Liquid Crystal Biosensor Research Articles

Analytical Insights into Methods for Measuring Ischemia-Modified Albumin.

Ischemia-modified albumin (IMA) has emerged as a pivotal biomarker for the early detection of ischemic conditions, particularly myocardial ischemia, where timely diagnosis is crucial for effective intervention. This review provides an overview of the analytical methods for assessment of IMA, including Albumin Cobalt Binding (ACB), Albumin Copper Binding (ACuB), Enzyme-Linked Immunosorbent Assay (ELISA), new techniques such as liquid crystal biosensors (LCB), quantum dot coupled X-ray fluorescence spectroscopy (Q-XRF), mass spectrometry (MS), and electron paramagnetic resonance (EPR) spectroscopy. Each method was thoroughly examined for its analytical performance in terms of sensitivity, specificity, and feasibility. The ACB assay is the most readily implementable method in clinical laboratories for its cost-effectiveness and operational simplicity. On the other hand, the ACuB assay exhibits enhanced sensitivity and specificity, driven by the superior binding affinity of copper to IMA. Furthermore, nanoparticle-enhanced immunoassays and liquid crystal biosensors, while more resource-intensive, significantly improve the analytical sensitivity and specificity of IMA detection, enabling earlier and more accurate identification of ischemic events. Additionally, different biological matrices, such as serum, saliva, and urine, were reviewed to identify the most suitable for accurate measurements in clinical application. Although serum was considered the gold standard, non-invasive matrices such as saliva and urine are becoming increasingly feasible due to advances in technology. This review underscores the role of IMA in clinical diagnostics and suggests how advanced analytical techniques have the potential to significantly enhance patient outcomes in ischemic disease management.

Real-Time pH Sensor in Bacterial Microenvironments Using Liquid Crystal Core-Shell Microspheres.

It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.

Membrane Proteins in Action Monitored by pH-Responsive Liquid Crystal Biosensors.

Liquid crystal (LC) biosensors have received significant attention for their potential applications for point-of-care devices due to their sensitivity, low cost, and easy read-out. They have been employed to detect a wide range of important biological molecules. However, detecting the function of membrane proteins has been extremely challenging due to the difficulty of integrating membrane proteins, lipid membranes, and LCs into one system. In this study, we addressed this challenge by monitoring the proton-pumping function of bacteriorhodopsin (bR) using a pH-sensitive LC thin film biosensor. To achieve this, we deposited purple membranes (PMs) containing a 2D crystal form of bRs onto an LC-aqueous interface. Under light, the PM patches changed the local pH at the LC-aqueous interface, causing a color change in the LC thin film that is observable through a polarizing microscope with crossed polarizers. These findings open up new opportunities to study the biofunctions of membrane proteins and their induced local environmental changes in a solution using LC biosensors.

Cascade Structured Plasmonic Liquid Crystal Biosensor for the Rapid Detection of Harmful Bacteria Dispersed in Potable Water

AbstractPathogenic microorganisms contaminating potable water are a serious water quality concern because they have severe consequences for human and environmental health. Managing water contamination requires the availability of fast and highly sensitive point‐of‐use detection systems responsive to a wide concentration range. In the present work, this goal is achieved by realizing a cascade‐structured biosensor that exploits innovative stimuli‐responsive materials such as gold nanorods (AuNRs) and photosensitive nematic liquid crystals (NLCs). The cascade structure is fabricated by interfacing a glass substrate in a back‐to‐front arrangement, hosting an array of bioactivated AuNRs and an NLC cell. The AuNRs array integrates microfluidic channels, allowing direct water sampling and the analysis of reduced water volumes with high sensitivity. The biosensor combines in the same device two independent optical transducers: a bioactive AuNRs array (plasmonic biosensor), sensitive to refractive index alterations, and an NLC cell that detects the presence of pathogens by responding to light intensity variations. The plasmonic biosensor performs exceptionally well for very low concentrations of bacteria. In contrast, the NLC biosensor works for high‐concentration bacteria, thus providing a cascade‐like detection system able to detect bacteria in a wide concentration range from 10 to 109 CFU mL−1.

Construction of a Liquid Crystal Biosensor and Detection of Heavy Metal Ions and Organic Phosphate

Since the discovery of liquid crystal molecules have been widely used in electronic display devices. At the same time, as special “sensitive elements”, liquid crystal molecules have also been introduced into the field of sensors in recent years, especially in life science research, where they have been used to for constructing liquid crystal biosensors, the first appearance. Liquid crystal biosensors are fast, simple and low-cost, label-free, highly sensitive, and with low detection limits. Therefore, the development of new liquid crystal sensors is undoubtedly a great development in the field of chemical biosensors.

