Cholesteric Liquid Crystals Sensors Based on Nanocellulose Derivatives for Improvement of Quality of Human Life: A Review

This paper presents a review of cholesteric liquid crystal (CLC) sensors based on water and hydroxypropyl cellulose (HPC) mixtures for healthcare and human quality of life applications. First, an overview of the sensors system demands for healthcare and environmental sensing is presented in which there is also a discussion on the sensors technologies conventionally applied in these scenarios. Then, a discussion of the water‐HPC mixtures and the formation of the CLCs as well as their operation principle and fabrication methods is presented. Thereafter, the applications of such technologies for the assessment of different parameters related to biomechanics, medical conditions, and environment contamination are discussed in detail. Thus, the use of CLC sensors based on HPC membranes provides novel sustainable approaches for highly sensitive sensors systems with intuitive signal acquisition and analysis. For these reasons, one can envisage a widespread of such technologies due to the mentioned advantages in conjunction with low cost, flexibility in fabrication, simple signal processing, biocompatibility, and biodegradability.


Introduction
The technological advances throughout the last decades enabled new approaches, developments, and paradigms in different areas.It is possible to mention such advances in the Industry 4.0, [1] the new developments of smart cities, [2] environmental sensing, [3] agriculture, [4] and the digital health. [5]The latter is responsible for many advances in medicine, which is translated to the public health in general [6] and resulted in quality of life, higher age expectancy and population ageing. [7]Recently, the COVID-19 pandemic highly increased the demands for new technologies and further advances in medicine not only on the pharmaceuticals development, but also remote health monitoring, biosensors for diagnosis and general digital health approaches. [8]Such improvements are important for early detection, monitoring and rehabilitation of patients not only with COVID-19, but also with many other clinical conditions that demand a continuous monitoring.
Among the different technologies and novel concepts in healthcare, [9] the internet of things (IoT) enables the interconnection of heterogeneous devices with wireless connectivity using the internet as a gateway and without human intervention. [10]In this case, there is a massive connection of multiple devices with demands of low latency and high reliability. [11]Such demands can be reached using the 5G networks that include important features for IoT applications, such as enhanced mobile broadband, ultrareliable and low-latency communications, and massive machine-type communications. [12]The massive interconnection of the devices, resulted in major hardware developments of different gadgets and devices with low power consumption and high connectivity in conjunction with micro-and even nanoscale dimensions for different healthcare applications. [13]n a different perspective, all technological advances bring an important issue to the environment, since the waste production is increasing throughout the years. [14]Among different materials, plastic and electronic waste (e-waste) are intimately related to such technological advances in massive interconnection of devices. [15]Considering the plastic waste, there is a 200-fold increase on the plastic production from 1950 (2 million tons per year) to 2015 (381 million tons per year) [16] in which around 40% of the produced plastic materials are employed on packaging of products of different industries. [17]However, only around 20% of such waste is recycled, [16] which leads to a high increase in the plastic pollution, one of the major environmental issues.The plastic pollution has harmful effects on the land itself, water, on animal life, public health and even in the air quality, since around 12% of the plastic residue is combusted. [18]If the e-waste is concerned, similar issues are verified, where 53.6 million tons of e-waste production is reported. [19]Comparing with previous years, e.g., 44.7 million tons in 2016, the annual growth rate of e-waste is around 2 million tons with small equipment as the product with higher e-waste generation. [15]Nevertheless, the e-waste pollution brings even higher harmful effects for human health, since the heavy metals, bisphenol A (BPA), dioxins, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) of such residue have harmful effects for the human health, as summarized. [19]he alarming issue of the waste and e-waste as well as their widespread in the last few years motivated new regulations and legislations related to recycling, [20] waste mitigation, [17] and carbon neutrality. [21]To that extent, different approaches to provide sustainable environment and green routes for technological developments are proposed throughout the years, as summarized. [22]One of the main approaches that enables the higher sustainability on technological advances is the development of sustainable materials. [23]Such materials are generally derived from biodegradable sources, including natural plants. [24]mong these developments, the functional materials based on nanocellulose are increasingly used in many scenarios with different applications, such as soft robots, [25] energy storage, [26] plasmonic devices, [27] drug delivery, [28] and coatings (including mechanical, [29] chemical, and biological [30] ) applications.Advantages such as biocompatibility and biodegradability motivated such important advances in the cellulose-based devices, as the cellulose also is the most abundant polymer on Earth, which result in higher availability and lower cost of the material. [25]ne of the most widely used configuration and arrangement of cellulose is on the form of microfibers that diffusively scatter the light, results in a white color. [31]If nanocellulose structures are considered, there is the possibility (by means of crystalline arrangement of the particles) of developing films with structural colors that are optically active as well as transparent films. [31]mong these different structures and possibilities of nanocellulose, there is a structure with hydroxypropyl groups as their building blocks, resulting in a mesophase in the hydroxypropyl cellulose (HPC). [32]The HPC/water binary solutions result in a liquid crystalline behavior with iridescent colors and chiral behavior due to the molecular arrangement in a helicoidal structure. [33]his structure is optically responsive in which there is a Bragg reflection with circularly polarized light sources, resulting in reflections in predefined wavelengths. [34]As the reflected wavelength follows the Bragg condition, at a predefined illumination angle, it is intrinsically sensitive to the pitch variation in the molecular structure, similar to the one conventionally obtained in fiber Bragg gratings, a well-known optical sensor technology, as summarized in ref. [35] The pitch variation in the chiral structure is sensitive to the strain (and all its variants) in the structure, resulting in a variation of the reflected wavelength (i.e., observed color).
To that extent, different applications of HPC-based structure have been proposed throughout the years such as motor devices, [36] smart structures, [37] and wearable devices. [38]his paper presents a review of HPC-based cholesteric structures development and applications on human health assessment, which can provide not only guidelines for the HPC/water liquid crystalline systems applications in sensors systems, but also in the new perspectives for developments of such sensors systems for healthcare.This paper is divided as follows.The general overview and perspectives of human health assessment and the role of the sensors in this scenario are thoroughly discussed in Section 2. Furthermore, in Section 3, the operation principle, formation of the HPC/water liquid crystalline systems as well as their fabrication and functionalization are discussed.The current applications and new perspectives of HPC/water liquid crystalline systems use in healthcare are presented in Section 4. Finally, conclusions and future works suggestions are discussed in Section 5.

