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preface
With the growing demand for accurate detection of biomolecules at low or even trace concentrations, the research and application of biosensors has become an important way to solve this challenge.
Biosensors use specific interactions between biometric elements and target small molecules, have a high degree of sensitivity, and are more precise and specific than traditional physicochemical sensors.
By introducing nanomaterials modified with polymers and biometric elements, the performance of biosensors is further enhanced, including sensitivity, specificity, stability, and immunity to interference.
Our main focus is on the research progress of nano-biosensors based on precious metals and semiconductor materials.
Precious metal nanoparticles
Gold nanoparticles (AuNPs) have good biocompatibility, rich surface modification properties and unique optical properties, which are related to the surfactants, shape, size and structure of the nanoparticles.
Covalent modification is usually performed by sodium borohydride reduction and ligand substitution. The surface of the nanoparticles can be easily chemically modified with ligands containing functional groups, such as mercaptans, phosphine, and amines.
For example, the reduction of chloroauric acid in ethanol solutions with sillymthiol as a protective agent or the encapsulation of gold nanoparticles with thiopolyethylene glycol may be useful for applications in various fields of nucleic acids, proteins, and immunoassays.
The high surface free energy of gold nanoparticles allows them to adsorb surrounding molecules through non-covalent interactions, reducing the surface free energy of surface ligand functional groups, thus allowing some other parts to attach, such as proteins, nucleic acids, and antibodies, to improve their properties.
Depending on their properties, they can be used in various biomedical fields such as medical testing, imaging and therapy, photochemotherapy, photodynamic therapy, and photothermal therapy.
In the study, human epidermal growth factor receptor 2 was immobilized on the surface of the screen-printed electrode by electrostatic adsorption and modified with gold nanoparticles (~20 nm diameter) to support aptamer immobilization.
A response is received with only a binding time of 5 minutes and a loglinear response is displayed over a wide concentration range.
Gold nanoparticles with surface plasmon resonance (SPR) phenomena are used in nucleic acid construction and protein detection and analysis.
SPR refers to the resonance phenomenon that may occur when the total reflection phenomenon occurs on the surface of the prism and the metal film, and the light forms extinction waves into the light-sparse medium, and under the premise of conservation of energy, there is a certain plasma wave in the medium when the two waves meet.
They can convert biometric reflections into optical or electrical signals, so they bind to DNA, RNA, and amino acids, making them highly effective in the detection of nucleic acids and proteins.
In addition, the test has many advantages, such as simple operation, good oxidation resistance and biocompatibility. Given that plasma coupling of surfaces between particles leads to a shortening of the distance between AuNPs, and significant color changes in different aggregation states, many colorimetric sensors have been developed.
In a recent study, a random DNA double walker method for ultrafast colorimetric bacterial detection was proposed. This method has ultrafast reaction kinetics and color-changing mechanism, linear response range of 15-100 CFU/mL, detection limit of 105 CFU/mL, so it can detect bacteria sensitively and specifically within 1 min.
The sensitivity of SPR biosensors is proportional to the overlapping integral of the modal electromagnetic field with the environmental medium [35]. Therefore, proper surface treatment is worth it in terms of improving the performance of these sensors.
In high refractive index, dielectric thin film materials play an important role in improving the sensitivity, resolution, and specificity of biosensors in detection.
A bionanonetwork was developed by pyridineporphyrin-mediated calcium-sophene functionalized AuNPs composites (Apt/PyP-pSC4-AuNPs) as an SPR signal amplification tag for sensitive and rapid brain natriuretic peptide (BNP) assay as a quantitative plasma biomarker to detect the presence and severity of heart failure.
Wide linear concentration range (1–10,000 pg/mL (R2 = 0.9852)) and lower detection limit (0.3 pg/mL). However, increased sensitivity of biosensors can lead to a lack of reliability due to contamination of spectral signals or the fragility of other analytes.
So the researchers tried to solve this problem with other optical phenomena. Surface enhanced Raman scattering (SERS) is a phenomenon in which the electromagnetic field is enhanced when molecules are adsorbed on the metal surface and the Raman signal of adsorbed molecules is enhanced, which can be used to make the biological detection process more sensitive and easy.
Recently, we proposed a novel SPR/SERS dual-mode plasma biosensor based on a network of catalytic hairpin assembly (CHA)-induced AuNPs, aiming for high sensitivity and reliable detection of cancer-associated miRNA-652.
The proposed biosensor consists of AuNP (probe 1), H1 and 4-mercaptobenzoic acid (4-MBA) co-modified AuNP and 6-carboxy-rhodamine (ROX)-labeled H2 (fuel chain) that captures DNA functionalization.
Then, the CHA reaction triggered by the target forms a network consisting of probe 1-probe 2, resulting in color changes in darkfield microscopy (DFM) images and enhanced SERS effects.
In addition, the SPR sensing mode can be achieved by extracting the integral optical density of the darkfield color in the DFM image.
At present, gold nanomaterial modified biosensors have been widely used in bioanalysis, environmental monitoring, medical diagnosis and other fields, and we show some examples of AuNPs applications.
We need to constantly strive to explore and optimize this technology to solve various problems encountered in practical applications. First, gold nanoparticle preparation methods are usually small-batch or laboratory-grade, so larger scale preparation methods need to be explored.
This is critical for translating AuNPs biosensor technology into practical clinical applications. Secondly, the sensitivity, specificity, and response speed of AuNPs biosensors need to be further optimized to meet more stringent and complex biomedical detection requirements.
Finally, gold nanomaterials themselves may have toxic effects on humans, so when using AuNPs biosensors, their biocompatibility and related safety studies should be comprehensively and deeply evaluated.
