zn are low due to high ISC rates from higher excited states rather than the S1 excited state. When mepvpt chelates Cd(II), the molecular structure becomes more planar and S3,4 → S0 radiation rates become higher than that of mepvpt, which results in CHEF. When mepvpt chelates Zn(II), a new S4 → S0 emission with low oscillator strength occurs and high S4 → Tn ISC rates appear, which leads to CHQF. This proposed mechanism of metal fluorescence enhancing/quenching suggests a design strategy for single-molecular multi-analyte sensors.

Characterization of Lactate Sensors Based on Lactate Oxidase and Palladium Benzoporphyrin Immobilized in Hydrogels.

An optical biosensor for lactate detection is described. By encapsulating enzyme-phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive emission lifetimes were achieved. The relative amount of monomer was varied to compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate) (pHEMA) and two copolymers of pHEMA and poly(acrylamide) (pAam). Diffusion analysis demonstrated the ability to control lactate transport by varying the hydrogel composition, while having a minimal effect on oxygen diffusion. Sensors displayed the desired dose-variable response to lactate challenges, highlighting the tunable, diffusion-controlled nature of the sensing platform. Short-term repeated exposure tests revealed enhanced stability for sensors comprising hydrogels with acrylamide additives; after an initial “break-in” period, signal retention was 100% for 15 repeated cycles. Finally, because this study describes the modification of a previously developed glucose sensor for lactate analysis, it demonstrates the potential for mix-and-match enzyme-phosphor-hydrogel sensing for use in future multi-analyte sensors.

Exceptional Oxygen Sensing Properties of New Blue Light-Excitable Highly Luminescent Europium(III) and Gadolinium(III) Complexes.

New europium(III) and gadolinium(III) complexes bearing 8-hydroxyphenalenone antenna combine efficient absorption in the blue part of the spectrum and strong emission in polymers at room temperature. The Eu(III) complexes show characteristic red luminescence whereas the Gd(III) dyes are strongly phosphorescent. The luminescence quantum yields are about 20% for the Eu(III) complexes and 50% for the Gd(III) dyes. In contrast to most state-of-the-art Eu(III) complexes the new dyes are quenched very efficiently by molecular oxygen. The luminescence decay times of the Gd(III) complexes exceed 1 ms which ensures exceptional sensitivity even in polymers of moderate oxygen permeability. These sensors are particularly suitable for trace oxygen sensing and may be good substitutes for Pd(II) porphyrins. The photophysical and sensing properties can be tuned by varying the nature of the fourth ligand. The narrow-band emission of the Eu(III) allows efficient elimination of the background light and autofluorescence and is also very attractive for use e.g. in multi-analyte sensors. The highly photostable indicators incorporated in nanoparticles are promising for imaging applications. Due to the straightforward preparation and low cost of starting materials the new dyes represent a promising alternative to the state-of-the-art oxygen indicators particularly for such applications as e.g. food packaging.

Coupled Tamm waves guided by an isotropic and homogeneous dielectric layer in a rugate filter

The propagation of Tamm waves (also known as Bloch surface waves) guided by a layer of homogeneous dielectric material in a rugate filter was studied theoretically. A canonical boundary-value problem was set up and a dispersion equation was obtained. The solution of the dispersion equation indicated the existence of coupled modes of Tamm waves that were absent when the homogeneous dielectric material was taken to occupy a half space. The spatial profiles of the electric and magnetic fields of Tamm waves showed that Tamm waves propagate localized to either one or both interfaces. Multiple Tamm waves may lead to multi-analyte chemical sensors and multi-channel communication.

Tailoring Sol–Gel-Derived Silica Materials for Optical Biosensing

The last two decades have seen a revolution in the area of sol–gel-derived materials as media for the immobilization of biomolecules for biosensor fabrication. Such materials are suitable for the entrapment of a range of biomolecules, from enzymes to antibodies and even functional nucleic acids (FNA) such as aptamers and DNA enzymes. Recent progress in the development of “protein friendly” sol–gel processing methods has allowed these materials to be utilized as components of numerous biosensors, using delicate biomolecules such as luciferease and kinases, or even membrane-bound receptors as biorecognition elements. In addition, such materials have proven to be particularly versatile in the fabrication of biosensors, being amenable to methods such as dipcasting, contact printing, or even noncontact inkjet printing to form a bioselective coating on a range of substrates. In this review, we provide an overview of advances in biofriendly sol–gel processing methods developed in our research group and others, and we highlight accomplishments in the immobilization of both proteins and FNA within silica based materials. We then describe methods for interfacing biomolecule-doped materials to optical biosensors, with emphasis on fiber optic sensors, microarray-based multianalyte sensors and bioactive paper-based test strips. In each case, the material processing requirements for fabrication of different devices is emphasized. Finally, a brief perspective on potential future areas of research in the field of sol–gel based biocomposites is provided.

