DESIGN OF MICROPHYSIOMETER BASED ON MULTIPARAMETER CELL-BASED BIOSENSORS FOR QUICK DRUG ANALYSIS

Cellular metabolism arouses the changes of substance in extracellular physiological microenvironment,and the metabolic level reflects the physiological state of cells.This paper developed a novel microphysiometer automatic analysis instrument based on multiparameter cell-based biosensors for quick drug analysis.This study included the multiparameter cell-based biosensors,cell culture chamber,drug auto-injection detection and analysis.The analysis instrument was capable of real-time detection for the acidic product and other chemical parameters generated by the cellular metabolism in the micro-volume.Finally,the paper employs human breast cancer cell line MCF-7 and drug experiments to verify the performance of microphysiometer,and study effects of different drugs on cell metabolism.Further,the research explores drug analysis method of the multiparameter microphysiometer.The results showed that the cell-based microphysiometer system provides a utility platform for rapid,long-term and automatic cell physiological environment detection and drug analysis.

Cell-Based Biosensors and Bio-MEMS for Its New Applications

This paper reviews a novel cell-based biosensor and Bio-MEMS which incorporate living cells as sensing elements that convert a change in immediate environment to signals conducive for processing.It is characterized with high sensitivity,excellent selectivity and fast response and have been implemented for a number of applications ranging from pharmaceutical screening to environmental pollutant detection.This paper also introduces our recent work about Light-Addressable Potentiometric Sensors (LAPS),Field Effect Transistor (FET),Micro-Electrode Array Sensors (MEAS) and Bio-MEMS for detecting the changes of concentration of extracellular ions and the action potential of living cell under effect of drugs and environmental parameters.Finely, the paper gives some prospects of cell-based biosensors in the future.

Cell-based biosensors:Towards the development of cellular monitoring

Cell-based biosensors (CBBs), a research hot-spot of biosensors, which treat living cells as sensing elements, can detect the functional information of biologically active analytes. They characterize with high sensitivity, excellent selectivity and rapid response, and have been applied in many fields, such as biomedicine, environmental monitoring and pharmaceutical screening. Recently cell-cultured technology, silicon microfabrication technology and genetic technology have promoted exploration of CBBs dramatically. To elucidate the novel research findings and applications of cell- based biosensors, this paper summarizes various research approaches, presents some challenges and proposes the research trends.

Application and prospect of semiconductor biosensors in detection of viral zoonoses

The rapid spread of viral zoonoses can cause severe consequences,including huge economic loss,public health problems or even global crisis of society.Clinical detection technology plays a very important role in the prevention and control of such zoonoses.The rapid and accurate detection of the pathogens of the diseases can directly lead to the early report and early successful control of the diseases.With the advantages of being easy to use,fast,portable,multiplexing and cost-effective,semiconductor biosensors are kinds of detection devices that play an important role in preventing epidemics,and thus have become one of the research hotspots.Here,we summarized the advances of semiconductor biosensors in viral zoonoses detection.By discussing the major principles and applications of each method for different pathogens,this review proposed the directions of designing semiconductor biosensors for clinical application and put forward perspectives in diagnostic of viral zoonoses.

Potential Power of the Pyramidal Structure VII: Effects of Pyramid Power and Bio-Entanglement on the Circadian Rhythm of Biosensors

We have demonstrated the existence of a pyramid power and have revealed its characteristics by strictly scientific experiments using biosensors. We also revealed the existence of a Bio-Entanglement, an entangled relationship between biosensors. A parallel study of biosensors (edible cucumber slices) had also been conducted, and we found that the circadian rhythm of gas concentrations emitted from biosensors changes seasonally. The pyramid power and Bio-Entanglement did not change the number of cycles in the periodic approximation curve representing circadian rhythm. Therefore, in this paper we analyzed the influence of the pyramid power and Bio-Entanglement, i.e., their influence on the phase, amplitude, and correlation coefficient of the periodic approximation curve representing the circadian rhythm of emitted gas concentrations. The main results are as follows. 1) The pyramid power shifted the phase of the periodic approximation curve representing the circadian rhythm by 43 minutes. 2) The amplitude of the periodic approximation curve changed with the pyramid power and the Bio-Entanglement. The effect on the lower and upper sections of the biosensors stacked in two layers was different, with a tendency to increase the amplitude of the lower layer and decrease the amplitude of the upper layer. 3) The pyramid power and the Bio-Entanglement affected the correlation coefficient between gas concentration and the periodic approximation curve representing the circadian rhythm of gas concentration. The effect on the lower and upper layers of the biosensors was different, with a tendency for the lower layer correlation coefficient to be larger and the upper layer correlation coefficient to be smaller. Previously we demonstrated that the pyramid power and the Bio-Entanglement affect the ratio of gas concentration, i.e., psi index Ψ. In this paper we demonstrate for the first time that the pyramid power and the Bio-Entanglement affect time, i.e., phase difference.