Overview of Sensors and Devices for Human Life Quality
The notorious increase in the life expectancy of overall population is closely related to the major advances in medicine, public health, economy, and social development.Nowadays, diseases that were deadly decades ago, now are treatable or even eradicated. [39]Another important factor is the global reduction of the premature deaths, which also contribute to the increase of life expectancy.Such increase in the life expectancy leads to two main factors: i) the increase of the global population, which is now in the order of billions, instead of hundreds millions in 1950; [40] ii) The population ageing, where the number of elders (over 65 years) sharply increased in the last decades. [7]To support the continuous advances in medicine and quality of life, the technological advances in healthcare play a crucial role on the increase of the quality of life, where the advances in sensors systems, communication, system integration, and data processing are widely employed in the daily routine. [41]he demographic transition in the world population sets new challenges in different areas.Healthcare for the elderly population presents another challenge, as the elderly suffer from inherent aging conditions such as immunosenescence and urologic and sensory changes, including hearing loss, visual acuity degradation, and vestibular function impairment. [6]A variety of physical functions are affected by these conditions, including a reduction in walking speed, a reduction in mobility, difficulty carrying out daily tasks, and an increase in the risk of falling.In addition to deteriorating physical functions, cognitive impairment can also compromise psychological and social functioning. [6]As a result of population aging, there is also an increase in chronic agerelated diseases and geriatric syndromes. [42]These conditions include osteoarthritis, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and weakness of the skeletal muscles.In all of these conditions, physical and/or cognitive functions are impaired. [42]ealthcare technology advances provide new insights into rehabilitation and therapeutics, where wearable technologies have become increasingly prevalent in recent years with a significant impact on industrial manufacturing for these innovations in products, regulations, and data security. [43]Methods to increase patient engagement in the use of such technologies are also proposed. [44]Moreover, challenges related to technology sustainability, failure rates, privacy, and security have been addressed. [45]n conjunction with an increase in patient engagement, wearable assistive technologies have resulted in a continuous increase in the market for wearable healthcare devices, [9] where almost half (42%) of wearable devices are dedicated to healthcare applications.
Movement and physiological parameters for human health are increasingly measured and analyzed to provide novel developments in healthcare.This includes continuous monitoring of health conditions as well as the possibility of predicting some diseases and clinical disorders.As part of human health assessment, foot plantar pressure is monitored, which provides valuable information regarding human locomotion. [46]In the course of plantar pressure assessment, it is possible to obtain a foot pressure distribution map, which plays an instrumental role in monitoring foot ulcerations (especially in diabetic patients).Moreover, foot pressure maps enable the measurement of foot-function indices, such as the arch index, which enables the evaluation of each individual's arch type, which is also related to injuries sustained by runners. [47]Additionally, the dynamic evaluation of foot plantar pressure can also assist clinicians in diagnosing gait-related pathologies. [48]atient monitoring parameters include biomechanical metrics, which are subdivided into kinematics and kinetics.Such parameters provide crucial information about an individual's physical condition and are directly related to the performance of daily activities as well as locomotion. [49]Human movement biomechanics is the study of the mechanical characteristics and aspects of human movement. [50]In addition to movement analysis, gait analysis comprises the systematic study of human walking, which involves collecting kinematic and kinetic data. [51]Kinematic assessment describes body motion without taking into account the causes of the motion.The kinematic parameters include joint angles, center of mass (CoM) displacement velocity, and spatiotemporal gait parameters such as cadence, stride, and step length, among others as discussed. [49]Spatiotemporal gait parameters describe foot placement, gait event timing, and velocity variables.Angular and displacement data are complementary to the assessment of such parameters in gait kinematic analysis.In the movement's kinetics assessment, the forces and torques that initiate the movement are analyzed.This study also considers the forces generated within the body that result in human movement. [51]Kinetic parameters include ground reaction forces (GRF), plantar pressure distribution, and joint momentum. [52]s a conventional approach for the assessment of such biomechanical parameters, different electronic [53] and optoelectronic [54] approaches have been proposed throughout the years.The general drawbacks of these electronic-based approaches are their electromagnetic sensitivity, necessity of constant calibrations, complexity in signal processing in some cases and the use of additional gadgets (such as displays and dataloggers) to provide intuitive data to the users.
In addition to the necessity of biomechanical assessment, the biomedical sensors also include the use of different plasmonic approaches for detection of different compounds, which include hormone, bacteria, virus, and so on.Plasmonic sensors are part of optical-based affinity sensors and can be used in many fields and applications, including clinical analysis, environmental pollution control, food, agriculture, veterinary, disease diagnosis and monitoring, pharmaceuticals, immunoassays, industrial processing, among others. [55,56]These type of sensors allow realtime monitoring, and other advantages such as fast analysis time, high sensitivity, and low cost, whereas classical analytical methods are not capable of these feats. [57]These sensors' sensing region is usually composed of metal or metal-dielectric nanostructures, for example, gold and silver, that are usually chemically modified to immobilize the biorecognition elements (functionalization process), allowing the capture of specific target analytes.
Hormones play an important role in both diagnostics and antidoping control.Some studies are provided by different authors that cover plasmonic sensors for hormone detection, providing interesting solutions to implement in this clinical area.In the literature, we can find several works related to the detection of cortisol (stress hormone) using different configurations of plasmonic sensors.Some examples of those studies are presented below.
For instance, Jung et al. [58] developed a localized surface plasmon resonance (LSPR) immunosensor for stress hormone (cortisol) detection (Figure 1).In this study, cortisol molecules were chemically conjugated to 2, 5, 30m, 40 nm Au NPs and 14 nm ZnO NPs to enhance the LSPR detection signals.Furthermore, cortisol monoclonal antibody (c-Mab) was immobilized on the Au NPs layered sensor chip.The target (cortisol conjugated NPs) was immune-bounded or detected to the c-Mab immobilized Au NPs sensor chip.ZnO NPs were used for comparison with Au NPs since those NPs are nontoxic and biocompatible to human applications, and a sensor fabricated with these NPs is capable to operate in the visible and close to ultraviolet spectral regions.This work proved that the conjugation of cortisol to both Au and ZnO NPs enhanced the direct LSPR detection of the cortisol, although there was an extra process to conjugate the cortisol molecule preventing the detection of cortisol by itself for direct LSPR signal.
Another example of a plasmonic sensor for cortisol detection was developed by Pandey et al. [59] Their work reports the detection of salivary cortisol using a plasmonic grating-based fiber optic surface plasmon resonance (SPR) sensor (Figure 1).The fiber surface is covered with a thin Ag layer.Gratings of SiO 2 and SiC (one at a time) are then applied in combination with the Ag film.Furthermore, the angular interrogation mode is applied in this study in which the sensing mechanism is based on the power loss (PL) variation with the angle of incidence ().Besides, the Ag layer was also optimized until a maximum PL was achieved, corresponding to cortisol concentration variation.Sensor analysis based on the intensity interrogation method is also presented in this study.With the angular interrogation mode, was possible to attain limit-of-detections (LODs) of 9.9 and 9.8 pg mL −1 for SiO 2 and SiC-based sensor designs, respectively.Whereas LODs of 22.6 and 68.17 fg mL −1 were obtained for SiO 2 and SiC-based sensor designs, respectively, when using the intensity interrogation method.This last method presented a better LOD than when determined by angular interrogation mode.Nonetheless, both results are considered by the authors better than the present-stateof-art related to cortisol monitoring.
Besides de detection of very low molecular weight hormones, the detection of peptide hormones such as insulin has also been  [58] Copyright 2023, Springer.b) Representation of the grating-based fiber optic SPR sensor, in which D is the fiber core diameter, L is the sensing region length, d is the grating period, and d1 is the groove width.Reproduced with permission. [59]Copyright 2020, Elsevier.c) Schematic representation of SPR aptamerbased insulin sensor in a four-channel microfluidic format.Reproduced with permission. [60]Copyright 2020, Elsevier.d) Schematic representation of T4 detection using anti-T4/C-AuNPs nanoprobe.Reproduced with permission. [61]Copyright 2020, ACS.e) Schematic representation of EE2 detection using cellulose fiber yarns modified with cyclodextrins.Reproduced with permission. [62]Copyright 2018, ACS.
studied.This hormone allows the regulation of carbohydrate metabolism, therefore, is very important for clinical diagnostics and for patients with different types of diabetes. [63]This disease can appear due to the deficient insulin secretion by pancreatic -cells leading to imbalanced insulin levels, but also, cells for glucose metabolism cannot recognize elevated levels of this hormone.For the diagnosis of types of diabetes, is of utmost importance the detection and monitoring of these hormone levels in complex clinical matrices. [60]or instance, Singh [60] developed work for insulin detection which consisted of an SPR aptamer-based insulin sensor in a four-channel microfluidic format (Figure 1).This sensor uses antibodies attached to magnetic NPs in order to capture insulin from serum samples of a patient with diabetes and plasmonenhancing quantum dots for signal amplification.This sensor monitors insulin levels in twice-diluted serum.For a linear detection range of 0.8-250 pm, this sensor achieved a LOD of 800 fm.This study also demonstrated that measured insulin levels using this sensor were in close agreement with the standard enzymelinked immunosorbent assay (ELISA) measurements.
Other peptide hormones have also recently been detected using plasmon sensors, such as pituitary hormones.In particular, thyroid stimulating hormone (TSH) was detected in human blood serum by Salahvarzi et al. [64] using an LSPR-based gold nano biosensor.For this purpose, AuNPs were synthesized and the anti-TSH antibody was immobilized on their surfaces by electrostatic adsorption.Dynamic light scattering was applied and the LSPR peak shift resulting from the TSH antigen capture by the antibody was monitored.For a linear dynamic range of 0.4-12.5 mIU L −1 was attained a calibration sensitivity of 1.71 L mIU −1 .The human control serum sample was also analyzed for TSH and acceptable results were obtained.This hormone plays an important role in the regulation of the body's metabolism, temperature, weight, and cholesterol, and stimulates the biosynthesis and secretion of thyroid hormones, such as triiodothyronine (T3) and thyroxine (T4) into the blood. [65]For instance, T4 is an essential hormone for cellular metabolism and neural development, being a reliable diagnostic biomarker.Mradula et al. [61] created and tested an immunosensor for the detection of T4 (Figure 1).In this work, antibodies were immobilized onto AuNPs using cysteamine as the intermediate linker.This was the first study of T4 detection that used AuNPs as an optical sensing platform.In this way, Cysteamine-capped gold nanoparticles (C-AuNPs) were synthesized by sodium borohydride reduction methods and, then the antibody anti-T4 was immobilized on C-AuNPs using EDC/NHS (1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride / N-hydroxysuccinimide) coupling chemistry.In this sensor, the binding between the T4 hormone and the anti-T4 antibodies leads to a change in the SPR angle only, resulting in the decrease of the absorbance intensity for a specific wavelength without redshift.Using this mechanism was possible to test this immunosensor for different T4 concentrations.For a linear range of 0.52-65.1 pg mL −1 was possible to attain a LOD of 9.11 pg mL −1 .
As can be seen, many studies were carried out for the detection of hormones using plasmonic sensors, in which a few examples of more recent work were aforementioned for the detection of some hormones.However, works that make use of plasmonic sensors for this purpose employing cellulose materials or more specifically HPC are still not easily found in the literature.A study that was found in this area, was reported by Orelma et al. [62] This study consisted of a sensing platform for the capture of 17-ethinyl estradiol (EE2) from water (Figure 1).EE2 is a synthetic estrogen hormone used as contraceptive.Therefore, cellulose fiber yarns were modified with cyclodextrins using adsorbed chitosan.The capture of EE2 by the cyclodextrin-modified cellulose was confirmed via online detection with SPR.This study represents advancement and indicates excellent perspectives for inexpensive platforms using cellulose materials for hormone capture.
Diseases caused by pathogenic bacteria due to the consumption of contaminated water and food are a major worldwide concern.This problem is more observed in developing countries where hygienic conditions are poor and the water supply is not treated.In this sense, many studies have been developed to detect bacteria.
To name a few, Liu et al. [66] reported a liquid crystal (LC)-based optical aptasensor for the detection of E. coli, a model of Gramnegative bacteria.LC molecules can arrange themselves in an orderly or disorderly way due to different stimuli.In this study, a mixture solution of aptamer and hexadecyl trimethyl ammonium bromide (CTAB) was left in contact with the segmented LC films on a copper mesh.The sensing mechanism in this study is based on the liberation of the CTAB molecules by the binding of aptamers with the target bacteria.Then, these molecules self-assemble at the LC-aqueous interface, inducing the vertical alignment of LCs.Owing to this phenomenon, it will be observed an optical transition from bright to dark due to the LC molecular orientation.With this sensor was possible to achieve an ultralow LOD of 27 cfu mL −1 .Zafiu et al. also developed LC-based sensor for bacteria detection, in which LC was covered with Lipopolysaccharides (LPS) monolayers.Three different LPS were studied to investigate their potential as a sensing layer to detect bacteria, in which LPS O127:B8 was identified as the most useful biomimetic sensing surface.With this sensor is possible to detect bacterial presence since can interact with three different bacteria species, one gram-positive and two gram-negative species. [67]everal plasmonic sensors have also been reported in the literature for bacteria detection.These types of sensors present several advantages such as sensitive, rapid recognition, real-time analysis, portability, no need for labels, selective sensing, and simplicity in identifying target analytes. [56]Among many others, Kaushik et al. [68] reported an SPR immunosensor for E. Coli detection composed of an Au-coated etched optical fiber with MoS 2 nanosheets functionalized with anti-E.coli antibodies.Besides, a conventional optical fiber immunosensor was also studied for comparison.Kaushik et al. [69] developed a single modetapered multimode-single mode (SMS) immunosensor modified with anti-Salmonella typhimurium antibodies for Salmonella typhimurium detection.A tapered single-mode-no-core-singlemode fiber coupler (SNSFC) structure was used to produce an immunosensor for S. aureus detection and reported by Chen et al. [70] For this purpose, no-core fiber was tapered and modified with pig IgG antibodies.
Nonetheless, these sensors do not employ cellulose materials for the purpose of detecting bacteria.Lately, plasmonic sensors that employ bacterial cellulose (BC) as a base component for realizing green transducers, not specifically for bacterial detection, have gained interest and have been observed in the literature.For example, Cennamo et al. [71] developed a plasmonic sensor based on BC.In this study, a thin Au film was sputtered on a green composite based on BC that was used as the optical waveguide to obtain an LSPR sensor.Furthermore, fibers were used to connect the green disposable optical sensor with a light source and a spectrometer.Since it is a new configuration, this sensor was tested by measuring the refractive index of different water-glycerin solutions.According to the attained preliminary experimental results, this platform showed capabilities to be used to make environmentally friendly LSPR sensors, useful to realize disposable biosensors.In the same year, Cennano et al. [72] reported the same sensor but with a novel plasmonic sensing approach.In this case, was tested two different optical waveguide configurations of BC, with and without ion liquids inside BC in order to attain mechano-electric transducers.Therefore, it was investigated the influence of the thickness and the dimensions of the BC papers on the optical responses.This sensor was also tested by measuring the refractive index of different water-glycerin solutions.In terms of intensity variation, was possible to obtain a sensitivity of 13.54 a.u.RIU −1 for BC paper without ions and 2.23 a.u.RIU −1 for BC paper with ions.The sensitivity considering the resonance wavelength shift for BC paper without ions and with ions was, respectively, 1600 and 980 nm RIU −1 .Therefore, the best performance was achieved without ions in the BC paper.Purwidyantri et al. [73] developed another plasmonic sensor using BC Nanofibrillation.In this study, the cellulose base source was a food product nata de coco (NDC).This NDC was treated with high-pressure homogenization (HPH) to obtain highly dense nanofibrils.Afterward, this compound was transformed into a thin paper sheet.This homogenized BC (HBC) was compared with the normally agitated bacterial cellulose (BC) and AgNPs were incorporated to produce plasmonic papers for application as surface-enhanced Raman scattering (SERS) substrate.These sensors were studied for the Rhodamine 6G (R6G) molecule, in which the plasmonic HBC paper sheet provided more prominent SERS signals than the plasmonic BC with a limit of detection of ≈92 fm.This happens because of the better adsorption of AgNPs and the generation of effective SERS hotspots due to the high surface roughness and improved textural properties of HBC.
In order to treat and mitigate the clinical and health issues, the pharmaceuticals development plays a key role on the public health evolution, advances in medicine and human life quality. [74]n this case, the sensors and general developments in Industry 4.0 can enable novel developments in pharmaceuticals.[75] For this reason, sensors that can aid on the pharmaceutical developments are developed throughout the years.[76] In addition, the environmental pollution plays an important role in the quality of life, since it can be related to health conditions, especially respiratory clinical conditions.[77] It is also important to mention that laws and regulatory measurements have been applied on the carbon footprint reduction as well as the reduction of greenhouse gases.[21] For this reason, the demands of sensors for gas assessment and detection are increasingly desired.
Considering the high demands for sensors systems previously mentioned in conjunction with the increasing demands on the development of green and sustainable routes and approaches, [78] the development of cellulose-based sensors devices present important advantages due to their biocompatibility and sustainability. [28]Furthermore, the natural abundance of cellulose-based materials also provides advantages on the material availability and potential of low-cost applications. [31]It is also important to mention that the optically responsive polymers and their applications in liquid crystal sensors are able of providing a straightforward visualization of the results, since it is visible for the user.Such feature is important in certain applications, where there is the possibility of direct assessment of the measurand by the user, which provides important advantages especially for users that are not familiar to technological gadgets.This feature provides a key advantage for the sensor system usability and potential for widespread.Thus, the use of cellulose-based materials and liquid crystals for different sensing applications is summarized in Figure 2, where it is possible to observe the different scenarios in which the liquid crystal sensors can be applied.The applications of such sensors' approaches in these scenarios are further discussed in the next sections.