Liquid crystal assisted optical DNA biosensor for the selective detection of bacterium Neisseria gonorrhoeae

ABSTRACT A highly selective and sensitive label-free liquid crystal (LC)-based optical DNA biosensor has been reported for the detection of bacterial disease. A sensing platform is constructed using nematic LC (4-cyano-4’−pentyl biphenyl) filled in a confined mesh area of transmission electron microscope (TEM) grid placed within a Polydimethylsiloxane (PDMS) well of a fixed dimension for the detection of bacterial infection caused by Neisseria gonorrhoeae. The optical response associated with LC orientation was investigated by using N. gonorrhoeae nucleotide-specific oligonucleotide probe interacting with both the synthetic complementary ssDNA as well as genomic DNA isolated from N. gonorrhoeae under polarised optical microscope. The grey scale area of the resultant POM images was quantised using Image J software and monitored as a function of DNA concentration. The LC-cell has been able to detect the genomic DNA of N. gonorrhoeae bacteria down to the lowest detectable concentration of 10 pM. The optical response studies of LC-biosensor with genomic DNAs isolated from different bacteria showed high specificity and selectivity exclusively for N. gonorrhoeae pathogen and its potential as a convenient, rapid, and reliable label-free detection for gonorrhoea disease.

Optical Biosensing of Polarized Light

Interactions between liquid crystal molecules and target analytes open up various biosensing applications for quick screening and point-of-care applications. In this review, we categorized biosensors by type, depending on the liquid crystal mesophase, and considered several applications for the detection of biomolecules, point-of-care diagnostics and environmental monitoring. We also discuss interactions between polarized light and target pathogens dispersed in biological fluids, which result in the change of the polarization state. An array of the Stokes parameters can be compared with the pattern, and a proper pathogen can be manifested. We suggest that a combination of a micropolarizer array and a complementary metal oxide semiconductor sensor is an optimal setup for the detection of pathogens. Herein, we discuss the working principles of liquid crystal biosensors and their fabrication principles. In addition, relevant theoretical and practical issues related to liquid crystal biosensors are outlined. In general, this review gives an in-depth survey of the research on liquid crystal-based sensors, making it easier for researchers to locate their niche and make contributions to this subject from multiple viewpoints.

Computational Analysis on the Performance of Elongated Liquid Crystal Biosensors.

Elongated ellipsoidal liquid crystal microdroplet reorientation dynamics are discussed in this paper for biosensor applications. To investigate the effect of elongated droplets on nematic liquid crystal droplet biosensors, we simulated a model of a liquid crystal droplet using ellipse geometry. Director reorientation is examined in relation to the elongated droplet shape. In addition, we examined aspect ratio as a factor affecting biosensor response time in relation to surface viscosity and anchoring energy. Finally, the findings suggest that the aspect ratio should be taken into account when designing biosensors. These results can be used to develop more effective biosensors for a variety of applications. This model then predicts the director reorientation angle, which is dependent on the anchoring energy and surface viscosity. This model further suggests that both surface viscosity and homeotropic anchoring energy play an important role when it comes to the director reorientation angle. We developed and applied a nonlinear unsteady-state mathematical model utilizing torque balance and Frank free energy according to the Leslie-Ericksen continuum theory for simulating elongated nematic liquid crystal biosensor droplets with aqueous interfaces. Using the Euler-Lagrange equation, a transient liquid crystal-aqueous interface realignment is modeled by changing the easy axis when surfactant molecules are added to the interface. The realignment at the surface of the droplet is assumed to be driven by the effect of the surfactant, which causes an anchoring transition. According to the results, the response time of the biosensor depends on the aspect ratio. Therefore, the elongation has the potential to control biosensing response time. The result of our study provides a better understanding of director reorientation in elongated liquid crystal droplets in biosensing applications through the numerical results which are presented in this paper.

Liquid crystal biosensor based on AuNPs signal amplification for detection of human chorionic gonadotropin