Biosensors for waterborne virus detection: Challenges and strategies

Waterborne viruses that can be harmful to human health pose significant challenges globally,affecting health care systems and the economy.Identifying these waterborne pathogens is essential for preventing diseases and protecting public health.However,handling complex samples such as human and wastewater can be challenging due to their dynamic and complex composition and the ultralow concentration of target analytes.This review presents a comprehensive overview of the latest breakthroughs in waterborne virus biosensors.It begins by highlighting several promising strategies that enhance the sensing performance of optical and electrochemical biosensors in human samples.These strategies include optimizing bioreceptor selection,transduction elements,signal amplification,and integrated sensing systems.Furthermore,the insights gained from biosensing waterborne viruses in human samples are applied to improve biosensing in wastewater,with a particular focus on sampling and sample pretreatment due to the dispersion characteristics of waterborne viruses in wastewater.This review suggests that implementing a comprehensive system that integrates the entire waterborne virus detection process with high-accuracy analysis could enhance virus monitoring.These findings provide valuable insights for improving the effectiveness of waterborne virus detection,which could have significant implications for public health and environmental management.

A brief review of novel nucleic acid test biosensors and their application prospects for salmonids viral diseases detection

Viral diseases represent one of the major threats for salmonids aquaculture.Early detection and identification of viral pathogens is the main prerequisite prior to undertaking effective prevention and control measures.Rapid,sensitive,efficient and portable detection method is highly essential for fish viral diseases detection.Biosensor strategies are highly prevalent and fulfill the expanding demands of on-site detection with fast response,cost-effectiveness,high sensitivity,and selectivity.With the development of material science,the nucleic acid biosensors fabricated by semiconductor have shown great potential in rapid and early detection or screening for diseases at salmonids fisheries.This paper reviews the current detection development of salmonids viral diseases.The present limitations and challenges of salmonids virus diseases surveillance and early detection are presented.Novel nucleic acid semiconductor biosensors are briefly reviewed.The perspective and potential application of biosensors in the on-site detection of salmonids diseases are discussed.

An efficient 3D cell-based discrete fracture-matrix flow model for digitally captured fracture networks

Complex hydraulic fracture networks are critical for enhancing permeability in unconventional reservoirs and mining indus-tries.However,accurately simulating the fluid flow in realistic fracture networks(compared to the statistical fracture net-works)is still challenging due to the fracture complexity and computational burden.This work proposes a simple yet efficient numerical framework for the flow simulation in fractured porous media obtained by 3D high-resolution images,aiming at both computational accuracy and efficiency.The fractured rock with complex fracture geometries is numerically constructed with a cell-based discrete fracture-matrix model(DFM)having implicit fracture apertures.The flow in the complex fractured porous media(including matrix flow,fracture flow,as well as exchange flow)is simulated with a pipe-based cell-centered finite volume method.The performance of this model is validated against analytical/numerical solutions.Then a lab-scale true triaxial hydraulically fractured shale sample is reconstructed,and the fluid flow in this realistic fracture network is simu-lated.Results suggest that the proposed method achieves a good balance between computational efficiency and accuracy.The complex fracture networks control the fluid flow process,and the opened natural fractures behave as primary fuid pathways.Heterogeneous and anisotropic features of fluid flow are well captured with the present model.

Wearable sweat biosensors on textiles for health monitoring

With the rapid technological innovation in materials engineering and device integration,a wide variety of textilebased wearable biosensors have emerged as promising platforms for personalized healthcare,exercise monitoring,and pre-diagnostics.This paper reviews the recent progress in sweat biosensors and sensing systems integrated into textiles for wearable body status monitoring.The mechanisms of biosensors that are commonly adopted for biomarkers analysis are first introduced.The classification,fabrication methods,and applications of textile conductors in different configurations and dimensions are then summarized.Afterward,innovative strategies to achieve efficient sweat collection with textile-based sensing patches are presented,followed by an in-depth discussion on nanoengineering and system integration approaches for the enhancement of sensing performance.Finally,the challenges of textile-based sweat sensing devices associated with the device reusability,washability,stability,and fabrication reproducibility are discussed from the perspective of their practical applications in wearable healthcare.

Recent progress in microbial cell surface display systems and their application on biosensors

Microbial cell surface display technology is a recombinant technology to express target proteins on the cell membrane,which can be used to redesign the cell surface with functional proteins and peptides.Bacterial and yeast surface display systems are the most common cell surface display systems of prokaryotic and eukaryotic proteins,that are widely applied as the core elements in the field of biosensors due to their advantages,including enhanced stability,high yield,good safety,expression of larger and more complex proteins.To further promote the performance of biosensors,the biomineralized microbial surface display technology was proposed.This review summarized the different microbial surface display systems and the biomineralized surface display systems,where the mechanisms of surface display and biomineralization were introduced.Then we described the recent progress of their applications on biosensors for different types of detection targets.Finally,the outlooks and tendencies were discussed and forecasted with the expectation to provide some general functions and enlightenments to this aspect of research.