Hydroxypropyl Cellulose-Based Responsive Photonic Structures
The HPC is a water-soluble cellulose ether conventionally employed as colloidal stabilizers, flow modifiers, and surface-active polymers. [79]In decades ago, the first reports on the water-HPC mixtures forming a cholesteric structure that stabilizes at a predefined temperature according with the HPC concentration as shown in Figure 3. [80] In addition, such mesophase result in a liquid crystal optically responsive as a function of different parameters. [31]iquid crystal (LC) sensors are a type of sensor that utilizes the properties of LC to detect changes in environmental conditions.These sensors have been used in a wide range of applications, including medicine and public health.
In medicine, LC sensors have been used, for instance, to detect changes in temperature, [81] pH, [82] and other parameters that are important in medical diagnostics.LC sensors have also been used for monitoring of patients with chronic diseases, especially diabetes.LC sensors have been used to measure glucose levels in blood, which is an important parameter for diabetes management. [83]These sensors have also been used to detect the  [88] Copyright 2022, Springer.
presence bacteria or virus in the human body, biological fluids as well as in the environment. [66,84]esides medicine, LC sensors have also been used in public health to detect changes in environmental conditions that can impact human health.For example, LC sensors have been used to monitor air and water quality, [85] as well as to detect the presence of pollutants [86] and toxins. [87]The reliable and quickly acquired information can be useful for identifying areas where there is a high risk of exposure to harmful substances, and for taking steps to mitigate that risk.
Overall, LC sensors have proven to be a valuable tool in the field of medicine and public health.Since they are versatile, sensitive, and can be used to detect a wide range of environmental conditions.