Silver nanoparticles (NPs) are currently popular metal nanomaterials with a wide range of applications in the biomedical field, including diagnostics, imaging, and drug delivery.
AgNPs are usually synthesized by reducing silver salts and adding polyvinylpyrrolidone (PVP) or citrate to improve the stability of AgNPs, thereby benefiting their application in biosensors.
AgNPs have large specific surface area, good catalytic activity and high electrical conductivity. In addition, AgNPs have the optical properties of surface plasmon resonance (SPR), which contributes to Raman signal enhancement.
The SPR of AgNPs can generate electromagnetic field enhancement, which facilitates the detection of biosensors through the phenomenon of surface enhanced Raman scanning (SERS).
Biosensors using AgNP are commonly used to detect glucose, cholesterol, dopamine, DNA, and other substances by fluorescence, colorimetry, electrochemistry, and Raman spectroscopy.
Glucose testing is usually done by oxidizing glucose to gluconic acid and hydrogen peroxide (H2 or 2), followed by detecting the resulting H2 or 2 or pH changes caused by gluconic acid.
We also synthesized silica and silver (SiO2-Ag) colloidal nanoparticles to detect glucose. During detection, the sample solution and SiO2 mix and excite the -Ag colloidal nanoparticles at 260 nm, and the fluorescence spectra at 325 nm are recorded.
When excitation of SiO, 2-Ag colloidal nanoparticles release fluorescence, part of the energy is absorbed by biomolecules, and then the fluorescence intensity released is reduced.
Therefore, they can obtain glucose concentration by reducing the fluorescence intensity. This biosensor can efficiently detect glucose in human urine and serum and eliminate interference from other biomolecules, which can meet clinical needs.
In addition to this direct detection method using SiO, 2-Ag colloidal nanoparticles, methods for indirect detection of glucose have been developed. Wu et al. successfully built a colorimetric biosensor to detect glucose in the blood.
They deposited AgNPs on the surface of MIL-101 (Fe) to form peroxidase mimics. During the assay, glucose is oxidized to H2 or 2 with glucose oxidase (GOx).
They then used AgNPs@MIL-101 (Fe) and H2 or 2 to oxidize the colorless substance 3,3′,5,5′-tetramethylbenzidine (TMB), turning it into the blue product oxTMB.
Finally, the glucose concentration was calculated by detecting the absorbance change of the product by UV-Vis spectroscopy. The biosensor has a detection limit of 0.23 μM and satisfactory sensitivity in detecting glucose.
Compared to direct detection methods, indirect detection methods can detect glucose more sensitively and can reduce interference from other substances.
But the biological enzymes used are heavily influenced by the environment, which could be a new area for researchers to explore.
Most biosensors for cholesterol detection are used in combination with cholesterol oxidase (ChOx).
ChOx can break down cholesterol into H2 or 2, and then the concentration of cholesterol can be obtained by detecting the concentration of H2 or 2.Wu et al. used AgNPs@MIL-101 (Fe) as a peroxidase and substrate for SERS.
They first oxidized cholesterol to H2 or 2 with ChOx, then at H2 or 2 and AgNPs@MIL-101 (iron). Finally, they obtained cholesterol concentrations from the enhanced Raman signaling.
The AgNPs@MIL-101(Fe)-based SERS biosensor has a detection limit of 0.36 μM and enables ultra-sensitive detection of cholesterol.
Dopamine is a well-known neurotransmitter. Low levels of dopamine in the human body may lead to diseases such as Alzheimer's disease and depression, while high concentrations of dopamine may also lead to problems such as high blood pressure and nervous overexcitability.
Therefore, accurate and non-toxic detection of dopamine is an important research direction. A sensitive biosensor has been reported to detect dopamine in human urine.
They synthesized functionalized multi-walled carbon nanotubes (f-MWCNT) and AgNPs as biosensing materials modified on glass-carbon electrodes to detect dopamine concentrations based on differential pulsed voltammetry (DPV).
The biosensor has good stability and high sensitivity, with a minimum detection limit of 0.28 mM, which is much lower than the normal dopamine concentration in human urine, and can be used for routine detection.
DNA testing has recently become a very popular research direction. During gene expression, DNA is transcribed and translated into proteins with different functions and shapes.
The process of gene control traits is mainly divided into two ways: one is to control the shape of proteins, and the other is to control metabolic processes through synthetase.
So we can study the process of certain diseases by detecting DNA, which helps the process of prevention and effective treatment. Biosensors use the SERS phenomenon to detect DNA, based on the fact that different Raman peaks on the Raman spectrum represent different kinds of DNA.
AgNPs/SiNPs biosensors not only have good stability and reproducibility, but also have ultra-sensitive detection capabilities for DNA, meeting the detection limit of 1.52 pg/L.
As far as the current research is concerned, biosensors using AgNPs are often used for the detection of daily indicators, glucose detection, cholesterol detection, most of which can reduce the otherwise expensive detection cost.
In addition, other studies dedicated to detecting some early signs of serious disease have greatly aided the diagnosis due to the sensitivity of detecting abnormal indicators.
conclusion
Although the new electrochemical biosensor has improved various parameters such as linear detection range, detection limit, and stability, there are still many problems and challenges.
The biocompatibility and stability of precious metals and semiconductor nanomaterials need to be improved, for example, MOFs-based drug delivery systems are still potentially toxic in clinical applications.
The research is still in the laboratory, and the actual promotion of the user side has not yet been carried out. In addition, the development of biosensor technology requires the close cooperation of many researchers, and continuous innovation and mutual progress through mutual communication.