A Novel Structure of LAPS Array for Cell-Based Biosensor

The light-addressable potentiometric sensor (LAPS) is a semiconductor-based cellular biosensor with an electrolyte-insulator-semiconductor (EIS) structure.By depositing biocompatible layers on the sensing surface for cell culture, it can be used to detect bioelectrical parameters of cells.The characteristic curve for photocurrent versus applied bias voltage to the system shows a current-voltage curve (Ⅰ-Ⅴcurve).This technique can be used to detect the action potential changes towards different drugs based on the bias voltage dependence of an optical current,and provides a dynamic system by scanning light beam at the very cell on the sensor device.The LAPS overcomes the limitation of recording sites,but high spatial resolution and sensitivity are also paramount.This paper discussed a novel structure of LAPS array for extracellular monitoring to decrease potential noise level.Both characteristics of active recording array areas and cell culture conditions are measured.

Cell-based therapies for limbal stem cell deficiency: a literature review

Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue.Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants.In this review,we describe the success rates,and complications of different cell-based therapies for LSCD.We also discuss each therapy’s relative strengths and weaknesses,their history in animal and human studies,and their effectiveness compared to traditional transplants.Methods:PubMed was searched for publications using the terms LSCD,cell-based therapy,cultivated limbal epithelial transplantation(CLET),cultivated oral mucosal epithelial transplantation(COMET),and mesenchymal stem cells from 1989 to August 2022.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.Key Content and Findings:current cell-based therapies for LSCD are CLET and non-limbal epithelial cells.Non-limbal epithelial cell methods include COMET,conjunctival epithelial autografts,and mesenchymal stem/stromal cells(MSCs).Moreover,several alternative potential sources of non-limbal cells have described,including induced pluripotent stem cells(iPSCs),human embryonic stem cells(hESCs),human dental pulp stem cells,hair follicle bulge-derived epithelial stem cells,amniotic membrane epithelial cells,and human umbilical cord lining epithelial cells.Conclusions:Cell-based therapies are a promising treatment modality for LSCD.While CLET is currently the only approved cell-based therapy and is only approved in the European Union,more novel methods have also been shown to be effective in human or animal studies thus far.Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure.iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated.Lastly,cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study.Several potential sources of non-limbal cells are under investigation.

Novel Sustainable Cellulose Acetate Based Biosensor for Glucose Detection

In this study,green zinc oxide(ZnO)/polypyrrole(Ppy)/cellulose acetate(CA)film has been synthesized via solvent casting.This film was used as supporting material for glucose oxidase(GOx)to sensitize a glucose biosensor.ZnO nanoparticles have been prepared via the green route using olive leaves extract as a reductant.ZnO/Ppy nanocomposite has been synthesized by a simple in-situ chemical oxidative polymerization of pyrrole(Py)monomer using ferric chloride(FeCl3)as an oxidizing agent.The produced materials and the composite films were characterized using X-ray diffraction analysis(XRD),scanning electron microscope(SEM),Fourier transform infrared(FTIR)and thermogravimetric analysis(TGA).Glucose oxidase was successfully immobilized on the surface of the prepared film and then ZnO/Ppy/CA/GOx composite was sputtered with platinum electrode for the current determination at different initial concentrations of glucose.Current measurements proved the suitability and the high sensitivity of the constructed biosensor for the detection of glucose levels in different samples.The performance of the prepared biosensor has been assessed by measuring and comparing glucose concentrations up to 800 ppm.The results affirmed the reliability of the developed biosensor towards real samples which suggests the wide-scale application of the proposed biosensor.

含裂纹压电材料的Cell-Based光滑有限元法

裂纹缺陷限制了压电材料更广泛的应用和相关器件性能的进一步提升.为提高求解压电材料断裂参数的精度和效率,将复势函数法和Cell-based光滑有限元法引入到含裂纹平面压电材料问题中,提出了含裂纹压电材料的Cell-based光滑有限元法.以含中心裂纹压电平板的问题为例,对不同材料、裂纹长度、网格和光滑子元数下的正则强度因子进行了讨论,并与FEM作了对比,数值算例结果表明,Cell-based光滑有限元法改善了有限元法刚度"偏硬"的缺点,具有高精度、高效率的优点.