HPC Formation and Fabrication
The conventional method to dissolve the HPC in water generally occurs by mechanical stirring in a slow process, which requires a long time for the unentangling of the polymer chains. [79]The concentration of the HPC is related to the state of the water/HPC mixture. [89]It is also important to mention that the HPC is soluble only in temperatures below 42 °C, which is the lower critical solution temperature (LCST). [24]In temperatures higher than LCST, there is a phase separation in the mixture that can harm the functionality of the liquid crystal.In addition, such effect is due to the anisotropic nature of the mixture, which only occurs in concentrations higher than around 38%.Thus, the HPC concentrations in the mixture are generally higher than 38%, typically ranging from 38% to 65%, where the concentration is also related to the reflected wavelength (or color, in the visible wavelength range) according to the water-HPC diagrams, such as the one presented in Figure 3.It is also worth to mention that the HPC is not only dissolved in water, there is the possibility of using acetone in the mixture to obtain HPC-acetone structures such as the ones presented [90] for liquid crystal applications.
In order to improve the diffusion in the mixture, the hygroscopic method was proposed, [91] where an environment with controlled humidity.In this case, there is an initial formation of an isotropic structure, which is controllable slow drying of the sample for higher control of the anisotropic phase formation.The proposed method enables the formation of stable structures for the development of filament shape forms in which filaments as thin as 1 mm diameter were presented.Thus, this method provides higher controllability into unconventional shapes, since many LC applications involve the development of thin films, the use of the cylindrical shape is important for sensors applications in which there is the necessity to embed the HPC-water solution in different surfaces geometries without harming the uniformity of the LC sample.
In another method for high controllability of the LC structures, the soft lithography was proposed, [31] where the sample formation and molecular arrangement can be achieved faster than days or weeks as conventionally obtained in traditional mechanical mixing methods.The method is based on the development of a Polydimethylsiloxane (PDMS) mold, which is pressed against the HPC solution.The HPC membrane is formed by pressing the solution following the hot embossing method, resulting in the development of structures with higher optical quality and different geometries.In this approach, it is also possible to add dopants in the HPC membrane to increase the photoluminescence.Thus, the soft lithography is another method with the possibility of providing fast fabrication of the HPC membranes with high customizability.
It is also important to mention that the aforementioned methods generally needs long processing times and necessity of manual processing in some cases that are unsuitable for batch fabrication.To address this issue, a roll-to-roll fabrication method was proposed [37] for the HPC membranes fabrication.In this case, the mixing of the HPC-water solutions is performed using a mechanical mixer, which also leads to bubble/air voids formation in the HPC solution, where a centrifuge is used to remove such bubbles prior to the HPC solution feeding in a peristaltic pump.In order to avoid the samples drying, the samples are sealed using a UV-curing adhesive during the lamination phase of the HPC structure, which provides the samples thickness.Then, the samples are rewinding forming long rolls of HPC membranes, suitable for industrial scale production and applications.
Following recent trends in manufacturing, the 3D printing was also applied on the HPC solution processing. [33]The motivation for such developments is related to the relative fast fabrication using such additive manufacture technique in conjunction with its high customizability. [92]To that extent, the use of HPC solution as the feeding material in 3D printers, the solution needs further processing (and functionalization in some cases).The use of the HPC solutions in 3D printers is enabled by combining the HPC solution with photo-crosslinking elements in which the filaments with chiral structure are subjected to a UV curing after their processing.This method enable a high degree of customization using a single step fabrication with a fast processing (in the order of hours or even minutes, depending on the printing size).
In this section, different methods for HPC fabrication and processing of the membranes to obtain customizable geometries.The discussed methods are related to the direct mechanical mixture of the samples, which is conventionally applied on the HPC solution formation with the additional possibility of using mixers, where the latter has the drawback of adding bubbles/air voids in the HPC solution.Aiming at a higher controllability of the process and optical quality, the hygroscopic method presents advantages due to its controllable drying of the HPC solution, which leads to the possibility of obtaining filaments with small diameter.However, the hygroscopic method still needs long  [31,33,37,91] Copyright 2023, Nature, Wiley and EPJ E.. production times that can be an important drawback in some applications.For this reason, the soft lithography method can be used as an approach for faster processing without a critical harm on the surface and optical qualities of the HPC membranes.The comparison of such methods is presented in Figure 4, where it is possible to observe the advantages and drawbacks of each technique.In addition, Figure 4 includes the comparison of the fabrication methods focused on the film formation, namely the roll-to-roll fabrication method in which long rolls of HPC membranes are fabricated using lamination followed by the winding of such rolls.In another innovative method for HPC membranes and structures fabrication, the use of 3D printing fills the gaps of the lamination processing method due to the higher shape, dimensions, and geometries customization provided by the 3D printing method.Therefore, the fabrication methods discussed provide specific features, useful in different applications and the choice of the fabrication method is a parameter to be considered according to the desired application.