A Conductometric Indium Oxide Semiconducting Nanoparticle Enzymatic Biosensor Array

We report a conductometric nanoparticle biosensor array to address the significant variation of electrical property in nanomaterial biosensors due to the random network nature of nanoparticle thin-film. Indium oxide and silica nanoparticles (SNP) are assembled selectively on the multi-site channel area of the resistors using layer-by-layer self-assembly. To demonstrate enzymatic biosensing capability, glucose oxidase is immobilized on the SNP layer for glucose detection. The packaged sensor chip onto a ceramic pin grid array is tested using syringe pump driven feed and multi-channel I–V measurement system. It is successfully demonstrated that glucose is detected in many different sensing sites within a chip, leading to concentration dependent currents. The sensitivity has been found to be dependent on the channel length of the resistor, 4–12 nA/mM for channel lengths of 5–20 μm, while the apparent Michaelis-Menten constant is 20 mM. By using sensor array, analytical data could be obtained with a single step of sample solution feeding. This work sheds light on the applicability of the developed nanoparticle microsensor array to multi-analyte sensors, novel bioassay platforms, and sensing components in a lab-on-a-chip.

Screening of π-Basic Naphthalene and Anthracene Amplifiers for π-Acidic Synthetic Pore Sensors

Synthetic ion channels and pores attract current attention as multicomponent sensors in complex matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes and drag them into the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because aromatic electron donor-acceptor (AEDA) interactions account for their recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged amplifiers with submicromolar activity.

Fluorometric Detection of Inositol Phosphates and the Activity of Their Enzymes with Synthetic Pores: Discrimination of IP7 and IP6 and Phytate Sensing in Complex Matrices

We report the fluorometric and noninvasive detection of inositol phosphates, which act as privileged blockers of synthetic pores. Phytate (IP6) and IP7 recognition in the pore occurs substoichiometrically in the low nanomolar range, with more than 2 orders of magnitude higher sensitivity than the best available alternative. Zn2+-mediated fluorometric discrimination between IP6 and IP7 demonstrates that significant pore discrimination challenges can be solved with judiciously selected additives. The detectability of inositol phosphate enzyme activity was exemplified with phytase. Phytate sensing was accomplished in complex matrices such as extracts from almonds, soybeans, or lentils, using phytase as a specific signal generator. These results are important because they not only add essential evidence in support of the usefulness of synthetic pores as multianalyte sensors in complex matrices but also reveal the existence of privileged analytes that can provide access to submicromolar sensitivity without the...

A Simple Method for Preparing Spectrally Encoded Magnetic Beads for Multiplexed Detection

This report describes a simple method for preparing encoded microspheres for use in multiplexed biological detection. In this method, hydrophobic trioctylphosphine oxide (TOPO)-capped CdSe@ZnS quantum dots (QDs) are assembled on polyamine-coated microspheres in chloroform and encapsulated in an outer shell of silica nanoparticles functionalized with a specific recognition surface. Because TOPO-capped QDs are assembled instead of their water-soluble equivalents, the microspheres are highly luminescent. The amount of QDs assembled depends only on the surface area of the substrate, and therefore, the photoluminescence intensity increased uniformly in proportion to the number of QD layers assembled. The outer shell of silica nanoparticles confers stability on the assembled QDs but has no effect on their photoluminescence because it is transparent to excitatory and emitted light. It was activated with aminosilane and functionalized with a recognition surface of protein antigens using disulfide exchange chemistry. Magnetic beads furnished with spectral codes of up to three colors of QDs matched to specific recognition surfaces were used as multianalyte sensors for serum proteins.

Synthetic Multifunctional Nanoarchitecture in Lipid Bilayers: Ion Channels, Sensors, and Photosystems

Abstract The creation of functional materials such as ion channels, porous sensors, or smart photosystems depends critically on our ability to assemble sophisticated, error-free and self-repairing nanoarchitecture in a predictable manner. To address these challenging topics, we often used lipid bilayer membranes as compartmentalizing platform and have introduced rigid-rod molecules as privileged scaffolds that bypass all folding problems because they do not fold. This approach provides access to motifs such as rigid-rod barrels, helices, stacks, slides, and wires that can act as smart, stimuli-responsive photosystems, pores, ion channels, hosts, sensors, and catalysts. The selected examples focus on naphthalenediimides (NDIs), a compact, organizable, colorizable, and functionalizable n-semiconductor. This versatile module is used in rigid-rod molecules to mediate transmembrane anion transport by anion–π interactions, as sticky π-clamp within pore sensors to catch otherwise elusive analytes by aromatic electron donor–acceptor interactions, or in blue, transmembrane π-stack architecture to collect and convert photonic energy. These specific examples with multifunctional NDI nanoarchitecture are of help to outline, on the one hand, possibilities to contribute to advanced functional materials such as multianalyte sensors or solar cells and, on the other hand, to keep on wondering about an enormous structural and functional space waiting to be explored.