基于随机场正交展开理论的Cell-based随机光滑有限元方法

为解决工程结构中随机参数大变异问题,提出基于正交展开理论的Cell-based随机光滑有限元方法.该方法采用Karhunen-Loève级数将随机场分解为不相关随机变量,再使用混沌多项式将位移随机响应展开,将展开后的随机场及位移响应引入到Cell-based光滑有限元中.详细推导了基于正交展开理论的Cell-based随机光滑有限元平衡方程,进一步给出了结构位移均值与协方差矩阵的计算公式,具有对网格要求低、计算精度高的优点,并对材料特性具有随机性的带孔方板的随机响应问题进行了分析,数值算例结果表明该方法是正确有效的.

复合材料层合板的摄动随机Cell-Based光滑有限元

随机性是实际工程结构的固有特性,如何更真实地描述含随机参数结构的随机响应及统计特性,对工程结构的可靠性设计具有非常重要的意义。本文基于Cell-Based光滑有限元,采用四边形单元,推导了基于一阶剪切变形理论的复合材料层合板的光滑有限元公式,降低了网格划分要求,适应不规则网格,并采用离散剪切间隙有效地消除了剪切自锁;结合摄动法和随机场理论,导出了复合材料层合板的摄动随机光滑有限元平衡方程,并给出了结构随机响应数字特征的计算公式,求解了材料属性含随机性的复合材料层合板的随机响应问题,数值算例结果表明了本方法的有效性和准确性。

Biosensors for hepatitis B virus detection

A biosensor is an analytical device used for the detection of analytes,which combines a biological component with a physicochemical detector.Recently,an increasing number of biosensors have been used in clinical research,for example,the blood glucose biosensor.This review focuses on the current state of biosensor research with respect to efficient,specific and rapid detection of hepatitis B virus(HBV).The biosensors developed based on different techniques,including optical methods(e.g.,surface plasmon resonance),acoustic wave technologies(e.g.,quartz crystal microbalance),electrochemistry(amperometry,voltammetry and impedance) and novel nanotechnology,are also discussed.

Current Technologies of Synthetic Biosensors for Disease Detection:Design,Classification and Future Perspectives

Synthetic biology aims to endow living cells with new functions by incorporating functional gene networks into them.By overexpressing,blocking and rewiring native gene pathways,synthetic biologists have harnessed this promising technology to reprogram cells to perform diverse tasks such as drug discovery,biopharmaceutical manufacturing,gene therapy and tissue engineering,etc.In this review,we focus on current technologies of synthetic biosensors for disease detection.We start with the design principle of synthetic biosensors.Then we move towards the characteristics of simple synthetic biosensors,which can respond to a single input signal,and complex synthetic biosensors including Boolean gate biosensors,cascade biosensors,time-delay biosensors,oscillator biosensors and hysteretic biosensors,which can respond to more than two input signals and perform complex tasks.Synthetic biosensor has showed great potential in disease detection,but it is still in its infancy stage.More efforts should be made in identifying and constructing clinically relevant regulation systems.Computational tools are also needed in the design process in order to guarantee the precision of the synthetic biosensor.The ultimate goal of a synthetic biosensor is to act as a therapeutic sensor-effector device that connects diagnostic input with therapeutic output and therefore provides all-in-one diagnostic and therapeutic solutions for future gene-and cell-based therapies.

Study on the Therapeutic Mechanism of the Active Principle of the Chinese Drug Paeoniae Radix 801 through Affinity Biosensors IAsys Plus Quartz Crystal Microbalance

Objective: To study the targeted point and mechanism of the function of the blood-activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its cardiovascular protective effects and its specific binding with endothelin 1(ET-1) as well as the dynamics of the two's interactive function by means of using affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM). Methods: ET-1 was immobilized on the surfaces of IAQCM by using the new surface modification methods. The PR801 in the solution was detected by modified substrates and the specific binding between PR801 and ET-1 was studied. Results: The curves went up or down after adding PR801.There is specific binding between PR801 and ET-1. The bound mass were 0.458 ng/mm 2 and 133.54 ng/cm 2, respectively. There exists relatively good stability with these two methods. Conclusion: The affinity biosensors: IAQCM can be used to study the interaction mechanism between PR801 and ET-1, providing a new way to study the interaction mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore, ET-1 is another target that PR801 can bind specifically besides thromboxane A 2.

Application and Development of Biosensors

As a new kind of analytical instrument, the principles, types and characters of biosensors were discussed in this paper. A biosensor is usually composed of a recognition element of biological origin and a physicochemical transducer. The biological element is capable of sensing the presence, activity or concentration of a chemical analyse in solution. The sensing takes place either as a binding event or a biocatalytical event. These interactions produce a measurable change in a solution property, in which the transducer is converted into a quantifiable electrical signal. The principles, types and applications of biosensors in environmental inspection, food production, clinical medicine and military defense were reviewed, and the trends in research were predicated, Furthermore, an attempt had been made to describe the future development directions and prospects.