HPC/Water Liquid Crystalline System Operation Principle
Some substances, when transiting from the solid state to the liquid state, present one or more intermediate phases (called mesophases) with mechanical properties identical to those of liquids but with anisotropic optical and electrical properties typical of solid crystals.Thus, the intermediate liquid phases of these substances, when observed under a microscope between crossed polarizers, reveal magnificent optical textures characteristic of the anisotropy of the medium, optical images which disappear if the substance transits to the isotropic liquid phase.Substances that exhibit these intermediate phases have been given the name of liquid crystals. [93]The attaining of a mesophases can be achieved by temperature variation (thermotropic mesomorphism), or by the influence of a solvent (lyotropic mesomorphism). [94]aking into account the shape of the molecules that constitute them, thermotropic LC can be subdivided into calamitic and discotic. [93]Calamitic LC are composed by elongated molecules having a relatively rigid central part and flexible aliphatic chains at the ends.In discotic LC, as the name suggests, the molecules are disc-shaped and also have a central rigid body to which various aliphatic chains are attached, which tend to be arranged in the plane of the body. [95]alamitic LC can present different types of polymorphisms, namely exhibiting nematic, smectic, and cholesteric phases. [93]n the nematic phases, the molecules have, on average, a tendency (in macroscopic domains) to align themselves according  [97] Copyright 2022, John Wiley and Sons.
to a preferential direction n, being this vector called the director, with their centers of mass being randomly distributed in space (Figure 5 left).This orientation of molecules extends over long distances and nematic monodomains can be obtained using external stimuli such as electric or magnetic fields.These mesophases typically present low viscosities around 0.1-0.2Pa s. [96] The nematic phases are usually positive uniaxial mediums, having the optical axis along the director.On a decreasing temperature from the isotropic phase, the nematic phase usually follows the isotropic phase and appears before other more ordered phases, such as the smectic ones (phases where the molecules are organized in layers). [94]he cholesteric phases are twisted nematic phases in which, in their normal state, the molecules are arranged in helical configurations.These phases can be obtained with intrinsic chiral molecules or by dissolving chiral molecules into nematic compounds (Figure 5 right).The pitch of the cholesteric helix is a function of pressure, temperature, and also external fields, namely electric and magnetic fields.This mesophases, such as the nematics, present low viscosity, but are negative uniaxial since the optical axis overlaps with the axis of the helix.These phases are optically active exhibiting a very high rotational power. [98]ne of the most used techniques, for the characterization of LC phases, is the observation of textures using a polarized light microscope. [93]These studies started in 1922 by Friedel when the textures of LC were exhaustively studied and, based on these observations, a classification of these materials was proposed.However, it is necessary to emphasize that different textures may or may not correspond to different structures (different phases) and therefore, in case of doubt, it is necessary to resort to other methods, namely X-ray diffraction [98] or Nuclear Magnetic Resonance [99] to better determine, which phase a certain compound presents at each temperature or specific anisotropic parameters of that phase.
Due to their unique properties and versatility, LC are used in several technological applications such as displays and sensors. [100]On the scope of this review, the application in displays will be mentioned, since the principles behind the working mechanism are similar to the ones in sensors.
There are several techniques for building liquid crystal displays to be used in all sorts of displays (mobile phones, laptops, watches, calculators, information signs, car dashboards, etc.). [101]he majority of them have their working mechanism based on the TN (twisted nematic) which is one of the first liquid crystal display configuration to be developed.In the TN display, a nematic liquid crystal is used which is introduced into a cell limited at the tops by two transparent glasses, each one with a deposit of a transparent conductive oxide (electrodes).The inner surfaces of the glass plates that are in contact with the liquid crystal are previously prepared in such a way as to force the nematic molecules next to them to be oriented parallel to the glasses (planar alignment) but with the director rotated by 90°when passing from one plate to the other. [101]In this way, the two boundary conditions induce the molecules of the liquid crystal to arrange themselves, inside the cell, according to a helical configuration, similar to that observed spontaneously in cholesterics.The cell is limited by two crossed polarizers in such a way that depolarized light radiation passing through one of them, leaves it with the luminous vector E vibrating according to the direction of alignment of the molecules next to the nearest glass face.This direction of vibration is, however, rotated, due to the helical structure adopted by the liquid crystal, in such a way that the emerging light finds the second polarizer in full transmission conditions. [101]Under these conditions, in the OFF state, without the application of an electric field, the display is bright.If a nematic with positive dielectric anisotropy is used, when an electric field is applied between the electrodes, the molecules tend to align along the direction of the applied electric field. [98]Under these conditions, linearly polarized light emerging from the first polarizer passes through the liquid crystal volume without any rotation of its polarization direction, thus becoming extinct upon passing through the second polarizer (crossed with respect to the first one).Under these conditions, in the ON state, with an applied electric field, the display is dark. [93]ue to the fact that LC are sensitive to external stimuli and have optical anisotropy, they are often used as sensors and signal transducers.

Quality of Life Improvement
Considering the applications in human quality of life discussed in Section 2 in conjunction with the developments of LC sensors, in particular the ones using HPC solutions, discussed in Section 3, the applications of such LC sensing technologies are thoroughly discussed in different relevant scenarios for healthcare and general quality of life improvement.Among the multitude of parameters and measurands applications, the strain/stress Figure 6.LC sensors applications overview in strain and stress sensing.a) Tactile sensor.Adapted with permission. [34]Copyright.b) Operation principle with wavelength variation.Adapted with permission. [34]Copyright.c) Movement analysis.Adapted with permission. [38]d) Plantar distribution sensor.Adapted with permission. [37]Copyright 2023, Nature, Wiley.
sensors play a critical role on the movement analysis, [102] pressure distribution, [103] and activities monitoring. [104]In addition, temperature sensing is relevant for environmental sensing and microclimate conditions assessment, where the applications of LC sensors for the assessment of such parameters are discussed due to their relevance in the healthcare and quality of life management.Similarly, the detection of chemical compound in gas state is critical for the environmental sensing, since it provides important information regarding pollution levels with major influence on respiratory diseases and overall quality of life. [105]In other medicine applications, the LC sensors can also be applied on the assessment of bacterial infection, cancer cells detection and even on the DNA sensing.For these reasons, the LC sensors are able of detecting and monitoring physical and physiological conditions of patients as well as the environmental conditions.Furthermore, the LC sensing technology also plays a role in drug development, since the chirality and morphology sensors can be used on the identification and differentiation of different compounds (such as chiral amines) as well as the assessment of the morphology of different micro/nanoscale structures.Such LC sensors applications are presented in this Section.

