Photoelectrochemical Cytosensor Research Articles

Responsive Nd-MOF nanorods based near-infrared photoelectrochemical cytosensor and real-time monitoring HClO releasing from cells and tumor

Designing functionalized MOFs with specific reactivity and NIR photoelectrochemical and fluorescent response is critical for developing biosensing systems. Herein, SCy7, a conjugate macrocycle ligand with a specific fluorescence responsive group to HClO, was designed and synthesized. Responsive Nd-MOF nanorods were successfully prepared by using SCy7 as the organic ligand and Nd3+ as the metal central ion. Nd-MOF nanorods show good absorption characteristics in the wavelength range of 200–1200 nm with a band gap of 0.89 eV. Nd-MOF nanorods were employed as a photoactive material to construct a near-infrared photoelectrochemical cytosensor for MCF-7 cells by integrated with an aptamer. The photocurrent variation exhibits a good linear response to MCF-7 cells in the concentration range of 50–1.0 × 107 cells mL−1, and a comparatively low detection limit of 18 cells mL−1 (S/N = 3). The NIR PEC cytosensor was also employed for monitoring endogenous HClO released from MCF-7 cells as being stimulated by PMA. HClO is an electron acceptor that can convert the anodic photocurrent into cathodic photocurrent, thus achieving monitoring HClO through the conversion of photocurrent polarity. Furthermore, Nd-MOF was coated with F127 to improve its hydrophilicity and biocompatibility, and to provide a Nd-MOF@F127 with a fluorescence emission peak at 830 nm. Nd-MOF@F127 show specific fluorescence response to HClO, and thus was successfully used in imaging HClO variation in cells and breast cancer bearing mice.

A photoelectrochemical cytosensor based on a Bi2S3-MoS2 heterojunction-modified reduced oxide graphene honeycomb film for sensitive detection of circulating tumor cells.

A novel photoelectrochemical (PEC) cytosensor for the ultrasensitive detection of circulating tumor cells (CTCs) was developed. The bio-inspired reduced graphene oxide (rGO) honeycomb film photoelectrode was fabricated via a "breath figure" method, followed by the self-assembly of a Bi2S3-MoS2 heterojunction. The resulting Bi2S3-MoS2 heterojunction-modified rGO honeycomb film was employed as a sensing matrix for the first time. Compared to the smooth rGO film, the significant enhanced photocurrent of the photoelectrode under visible light was attributed to its improved visible light absorption, increased surface area and enhanced separation efficiency of photo-generated electron-hole pairs, which met the requirements of the PEC sensor for detecting larger targets. By virtue of the photocurrent decrease due to the steric hindrance of MCF-7 cells, which were captured by an aptamer immobilized on the surface of the photoelectrode, a cytosensor for detecting CTCs was achieved, showing a wide linear range of 10-1 × 105 cells per mL and a low detection limit of 2 cells per mL. Furthermore, MCF-7 cells in human serum were determined by this PEC biosensor, exhibiting great potential in the clinical detection of CTCs.

Ultrasensitive PEC cytosensor for breast cancer cells detection and inhibitor screening based on plum-branched CdS/Bi2S3 heterostructures

Breast cancer is the most common malignant tumor in women, which seriously threatens the life and health of patients. Therefore, facile and sensitive detection of human breast cancer cells is crucial for cancer diagnosis. In this work, plum-branched CdS/Bi2S3 heterostructures (CdS/Bi2S3 HSs) were synthesized under hydrothermal condition, whose photoelectrochemical (PEC) property and biocompatibility were scrutinously investigated. In parallel, a signal amplification strategy was designed based on immune recognition between epidermal growth factor receptor (EGFR) overexpressed on membrane of breast cancer cells MDA-MB-231 and its aptamer. Integration of the above together, a highly sensitive PEC cytosensor was developed for analysis of target MDA-MB-231 cells, exhibiting a wider linear range of 1 × 102 ∼ 3 × 105 cells mL−1 with a limit of detection (LOD) down to 6 cells mL−1 (S/N = 3). Further, the biosensor was explored for anticancer drug (e.g., dacomitinib) screening by monitoring the variations in the PEC signals of the expressed EGFR upon drug stimulation. The obtained CdS/Bi2S3 HSs are identified as promising and feasible photoactive material for determination of cancer cells and drug screening in clinic and related research.