The detection of human chorionic gonadotropin (HCG) allows for the determination of pregnancy and is thus crucial during early pregnancy testing. This study introduces a novel liquid crystal (LC) biosensor that employs Au nanoparticles (AuNPs) for signal amplification, thus enabling the detection of the HCG antigen in a micro, efficient, and cost-effective manner. The sensor design capitalizes on the unique properties of LC to facilitate the detection of HCG. In this research, the surface of the base substrate was first modified with material from DMOAP and APTES, and EDC/sulfo-NHS was used to couple AuNPs and β-hCG to form an AuNP-β-hCG conjugate that improves the coupling rate. The carboxyl group of the antibody was reacted with the aldehyde group of glutaraldehyde, which helps to fix the β-hCG antibody to the surface of the substrate. The HCG sample is immobilized on the surface of the substrate via antigen-antibody immunobinding. As signal amplifiers, the AuNPs can have a significant effect on the topology of the interface and the vertical order of the LC molecules, thus reducing the limit of detection. Finally, the limit of detection was calculated using the SPSS system, and the relationship between grey values and concentrations was also obtained. The detection limit for HCG can be as low as 1.916 × 10−3 mIU·mL−1 under ideal conditions. Compared to other detection methods for HCG, this structure provides a detection pathway with excellent sensitivity, low detection limits, and better specificity, thus offering a new idea for HCG or any other target requiring trace detection.

A Numerical Study on the Performance of Liquid Crystal Biosensor Microdroplets

The numerical results from the modeling of liquid crystals dispersed in aqueous solutions in the form of axially symmetric droplets, with the aim of helping to facilitate the development of liquid crystal biosensors, were obtained. We developed a transient two-dimensional nonlinear model obtained via torque balance that incorporates Frank’s elastic free energy. In order to perform parametric studies, we defined the scaled parameters based on the surface viscosity and the homeotropic anchoring energy at the droplet interface. To evaluate the performance of the biosensor, the average angle and characteristic time were defined as performance criteria. Using these results, we studied the bulk reorientation of liquid crystal droplets in aqueous solutions caused by biomolecular interaction. Furthermore, we examined how surface viscosity affects the performance of a biosensor in the case of weak planar anchoring. The droplet interface ordering was modeled using the Euler–Lagrange equation. The droplets’ equilibrium was determined by minimizing their total distortion energy based on the interaction between their surface and bulk elastic energy. Two factors that contributed to the biosensor performance were homeotropic strength and surface viscosity. This highlights the importance of controlling the surface and physicochemical properties to achieve the desired liquid crystal orientation. In addition, our results provide insight into the role that surface viscosity plays in controlling radial configuration.

Liquid crystal-assisted optical biosensor for early-stage diagnosis of mammary glands using HER-2

Breast cancer (BC) is one of the most commonly diagnosed cancers and the second leading cause of cancer mortality among women around the world. The purpose of this study is to present a non-labeled liquid crystal (LC) biosensor, based on the inherent feature of nematic LCs, for the evaluation of BC using the human epidermal growth factor receptor-2 (HER-2) biomarker. The mechanism of this sensing is supported by surface modification with dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) encouraging the long alkyl chains that induce a homeotropic orientation of the LC molecules at the interface. To enhance the binding efficacy of more HER-2 antibody (Ab) on LC aligning agents, a simple ultraviolet radiation-assisted method was also used to increase functional groups on the DMOAP coated slides, thereby improving binding affinity and efficiency onto HER-2 Abs. The designed biosensor makes use of the specific binding of HER-2 protein to HER-2 Ab and disruption of the orientation of LCs. This orientation change leads to a transition of the optical appearance from dark to birefringent, enabling the detection of HER-2. This novel biosensor exhibits a linear optical response to HER-2 concentration in the wide dynamic range of 10–6–102 ng/mL, with an ultra-low detection limit of 1 fg/mL. As a proof of concept, the designed LC biosensor was successfully investigated for the quantification of HER-2 protein in patients suffering from BC. Owing to the sensitivity, selectivity, and label-free detection, this biosensor may amplify the application of LC-based biosensors for the detection of most types of cancers.

Optical and dielectric realisation of biomolecular detection using gold nanoparticles bio-conjugate with liquid crystal

Dielectric biosensor based on nematic liquid crystal platform has been fabricated using sandwich immunoassay technique for the detection of a biomolecule, human cardiac troponin I (cTnI). The optical response of Liquid crystal (LC) biosensor and its corresponding frequency-dependent dielectric properties have been investigated as a function of cTnI concentration. Gold nanoparticles conjugate with detection antibody (AB-GNP) is used for the enhancement of both the optical and dielectric signal of the biosensor. AB-GNP binding with cTnI alter the surface energy of the substrate causing disturbances in LC alignment resulting in a change in transmission. The transmission of the LC cell has been found to be varying from dark to bright texture under polarized microscope as a function of cTnI concentration. A change in low-frequency permittivity with increasing cTnI concentration that forms an increasing order of sandwich immunocomplex with AB-GNP revealed an interfacial surface phenomenon. A positive shift in the onset frequency of permittivity is observed due accumulation of immunocomplex with increasing concentration of cTnI at electrode/LC interface. The dielectric response ε′ of the biosensor is fitted with Hill-Langmuir equation over a concentration range of 0.01 to 10 ng mL−1 cTnI. The dissociation constant ‘Kd’ of 1.02 ± 0.24 ng/mL−1 indicates strong cTnI binding affinity for substrate antibody. A nearby value of 1, calculated for Hill coefficient ‘n’ revealed no co-operativity characteristic of cTnI binding to the primary capture antibody, wherein each binding site of the antibody functions independently at the electrode surface, causing accumulation of charged species revealing LC interfacial surface electrical property.