Strain and Stress Sensors
One of the main applications of the cholesteric liquid crystals using HPC solutions is the possibility of measuring strain or stress in the HPC membranes. [34]The mechanical parameters measurement is based on the Bragg reflection at specific wavelengths, where the reflected Bragg wavelength is proportional to the refractive index of the liquid crystal, pitch of the cholesteric phase and angle of reflection. [34]Thus, for a constant angle of reflection, the pitch of the cholesteric phase changes as a function of the strain transmitted to the LC sensor. [106]In addition, the photoelastic effects can also occur in case of mechanical loadings applied on the HPC membrane in which there is a variation on the refractive index as a function of the strain applied in the membrane.Thus, when a strain (or stress) is applied on the LC sensor, there is a wavelength shift proportional to the mechanical loading, which leads to the possibility of measuring strain, displacement, angle, force, and pressure. [24]Figure 6 shows the overview of the operation principle of the LC sensors for strain assessment.
Considering the background and possibility of mechanical loading assessment using the LC sensors, developments, and applications of such technologies were proposed in smart structures and wearable sensors technologies. [38]To that extent, the development of a tactile sensor was proposed, [34] where a HPC membrane with PDMS encapsulation that changes its color (from red to blue) as the pressure is applied on the membrane.However, an important issue in HPC membranes applications is their sensitivity to the reflected angle, as previously mentioned, the reflected wavelength is also sensitive to the reflected angle.As schematically presented in Figure 6, the reflected angle leads to differences in the reflected wavelength acquired by the detector, which places important limitations in practical application of such sensors, since the detector placement and assembly needs careful positioning to avoid errors due to the reflected angles variation.In an attempt to tackle the issues of LC mechanical sensors based on HPC membranes, some approaches have been proposed to avoid the material's drying, such as the doping with glutaraldehyde (GA) proposed. [106]In this case, the crosslinked HPC membranes were developed and show relative wavelength insensitivity as a function of the observed angles, where the highest divergence as a function of the angle was the spectral intensity.
The developments in the LC sensing technology enable important applications in the healthcare field, such as the plantar pressure unit presented, [37] where the plantar pressure map can be obtained with centimeter resolution using a smart force platform based on HPC membranes.In another important application, a wearable sensor system based on HPC films were developed for movement analysis. [38]In this case, the HPC films are also combined with shape memory adhesive substrate for the development of a sensing patch capable of detecting movement through the strain transmitted to the LC sensor.

Temperature Sensors
As mentioned earlier, cholesteric liquid crystals (CLC) have important optical properties.In particular, it should be noted that when a light beam with a certain wavelength travels through a cholesteric single crystal in a direction that is parallel to the helix axis of the material, the beam is generally decomposed into two components with circular polarization (one left and the other right) one of which is almost totally reflected while the other is transmitted, all depending on agreement or discordance between the sense of rotation of the electromagnetic radiation vector E and the natural sense of torsion of the cholesteric helix. [98]For the light incidence under the defined conditions, it is verified that the maximum reflection occurs for a wavelength () that depends upon the pitch (P) and the average refraction index (n) of the material according to the de Vries expression  = n.P.sin (), where  is the angle between the incident light and the cholesteric layers. [107]In general, cholesterics exhibit a colored appearance when irradiated with white light, the observed color being a function of the reflected wavelengths (Bragg reflection) as can be seen in Figure 7.
As the pitch of the helix is a function of the temperature, by varying it, color variations corresponding to the zone of wavelengths of maximum reflection can be obtained.Nowadays, it is possible to obtain cholesterics or mixtures of cholesterics that exhibit color changes from red to violet in desired temperature domains (large or small ranges).This liquid crystal transduction capability is used in biomedical engineering and clinical applications, in techniques such as medical thermography, or simple body temperature measurements. [108]As an example, in Figure 8 encapsulated small droplets of a cholesteric liquid crystal on a black background reveals an image obtained after contact with the human body.In this image, the color variations correspond to local temperature variations.
Recently a liquid crystal thermometer was developed that is visible in images acquired by MRI (Magnetic Resonance Imaging).The weak magnetic field used in medical applications does not interfere with the cholesteric-isotropic phase transition temperatures of LC and when placed next to the body to be observed by MRI it is possible to have an indication of the local temperature. [110]gure 7. Schematic representation of the cholesteric phase with a demonstration of selective reflection.The central illustration demonstrates the general molecular structure of CLC systems.The chiral dopants have stereospecific centers that induce the helical twist in the host mesogens.A typical calamitic achiral LC molecule and a typical chiral dopant molecule are shown as an example (left), each with a rigid mesogenic group and flexible spacer unit(s).On the right is a schematic representation of the classical reflection band induced by planar-aligned CLCs, which is often characterized by transmission spectra.The notch in the transmission spectra represents the reflection center ().In some other works where reflection spectra were used,  is presented as the wavelength at the peak.Reproducedunder the terms of the Creative Commons CC BY license. [108]Copyright 2021, The authors, published by John Wiley and Sons.

Chirality Sensors
If a molecule is nonsuperimposable to its mirror image, is said to be chiral (they lack a plane of symmetry).Chiral compounds have a handedness, left or right.Right and left-handed molecules of the same compound are called enantiomers.For some reason, Nature favors the creation of left-handed proteins and righthanded carbohydrates.If one enantiomer of a certain compound is to be used in medicine for a certain purpose, careful must be taken in the administration of the drug, since the other enantiomer might be toxic.In the past, in the early 1960s, one of the enantiomers of a drug prescribed to pregnant women against seasickness (thalidomide) turned out to cause limb malformations on the fetus. [111]he LC sensing capabilities might be used to detect if a compound is chiral and if so, what is its handedness.It is possible to visualize in a polarized optical microscope the topological defects exhibited by droplets of nematic liquid crystal of toroidal topology crossed by fibers suspended in the air.The liquid crystal molecules tend to line up tangentially at the fiber surface and homeotropically at the air interface, which gives rise to the appearance of a ring-shaped line of topological defects around the main axis of the fiber at the center of the droplet. [112]f droplets of nematic liquid crystal are suspended in chiral and achiral fibers, it is possible to identify differences in the topological defect that appears around that fiber.If, for example, cellulosic fibers are produced by electrospinning, from anisotropic solutions of hydroxypropylcellulose (chiral) and isotropic solutions of cellulose acetate (achiral), and in both droplets of nematic liquid crystal are suspended, it is possible, without recourse the other technique that identifies the chirality of the compound, to distinguish which fiber is chiral and which is achiral, as can be seen in Figure 9.
Naturally on the surface with the atmosphere, the molecules of the nematic liquid crystal 5CB adopt an homeotropic alignment,  [109] Copyright 2022, John Wiley and Sons.however, it is possible to induce a planar alignment (parallel to the surface), if this interface is coated for example with glycerol.Liquid crystal droplets with homeotropic or planar anchoring on the outer surface of the droplet can be used to determine the fiber's chirality.Droplets with homeotropic anchoring at the liquid crystal-air interface, for chiral and achiral fibers, show a ring defect in the middle of the droplet around the fiber.However, this ring is tilted with respect to the fiber axis if the nematic droplet is suspended on a chiral fiber.Fiber chirality can also be determined in droplets with planar anchoring on the outer surface.Polarized optical microscopy images of liquid crystal droplets with planar anchoring on the outer interface are dark and quite uniform in the achiral fibers.On the other hand, droplets suspended in chiral fibers appear in polarized optical microscopy as very bright and having a nonuniform texture. [113]