Novel Aggregation-Enhanced PEC Photosensitizer Based on Electrostatic Linkage of Ionic Liquid with Protoporphyrin IX for Ultrasensitive Detection of Molt-4 Cells.

Nowadays, aggregation quenching of most organic photosensitizers in aqueous media seriously restricts analytical and biomedical applications of photoelectrochemical (PEC) sensors. In this work, an aggregation-enhanced PEC photosensitizer was prepared by electrostatically bonding protoporphyrin IX (PPIX) with an ionic liquid of 1-butyl-3-methylimidazole tetrafluoroborate ([BMIm][BF4]), termed as PPIX-[BMIm] for clarity. The resultant PPIX-[BMIm] showed weak photocurrent in pure dimethyl sulfoxide (DMSO, good solvent), while the PEC signals displayed a 44.1-fold enhancement in a water (poor solvent)/DMSO binary solvent with a water fraction (fw) of 90%. Such PEC-enhanced mechanism was critically studied by electrochemistry and density functional theory (DFT) calculation in some detail. Afterward, a label-free PEC cytosensor was built for ultrasensitive bioassay of acute lymphoblastic leukemia (molt-4) cells by electrodepositing Au nanoparticles (Au NPs) on the PPIX-[BMIm] aggregates and sequential assembly of protein tyrosine kinase (PTK) aptamer DNA (aptDNA). The resultant cytosensor showed a wide linear range (300 to 3 × 105 cells mL-1) with a limit of detection (LOD) as low as 63 cells mL-1. The aggregation-enhanced PEC performance offers a valuable and practical pathway for synthesis of advanced organic photosensitizer to explore its PEC applications in early diagnosis of tumors.

Renewable photoelectrochemical cytosensing platform for rapid capture and detection of circulating tumor cells

Determination of circulating tumor cells (CTCs) is crucial for cancer diagnosis and therapy at an early stage. However, extremely low concentration of CTCs in peripheral blood makes the detection of CTCs challenging. In this study, a reusable cytosensor was developed for rapid detection of CTCs based on excellent photoelectrochemical (PEC) characteristic of semiconductor nanoarrays. Using typical breast cancer cell, MCF-7 cell, as a target model, a PEC sensing platform was constructed with polymerized aminophenylboronic acid (APBA) layer coated CdS/ZnO nanorod arrays, exhibiting outstanding performance for the capture and detection of CTCs. In this design, the polymerized APBA provides abundant binding sites for capturing terminal sialic acid (SA) molecules in CTCs. As a result, the PEC cytosensor shows good sensitivity and specificity with concentrations ranging from 50 to 1.0 × 106 cells/mL MCF-7 cells. Moreover, the PEC cytosensor can be rapidly and effectively recovered via a short-time bias triggered cell release and subsequent repair of APBA. This study establishes a new approach to refine a PEC cytosensor for stable monitoring and provides a robust PEC electrode with high sensitivity and low cost for clinical diagnosis related to CTCs.

In-situ synthesis of covalent organic polymer thin film integrates with palladium nanoparticles for the construction of a cathodic photoelectrochemical cytosensor

Sensitive detection of cancer cells is essential to early clinic diagnosis, and the photoelectrochemical (PEC) sensors with high sensitivity and good selectivity may provide new approaches for cytosensing. Herein, we demonstrate the development of a new cathodic PEC cytosensor based on the integration of covalent organic polymer (COP) with palladium nanoparticles (PdNPs). The COP films are in-situ grown at room temperature on the transparent indium tin oxide-coated glass substrates, and they subsequently assemble with PdNPs to immobilize aptamers via palladium-sulfur chemistry. PdNPs can catalyze the oxidation of dopamine to produce aminochrome and its derivative, which may function as the electron acceptors of COP for the generation of an enhanced photocurrent. In the absence of cancer cells, the electrons on the conduction band of COP on the electrode transfer to the aminochrome and O2, while the electrons on the electrode transfer to the hole of valence band, resulting in a high cathodic photocurrent. In the presence of cancer cells, the trapped cancer cells efficiently cover the electrode to reduce the surface of COP/PdNPs, resulting in the decrease of catalytic precipitation on the electrode and consequently the generation of a low PEC signal. This PEC cytosensor exhibits high sensitivity with a detection limit of 8 cells mL−1 and a large dynamic range from 10 to 106 cells mL−1. Moreover, this PEC cytosensor has distinct advantages of high selectivity, good reproducibility and excellent stability, and it can be extended to directly detect various cancer cells through the integration with corresponding specific aptamers.