Cholesteric liquid crystal biosensor platform with image analysis for rapid detection of COVID-19.

Rapid and low-cost diagnosis of coronavirus disease 2019 (COVID-19) is essential to identify infected subjects, particularly asymptomatic cases, primarily to arrest the spread of the disease through local transmission. Antibody-based chromatographic serological tests, as an alternative to the RT-PCR technique, offer only limited help due to high false positives. We propose to exploit our cholesteric liquid crystal biosensor platform for one-step, wash-free, rapid detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus directly with minimal sample pre-processing. As mentioned above, cholesteric liquid crystals are an effective and innovative approach to healthcare as a rapid test for the diagnosis of COVID-19 and other diseases.

Construction of a liquid crystal biosensor based on Fe3O4 nano-signal amplification and its application in HCG detection.

In this research, to improve the ability of nanomaterials to interfere with liquid crystal orientation, we constructed a novel liquid crystal biosensor using Fe3O4 nanospheres as signal amplifiers, which was used for the highly selective and sensitive detection of human chorionic gonadotropin (HCG). The Fe3O4 nanospheres in liquid crystal biosensors are still rare, in particular for the detection of the HCG antigen, a marker of pregnancy in women. This strategy takes advantage of the large spatial structure of Fe3O4 nanospheres to pre-immobilise β-hCG antibodies on the glass substrate, and, in the presence of HCG antigens, the antigen-antibody formed a specific immune response to disrupt the orientation of the liquid crystal. This allows an amplified optical signal to be generated for the ultimate successful detection of HCG antigen, and can greatly reduce the detectability of the target antigen concentration, ultimately greatly increasing the sensitivity of detection to a large degree. Thus, under optimal detection conditions, the minimum detection limit can be as low as 0.438 mIU mL-1. The prepared LC biosensor demonstrates excellent specificity and sensitivity compared to conventional nanomaterials used in liquid crystal biosensors, and will be of great benefit for future applications requiring trace detection of proteins, antibiotics, bacteria and so on, which is expected to provide a sensitive detection platform for HCG and other molecular monitors.

Computational Analysis to Optimize the Performance of Thin Film Liquid Crystal Biosensors

A nonlinear unsteady-state mathematical model employing torque balance and Frank free energy according to the Leslie-Ericksen continuum theory is developed and implemented to simulate the performance of nematic liquid crystal biosensor films with aqueous interfaces. A transient liquid crystal-aqueous interface realignment is modeled using the Euler–Lagrange equation by changing the easy axis when the surfactant molecules at the interface are introduced. In our study, we evaluated the dynamics between bulk and interface by controlling surface properties of the interface, such as homeotropic anchoring energy and surface viscosity. In addition, transient optical interference and response time have been examined in this study. Our parametric study results indicated that both homeotropic anchoring energy and surface viscosity at the interface contribute to bulk reorientation. Furthermore, the obtained numerical results indicate that as homeotropic anchoring strength increases, the effective birefringence decreases more gradual due to the increasing surfactant concentration at the aqueous interface, consistent with available experimental observations. Our results have been validated and compared to experimental results from thin-film liquid crystal biosensors in this study.

Liquid Crystal Droplet-Based Biosensors: Promising for Point-of-Care Testing.

The development of biosensing platforms has been impressively accelerated by advancements in liquid crystal (LC) technology. High response rate, easy operation, and good stability of the LC droplet-based biosensors are all benefits of the long-range order of LC molecules. Bioprobes emerged when LC droplets were combined with biotechnology, and these bioprobes are used extensively for disease diagnosis, food safety, and environmental monitoring. The LC droplet biosensors have high sensitivity and excellent selectivity, making them an attractive tool for the label-free, economical, and real-time detection of different targets. Portable devices work well as the accessory kits for LC droplet-based biosensors to make them easier to use by anyone for on-site monitoring of targets. Herein, we offer a review of the latest developments in the design of LC droplet-based biosensors for qualitative target monitoring and quantitative target analysis.

Liquid Crystal Biosensors: Principles, Structure and Applications.