Morphology Sensors
The same technique that consists of suspending droplets in fibers/filaments can be used as a way of differentiating morpho-logical properties of these fibers/filaments and correlating them with their mechanical properties.
This method has advantages over conventional observation techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), since it determines the conformation of structures on the fiber surface at a molecular scale, without the use of sophisticated equipment besides being carried out under ambient conditions.
If microfilaments with the same dimensions, from similar plants, which present different surface roughness (observed by SEM for confirmation), as can be seen in Figure 10, and different mechanical properties (evaluated using a fiber tensile testing machine), it is possible, through the observation of the formed topological defects in the suspended liquid crystal droplets, to identify these differences imperceptible to the naked eye.
In both cases, there is a crystal-liquid-air interface where the anchoring is homeotropic.In the droplet suspended on the microfiber which has a higher roughness, a homeotropic alignment also develops next to the surface of the microfilament.In the Figure 9. Nematic droplets as chiral sensors for biofibers.A) A cellulose-based electrospun fiber produced from an isotropic solution imposing planar anchoring along its axis is explored by B-D) homeotropic nematic droplets and E-G) planar nematic droplets.Note the ring defect encircling the fiber in the transmission micrographs B) under parallel polarizers, crossed polarizers with lambda plate and crossed polarizers.The transmission patterns are reproduced in numerical simulations with calculated transmission micrographs under C) crossed polarizers with lambda plate and crossed polarizers, respectively.D) The fiber piercing through the droplet aligns the ring defect perpendicular to the fiber.E-G) In planar nematic droplets, the structure is bipolar-like, with symmetric transmission micrographs.H) A chiral HPC electrospun fibers, imposing chiral in-plane anchoring changes the droplet structure.Note the broken symmetry in homeotropic droplets I-K) and the much brighter fiber in planar droplets L-N).The green and blue ribbons on the fiber in (D), (G), (K), and (N) represent the corresponding surface anchoring direction which is uniform in (D) and (G) and chiral in (K) and (N).The viewing direction is from below the droplets.Reproducedunder the terms of the Creative Commons CC BY license. [113]Copyright 2016, Proc.Natl.Acad.Sci.Copyright 2019, Proc.Natl.Acad.Sci.USA.Reproduced with permission. [116]Copyright 2013, Elsevier B.V.
droplet suspended on the fiber with a less rough surface, a ring defect around the microfilament is visible, which indicates that a tangential anchoring is induced in the liquid crystal along the axis of the microfilament [114] as can be seen in Figure 10.

Gas Sensors
The potential of LCs for the detection of volatile gases was first discovered in 1965 by Fergason who prepared cholesterol-derived compounds to detect hydrochloric acid vapors.Since then, liquid crystal-based sensors have been presented for various gases such as CO2 [115] or NO2. [116]n a typical liquid crystal-based gas sensor, the liquid crystal is supported by a solid surface and is in contact with the atmosphere to be exposed to the volatile compounds to be detected.Upon interaction with gas analytes, a molecular reorganization of the liquid crystal molecules occurs, that induces a director reorientation or a phase transition.This molecular response is generally very rapid, reversible and can be visualized macroscopically, for example using polarized light microscopy.
As an example, nitrogen dioxide (NO 2 ), is a ubiquitous environmental pollutant that is extremely toxic.Prolonged exposure to NO 2 in high concentrations can lead to death.Liquid crystal sensors supported by a gold-coated surface can be produced as this allows for the selective detection of NO 2 .The sensor response depends mainly on the diffusion of NO 2 through the liquid crystal and on its adsorption kinetics on the surface of the gold film.Liquid crystal molecules tend to orient themselves planarly on the gold surface and homeotropically along the interface with the atmosphere.When viewed between crossed polarizers, light passing the first polarizer is partially rotated and manages to pass through the second polarizer, resulting in a clear image.After exposure to an atmosphere containing NO 2 , the NO 2 molecules are adsorbed on the surface of the gold film and as a consequence, the molecules close to the gold surface and close to the interface with the atmosphere, adopt a homeotropic orientation in relation to these surfaces as can be seen in Figure 11.In this way, the light that crosses the first polarizer is extinguished in the second, producing a dark image.
By measuring the rate of change of the optical response at different concentrations, a calibration is possible that leads to the quantitative determination of an unknown concentration. [116]hese sensors are very versatile and selective in detecting the gas for which they were designed, being able to detect concentrations in the order of tenths or hundredths of PPMs.

Bacterial Infection Sensors
Early detection of infectious diseases is critical to the successful treatment and is still the best approach to improving patient survival rates.In particular, the prompt identification of bacteria as infectious agents and their distinction from viruses and fungi is of primary importance for empirical therapeutic decision-making.Liquid crystal bacterial infection sensors have great potential for deployment in developing countries, as well as in situations of bacterial pandemics and epidemics, as a first screening strategy that allows identifying, in a few minutes, potentially infected people among the population.It also has the advantage that, to obtain an optical response, it does not require a power source or an analysis laboratory.
In these sensors, because they can be mounted between two glasses with a transparent conductive oxide on their surfaces, the transduction of the signal can be performed optically (through polarized optical microscopy) [67,84] or electrically (through, for example, measuring the capacity of the cell). [117]Copyright 2020, The authors, published by MDPI.
To carry out the detection, the sensor must be initially empty, or containing an inert solution (to keep the functionalized surface hydrated).Then the liquid to be tested for detection of bacteria, such as water, urine, or saliva, is inserted.If the test liquid contains bacteria, they will be retained on surfaces functionalized for this purpose.Finally, the liquid crystal is injected that will transduce the signal of the presence of bacteria.
The alignment of the liquid crystal molecules in both substrates can be homeotropic or planar, which means that, if not detection occurs and the molecular orientation of the liquid crystal molecule remains unaltered, the light that crosses the first polarizer cannot cross the second (crossed in relation to the first) and, therefore, a dark image will be observed.If the orientation of the liquid crystal molecules is disturbed by the fact that bacteria have been detected and seized, the distortion in the director's field will allow the light passing through the first polarizer to be decomposed into two beams of light, orthogonally linearly polarized, and in this way manage to cross the second polarizer as shown in Figure 12.This light, when crossing the second polarizer, gives rise to a clear image or a characteristic texture. [118]

DNA Sensors
In biological studies, its important the selective and sensitive detection of nucleic acids. [119]One of the liquid crystal DNA sensing limitations is the small amounts of which DNA sequences of interest may exist.This fact might be easily overcome, if signal amplification techniques that allow for the detection of trace levels of a specific sequence is implemented.
The usage of Gold NanoParticles (AuNPs) is one of the signal amplification techniques that has been successfully employed in liquid crystal DNA sensors.AuNPs are easily synthetized, present a large specific surface area, are chemically stable, biocompatible, and have a high affinity to bind to amine/thiol-containing molecules. [120]Taking into account that these LC sensors working mechanism is based on the director field distortion, AuNPs having a large specific surface area, capable of accommodating a considerable number of DNA strands on its surface, increases the disruption to the LC orientation, upon DNA of interest detection. [121]he sensor architecture is similar to the ones described before, the inner surface of the glass slides are chemically functionalized with (3-aminopropyl)trimethoxysilane (APS)/N,N-dimethyl-N-octadecyl-3-aminopropyltrimethoxysilyl chloride (DMOAP) in order to allow the attachment of the AuNPs (that will bind to the DNA stands) while inducing an homeotropic alignment on the LC molecules, after the sensor is filled with LC.When no DNA strands of interest are bind to the AuNPs (negative result), between cross polarizers, a dark optical image is obtained, since no considerable distortion is imposed to the LC director field.In the case of detection of DNA, the mean orientation of the LC molecules is distorted and between cross-polarizers, a bright optical image is obtained, denoting a positive result for the presence of DNA strands of interest. [121]An example of the working mechanism of these sensors can be seen in Figure 13.