Recognition of M2 type tumor-associated macrophages with ultrasensitive and biocompatible photoelectrochemical cytosensor based on Ce doped SnO2/SnS2 nano heterostructure

Tumor-associated macrophages (TAMs) play central roles in the regulation of tumor growth. TAMs can be differentiated into M1 and M2 types, which are responsible for the inhibition and growth of tumor tissues, respectively. Recognition of M2-TAMs is significant for the diagnosis and therapy of cancer, which is however severely limited due to the deficiency of selective and sensitive photoelectrochemical sensors. In this work, using Ce doped SnO2/SnS2 nano heterostructure as the highly sensitive platform, a photoelectrochemical sensor enabling the recognition of M2-TAMs was fabricated for the first time. By the decoration of CD163 antibody on the platform, the ultrasensitive photoelectrochemical sensor can selectively detect the CD163 protein on the surface of M2-TAMs. To our best knowledge, this is the first demonstration for recognition of M2-TAMs using photoelectrochemical method. The fabricated cytosensor has ultra-sensitive photocurrent response, applicable biological compatibility, high selectivity and relatively wide linear sensing range (5×101 to 1×105cells/ml) with a low detection limit (50cells/ml) for the detection of M2-TAMS. This kind of PEC cytosensor would provide a novel analysis and detection strategy for M2-TAMs.

Introduction of an antifouling photoelectrode: an effective strategy for a high-performance photoelectrochemical cytosensor.

As nonspecific adsorption or biofouling has obvious side effects on the selectivity, it is a great challenge for cytosensors to detect target cells in practical biological samples. In this study, we first propose the design and synthesis of an antifouling photoelectrode. The antifouling photoelectrode not only has the desired photocurrent response, but also possesses an unexpected antifouling capability of resisting nonspecific adsorption of biomolecules. Herein, the PEDOT-HPG/SnS/ZnO-NT antifouling photoelectrode was formed and a robust photoelectrochemical cytosensor with enhanced sensitivity and selectivity has been demonstrated.

Robust photoelectrochemical cytosensor in biological media using antifouling property of zwitterionic peptide

Resulting from nonspecific adsorption or obvious biofouling, target detection in real biological media is a potential challenge for most of the biosensors. Herein, we first report an antifouling photoelectrochemical (PEC) cytosensor by using zwitterionic peptide. The typical cervical carcinoma Henrietta Lacks (HeLa) cell was chosen as a target model and the aptamer AS1411 was used as its recognition element. TiO2 nanoparticles (NPs) and ZnIn2S4 nanocrystals (NCs) were modified in order on a bare indium–tin oxide (ITO), forming ITO/TiO2/ZnIn2S4 electrode as the PEC matrix to immobilize aptamer AS1411 and zwitterionic peptide. The fabricated PEC cytosensor exhibited a high sensitivity toward HeLa cell detection, with the detection limit of 34 cells/mL. Besides, owning to excellent antifouling property of the zwitterionic peptide, evidently reduced nonspecific adsorption of the cytosensor was realized in the biological media.

Photoelectrochemical cell enhanced by ternary heterostructured photoanode: Toward high-performance self-powered cathodic cytosensing

Previously reported photoelectrochemical (PEC) cytosensing commonly relied on the use of photoelectrodes as both signaling sources and platforms to accommodate the biorecognition events. In such a design, the side reaction between photoelectrodes and potential reductive species in the biological media as well as the interplay between the photoelectrodes and biomolecules will inevitably impair the performance of the corresponding PEC cytosensors. Herein, we presented a facile and efficient PEC cytosensor by separating capture probe from the photoelectrode. The system is operated upon by using a ternary heterostructured photoanode to provide an evident and stable photocurrent signal, an aptamer-based biocathode for recognizing and capturing the target cells, and the corresponding signal reduction from the cell-induced steric hindrance effect. Exemplified by human breast cancer cells (MCF-7), the proposed system realizes the separation of the signaling photoanode and the sensing biocathode toward a sensitive and selective self-powered PEC MCF-7 cytosensor. This work reports a new PEC cytosensing protocol, and it is expected to attract more interest in the research of high-performance PEC cytosensing.