Liquid crystals (LCs) have been widely used as sensitive elements to construct LC biosensors based on the principle that specific bonding events between biomolecules can affect the orientation of LC molecules. On the basis of the sensing interface of LC molecules, LC biosensors can be classified into three types: LC–solid interface sensing platforms, LC–aqueous interface sensing platforms, and LC–droplet interface sensing platforms. In addition, as a signal amplification method, the combination of LCs and whispering gallery mode (WGM) optical microcavities can provide higher detection sensitivity due to the extremely high quality factor and the small mode volume of the WGM optical microcavity, which enhances the interaction between the light field and biotargets. In this review, we present an overview of the basic principles, the structure, and the applications of LC biosensors. We discuss the important properties of LC and the principle of LC biosensors. The different geometries of LCs in the biosensing systems as well as their applications in the biological detection are then described. The fabrication and the application of the LC-based WGM microcavity optofluidic sensor in the biological detection are also introduced. Finally, challenges and potential research opportunities in the development of LC-based biosensors are discussed.

Interactions of a biological macromolecule with thermotropic liquid crystals: Applications of liquid crystals in biosensing platform

Liquid crystal biosensor was developed based on a 4′-octyl-4-biphenylcarbonitrile (8CB) by adsorption of biological macromolecule bovine serum albumin (BSA) at the 8CB interface. BSA was detected by examining the changes in the director configurations of 8CB molecules under a polarizing optical microscope. The transitions in the director configuration were due to the non-covalent bonds. This technique demonstrated high sensitivity at a concentration of 100 µM of BSA. The binding events between the 8CB and BSA were investigated through molecular docking studies that confirmed the protein-ligand interaction. The most probable binding location of 8CB to dock with BSA were determined at a subdomain IB of Sudlow’s site I. The active residues on analyzing were found to stabilize the 8CB molecules through different interactions. These active residues that were involved in the protein-ligand interaction were further confirmed with Raman spectroscopy. This study provided the vibrational properties and structural changes that occurred due to the various interactions between the 8CB and BSA. The results presented in this work lead to a potential biosensing tool for detecting and sensing proteins using LCs.

Highly sensitive and rapid detection of protein kinase C based on liquid crystal biosensor

Protein kinase C (PKC), a protein which is widely present in organisms, plays a pivotal role in the pathogenesis of many diseases, and has become a target for the diagnosis and treatment of many illness. In this study, a rapid method based on liquid crystal (LC) biosensor and nano-modified signal amplification technology for PKC detection is demonstrated. Glutaraldehyde (GA) was used to fix the PKC antibody/gold nanoparticles (anti-PKC/AuNPs) conjugations to the substrate mixed self-assembled with (3-aminopropyl)-triethoxysilane/N, N-dimethyl-N-octadecyl-(3-aminopropyl)-trimethoxysilyl chloride (APTES/DMOAP). The above processing maintained the LC molecules to arrange vertically and induced a dark background under polarized light. When PKC was presented, it would be fixed on substrate through binding with anti-PKC of the complex specifically. The specific binding event resulted in the change in morphology of the substrate, arrangement of the LC molecules and brightness of the LC film, thereby the sensitive detection of PKC was achieved. The developed biosensor present a good linear relationship between the average gray intensity of the optical imaging and the PKC concentration in a wide linear range of 10–250 ng·mL−1, the correlation coefficient was 0.997, and has a very low detection limit of 1.680 ± 0.005 ng·mL−1. The findings of this work provided a potential application for the high sensitivity and simple detection of protein kinases.

Development of liquid crystal biosensor for the detection of amyloid beta-42 levels associated with Alzheimer's disease

This study represents the development of a biosensor which is based on the liquid crystal (LC) orientation as a function of the peptide concentration to detect an amyloid-beta-42 (Aβ42) antibody-antigen binding events. The Aβ42 peptide binds to the Aβ42 antibody forming an immunocomplex which is immobilized on the Dimethyloctadecyl[3-(trimethoxysilyl)propyl] ammonium chloride (DMOAP) coated surface. The disturbed orientation of LCs as a result of the binding of the formed immunocomplex was observed using the polarized optical microscope (POM) as a function of decreasing Aβ42 peptide concentration from 1000 to 1pg/ml. The concentration, as low as 1pg/ml of Aβ42 peptide was able to be successfully detected in our system. Apolipoprotein E4 (ApoE4), that specifically bound to the Aβ42 peptide, was added into the system and a remarkable change in reflection spectra of samples was observed with increasing Aβ42 peptide concentration. The concentration of ApoE4 protein was detected in the range of 0.1-30nM by this system due to the interaction between the two proteins.