Synthetic pores with sticky π-clamps

In this report, we describe design, synthesis, evaluation and molecular dynamics simulations of synthetic multifunctional pores with pi-acidic naphthalenediimide clamps. Experimental evidence is provided for the formation of unstable but inert, heterogeneous and acid-insensitive dynamic tetrameric pores that are sensitive to base and ionic strength. Blockage experiments reveal that the introduction of aromatic electron donor-acceptor interactions provides access to the selective recognition of pi-basic intercalators within the pore. This breakthrough is important for the application of synthetic pores as multianalyte sensors.

Microfabricated protein-containing poly(ethylene glycol) hydrogel arrays for biosensing

We describe the use of poly(ethylene glycol) (PEG) hydrogel microstructures containing immobilized enzymes such as acetylcholinesterase (AChE) and urease for the detection of analytes. Changes in the microenvironment pH due to enzyme-catalyzed reaction with the analyte of interest were used to fluorescently detect low concentrations of the analyte. The hydrogel microstructures were prepared photolithographically on silicon surfaces. The use of a microarraying robot to create microstructured hydrogel array sensors is also described. A dual analyte sensor using this scheme is presented to demonstrate the ease of creation of such multianalyte sensors. Such micron-sized arrays can therefore be easily used as biosensors to detect small molecular weight analytes to extremely low concentrations in air or water.

Simultaneous multi-analyte determination of estrone, isoproturon and atrazine in natural waters by the RIver ANAlyser (RIANA), an optical immunosensor

In most medical and environmental applications of biosensors, only single analytes are determined. However, the monitoring of several analytes is obviously preferable in order to gather more information about the sample under analysis. In line with this, different technologies are being developed to obtain multi-analyte sensors. In this paper, an analytical method for the simultaneous determination of three different contaminants—atrazine, isoproturon, and estrone—in natural waters by using an optical immunosensor prototype, the so-called “RIver ANAlyser” (RIANA), is described. RIANA is based on a rapid solid-phase fluoroimmunoassay that takes place at an optical transducer chip. The transducer surface is chemically modified with three analytes derivatives placed in different discrete locations. The sensor surface can be regenerated thus allowing the performance of several measurements with the same transducer. Each test cycle, including one regeneration step, is accomplished in 15 min. Detection limits achieved were 0.155, 0.046, and 0.084 μg/l, for atrazine, isoproturon, and estrone, respectively. Satisfactory repetition, with relative standard deviations between 1.06 and 6.98%, was obtained. Excluding a minor non-specifical binding of the isoproturon antibodies, no cross-reactivity effects were observed. Matrix effects were significant only in the case of wastewater samples. Biosensor measurements were validated using conventional liquid chromatography-mass spectrometry. The results obtained with both techniques were in good agreement.

Electrochemical impedance spectroscopy as a platform for reagentless bioaffinity sensing

Simple reagentless immunosensor formats have been difficult to achieve, particularly for electrochemical devices, since antigen/hapten recognition by an antibody does not directly lead to a reaction cascade. A direct reading electrochemical immunosensor would have major advantages with respect to speed, de-skilled analysis and the development of multi-analyte sensors. Electrically conducting polymers, such as poly(pyrrole), allow for the intimate association between a biological recognition element and a potential reporter polymeric chain. We have polymerised poly(pyrrole), loaded with avidin or antibody to luteinising hormone (LH), on gold interdigitated electrodes (IDE) and employed two-electrode electrochemical impedance spectroscopy (EIS) to “visualise” charge transfer through the polymer as the basis for a reagentless protocol. We investigated bulk redox processes in the poly(pyrrole) films by cyclic voltammetry in order to ascertain the redox state of the film prior to EIS. The redox process of the immobilised protein molecule was identified and allowed the focusing of the EIS studies on polymer associated with the immobilised bioaffinity molecule. The polymer displayed both polaronic and electronic charge transfer during EIS studies. A possible binding-dependent response, observed as a decrease in peak polaronic phase angle, occurred when a redox cycle was performed on the film following exposure to the appropriate analyte. The response of poly(pyrrole) films loaded with avidin to d-biotin and two derivatives was assessed, which was shown to be sensitive to electrode pre-treatment. Poly(pyrrole) films loaded with antibody to LH allowed a calibration for LH to be constructed between 1 and 800 IU/l. Importantly, the films were responsive to LH within the clinically relevant range of 1–10 IU/l.