Red light-driven photoelectrochemical biosensing for ultrasensitive and scatheless assay of tumor cells based on hypotoxic AgInS2 nanoparticles

A novel red light-driven photoelectrochemical (PEC) biosensing platform based on hypotoxic ternary mercaptopropionic acid (MPA)-capped AgInS2 nanoparticles (NPs) with excellent hydrophily and biocompatibility was proposed. AgInS2 NPs as a PEC sensing substrate exhibited high photon-to-current conversion efficiency under red light excitation, generating an intensive photocurrent for enhancing the sensitivity of PEC determination. After the introduction of the amino-terminated sgc8c aptamer onto the interface of AgInS2 NPs, the overexpressed protein tyrosine kinase-7 on the surface of lymphoblast CCRF-CEM cells could be efficiently captured. Using CCRF-CEM cell as a model analyte, an ultrasensitive PEC biosensor for scatheless assay of cells at the applied potential of 0.15 V under a red light excitation of 630 nm was designed based on the significant decline of photocurrent intensity after capturing CCRF-CEM cells. The developed PEC cytosensor demonstrated an excellent cell-capture ability, as well as a wide linear range from 1.5 × 102 to 3.0 × 105 cells/mL and a low detection limit of 16 cells/mL for CCRF-CEM cells. In addition, the resulting assay method verified high selectivity and negligible cytotoxicity for cells assay. This work provided an alternative method for scatheless assay of tumor cells, which would have promising prospect in clinical diagnoses of cancer.

Conjugated Polymer-Based Photoelectrochemical Cytosensor with Turn-On Enable Signal for Sensitive Cell Detection.

In this work, a new photoelectrochemical (PEC) cytosensor was constructed by using cationic polyfluorene derivative, poly(9,9-bis(6'-(N,N,N,-trimethylammonium)hexyl)fluorene-co-alt-1,4-phenylene)bromide (PFP) as the photoelectric-responsive material for sensitive cell detection. Positive-charged PFP with high photoelectric conversion efficiency can generate robust photocurrent under light illumination. In the PEC cytosensor, 3-phosphonopropionic acid was linked to the indium tin oxide electrode, followed by modification with antiepithelial-cell-adhesion-molecule (EpCAM) antibody via amide condensation reaction. Thus, target SKBR-3 cells with overexpressed EpCAM antigen could be captured onto the electrode via the specific antibody-antigen interactions. Upon adding cationic PFP, a favorable electrostatic interaction between cationic PFP and negatively charged cell membrane led to a turn-on detection signal for target SKBR-3 cells. This new cytosensor not only exhibits good sensitivity because of the good photoelectric performance of conjugated polymers, but also offers decent selectivity to target cells by taking advantage of the specific antibody-antigen recognition.

Peptide-Based Photoelectrochemical Cytosensor Using a Hollow-TiO2/EG/ZnIn2S4 Cosensitized Structure for Ultrasensitive Detection of Early Apoptotic Cells and Drug Evaluation.

The ability to rapidly detect apoptotic cells and accurately evaluate therapeutic effects is significant in cancer research. To address this target, a biocompatible, ultrasensitive photoelectrochemical (PEC) cytosensing platform was developed based on electrochemically reduced graphene (EG)/ZnIn2S4 cosensitized TiO2 coupled with specific recognition between apoptotic cells and phosphatidylserine-binding peptide (PSBP). In this strategy, the HL-60 cells were selected as a model and C005, nilotinib, and imatinib were selected as apoptosis inducers to show cytosensing performances. In particular, a TiO2 photoactive substrate was designed as hollow spheres to enhance the PEC performance. Graphene was electrodeposited on the hollow TiO2-modified electrode to accelerate electron transfer and increase conductivity, followed by in situ growth of ZnIn2S4 nanocrystals as photosensitizers via successive ionic layer adsorption and reaction method, forming a TiO2/EG/ZnIn2S4 cosensitized structure that was used as a PEC matrix to immobilize PSBP for the recognition of early apoptotic cells. The detection of apoptotic cells was based on steric hindrance originating from apoptotic cell capture to induce an obvious decrease in the photocurrent signal. The ultrahigh sensitivity of the cytosensor resulted from enhanced PEC performance, bioactivity, and high binding affinity between PSBP and apoptotic cells. Compared with other assays, incorporate toxic elements were avoided, such as Cd, Ru, and Te, which ensured normal cell growth and are appropriate for cell analysis. The designed PEC cytosensor showed a low detection limit of apoptotic cells (as low as three cells), a wide linear range from 1 × 103 to 5 × 107 cells/mL, and an accurate evaluation of therapeutic effects. It also exhibited good specificity, reproducibility, and stability.

Photoelectrochemical Cytosensing of RAW264.7 Macrophage Cells Based on a TiO2 Nanoneedls@MoO3 Array.

We have developed a photoelectrochemical (PEC) cytosensor for ultrasensitive detection of RAW264.7 cells by the signal change of a TiO2 nanoneedles (NNs)@MoO3 array. For the first time, a TiO2 NNs@MoO3 array was adopted for the fabrication of the cytosensor for the signal output. The well-matched alignment of TiO2 NNs and MoO3 efficiently suppresses the recombination of photogenerated electron and hole (e-/h+) pairs for improved photon-to-current conversion efficiency. The RAW264.7 cell and F4/80 antibody could form the biocomplexes because of the specific recognition between each other. The constructed PEC cytosensor based on the TiO2 NNs@MoO3 array displayed good PEC property for detection of RAW264.7 cells. The numbers of RAW264.7 cells are directly detected through the decrement of photocurrent intensity, due to the increased steric hindrance when RAW264.7 cells are captured. The PEC cytosensor showed an ultrasensitive response to RAW264.7 cells with a linear range of 50-15 000 cells/mL and a detection limit of 50 cells/mL. The designed cytosensor based on a TiO2 NNs@MoO3 array offers an ideal platform to detect RAW264.7 cells with excellent stability, reproducibility, and selectivity and served as a model for the fabrication of cytosensors for other cells.

Graphene–CdS Nanocomposites: Facile One‐Step Synthesis and Enhanced Photoelectrochemical Cytosensing

Graphene-CdS (GR-CdS) nanocomposites were prepared in a one-step synthesis in aqueous solution. The synthetic approach was simple and fast, and it may be extended for the synthesis of other GR-metal-sulfide nanocomposites. The as-prepared GR-CdS nanocomposite films inherited the excellent electron-transport properties of GR. In addition, the heteronanostructure of the GR-CdS nanocomposites facilitated the spatial separation of the charge carriers, thus resulting in enhanced photocurrent intensity, which makes it a promising candidate for photoelectrochemical applications. This strategy was used for the fabrication of an advanced photoelectrochemical cytosensor, based on these GR-CdS nanocomposites, by using a layer-by-layer assembly process. This photoelectrochemical cytosensor showed a good photoelectronic effect and cell-capture ability, and had a wide linear range and low detection limit for Hela cells. The as-synthesized GR-CdS nanocomposites exhibited obviously enhanced photovoltaic properties, which could be an efficient platform for many other high-performance photovoltaic devices.

Aptamer based photoelectrochemical cytosensor with layer-by-layer assembly of CdSe semiconductor nanoparticles as photoelectrochemically active species

A label-free photoelectrochemical cytosensor for highly sensitive and specific detection of Ramos cell was developed based on photoactive films. The films were fabricated by a layer-by-layer (LBL) assembly of positively charged poly(dimethyldiallylammonium chloride) (PDDA) and negatively charged CdSe semiconductor nanoparticles (NPs) capped with mercaptoacetic acid. The resulting modified electrodes were tested as sensors for Ramos cell through the recognition of DNA aptamer which was covalently bound to the electrode using the classic coupling reactions between –COOH groups on the surfaces of CdSe NPs and –NH 2 groups of the aptamer. The newly developed cytosensor exhibited excellent sensitivity and selectivity. The linear range was from 160 to 1600 cells/mL and the detection limit was 84 cells/mL.