Cancer Cells Sensors
The geometry of the LC sensors is diverse.As mentioned before, droplets might be used as sensing elements.When the chirality or morphology sensors where abovementioned, those droplets were suspended in air, threaded by a fiber.Another architecture that might be used in biological systems sensing with liquid crystals, is the liquid crystal droplets dispersion.LC microdroplets emulsions have attracted a significant interest for the detection of chemicals or biomolecules in biological systems.Depending on the composition of the outer interface of the droplet, one can induce a homeotropic or a planar alignment in the LC molecules .Reproduced with permission. [122]opyright 2015, Elsevier B.V. inside the droplet.If the molecules are aligned homeotropically (perpendicular) with respect to the droplet surface, they present a radial (R) conformation, if the molecules are aligned planarly (parallel) with respect to the droplet surface, they present a bipolar (B) conformation.Exterior compounds such as cells, when attached to a receptor, are able to modify the conformation of the LC molecules from radial to bipolar.
Using folic acid-conjugated polystyrene and sodium dodecyl sulfate as a mediator to induce high selectivity and sensitivity, a nematic liquid crystal microdroplet emulsion may be produced.Since KB cancer cells interact with the liquid crystal droplets because of the presence of a cancer cell folate receptor-specific ligand from KB, it is possible to detect the presence of cancer cells in the test medium. [123]pon detection, the presence of cancer cells induces a modification of the orientation of the liquid crystal molecules with respect to the outer surface, from homeotropic to planar as can be visualized in Figure 14.When observed between cross polarizers, the observed texture is diverse if the molecules inside the droplets have a homeotropic or a planar anchoring.Being so, the texture observed between cross polarizers when no cancer cell is detected is the typical texture presented by a radial droplet, and the texture observed between cross polarizers when cancer cells are detected is the typical texture presented by a bipolar droplet.
There is a myriad of compounds and entities that LC sensors can sense and being applied to medicine and public health besides the ones that were mentioned, such as glucose, [124] cholesterol, [125] heavy metals, [126] enzymes, [127] urease, [128] etc.The working mechanism of all of them is similar to the ones above mentioned.Reproduced with permission. [123]Copyright 2014, American Chemical Society.

Highlights of Nanomaterials Functionalization
Functionalization consists of surface modification, improving the properties and characteristics of nanomaterials.Several strategies can be used in order to functionalize nanomaterials, through chemisorption and physisorption, electrostatic interactions, covalent interactions using conjugation chemistry, noncovalent or supramolecular affinity, or intrinsic surface engineering. [128]Regarding covalent interactions, nanomaterials usually present chemical properties and functional groups on their surface that can be used in conjugation with the first step of functionalization. [129]For the first step of the functionalization, several different chemical approaches can be used, in which homo-or hetero-bifunctional cross-linkers are applied in order to immobilize an organic functional group to allow the binding of biological molecules.[130] This and the other approaches are described in detail. [128]Recently, biofunctionalization, another type of functionalization, has started to be used due to its great biocompatibility, eco friendliness, low cost, and biodegradability.To perform this type of functionalization is used bioinspired ligands, natural phytochemicals, and natural bioresources for example plants, algae, bacteria, microorganisms, among others. [130]n this way, nanomaterials functionalization of LC sensors can be achieved to obtain new perspectives in different areas of applications in order to guarantee selectivity, robustness and reliability.

Conclusions
This paper presented a review of LC sensors applications in healthcare and human life quality.The overview of the sensors applications and demands for the improvement of life quality is presented and discussed, where the main technologies for multiparameter assessment are discussed.In this case, the advantages of the LC sensors are also depicted as an important tool for intuitive and sustainable sensors approaches.Then, the fabrication methods, operation principle, and HPC membranes functionalization are discussed.Thereafter, the sensors applications of the LCs/CLCs are discussed in a myriad of parameters, ranging from strain sensing to DNA and chirality assessment.Therefore, the use of LC sensors in different applications provides important advantages and can be regarded as an important prospect for a myriad of applications.In this context, one can envisage a widespread of such technologies due to advantages such as low cost, flexibility in fabrication, simple signal processing, biocompatibility, and biodegradability.For these reasons, it is possible to infer a matrix of Strengths, Weakness, Opportunities and Threats (SWOT) for the LC sensors based on HPC membranes.Figure 15 presents the SWOT matrix of LC sensors for healthcare and human quality of life applications, where it is possible to observe the strengths of the sensor system related to their low cost, easy fabrication, sustainability, and flexibility on fabrication.Such strengths lead to opportunities on the widespread of such sensing technology related to new regulations of the use of green technologies, new techniques of LC sensors fabrication, innovations in signal processing and computer vision for color identification as well as the possibility of different functionalization methods for additional applications of these sensors.However, there is also the necessity of overcome the weakness of the LC sensors technologies, which include the challenges on the shape customization, the challenges on large-scale fabrication of the sensors and the dependency of reflected wavelength as a function of the reflected angle.Thus, the threats related to LC sensors widespread are related to the regulations and standards of LC sensors as well as the accuracy in the sensor responses (which is critical for some applications) and the inevitable competition with many other sensing technologies.
The future developments in LC sensors applications are related to the mitigation of the weakness of such sensors, which can be achieved with different fabrication methods as well as the integration and doping with different materials.As the drawbacks of this sensor technologies are mitigated, there is a vast green field for LC sensors in a multitude of applications that can be an important topic in the next few years.Considering the future applications of the devices, there is not only the biomedical ones discussed in this paper, but also the structural health monitoring, which can be used in aircrafts internal components assessment.In addition, there is the possibility of monitoring crew members by smart sensors using the combination of LC and plasmonic structures [74,131] as well as the operational conditions inside an aircraft cabin.It is important to mention that the flexibility in fabrication in conjunction with the biodegradability of the proposed device enable its application on the aerospace applications with the use of the sensor for the tactile systems in the cabin, where the proposed device can be integrated in the liquid crystal touch screens.

Figure 1 .
Figure 1.Overview of plasmonic sensing technologies.a) LSPR sensor chip coated Au NPs layer.Reproduced with permission.[58]Copyright 2023, Springer.b) Representation of the grating-based fiber optic SPR sensor, in which D is the fiber core diameter, L is the sensing region length, d is the grating period, and d1 is the groove width.Reproduced with permission.[59]Copyright 2020, Elsevier.c) Schematic representation of SPR aptamerbased insulin sensor in a four-channel microfluidic format.Reproduced with permission.[60]Copyright 2020, Elsevier.d) Schematic representation of T4 detection using anti-T4/C-AuNPs nanoprobe.Reproduced with permission.[61]Copyright 2020, ACS.e) Schematic representation of EE2 detection using cellulose fiber yarns modified with cyclodextrins.Reproduced with permission.[62]Copyright 2018, ACS.

Figure 2 .
Figure 2. Overview of the sensors applications on the human quality of life.

Figure 5 .
Figure5.Formation of a cholesteric helical structure by doping nematic liquid crystals with chiral molecules.Blue rods present LC molecules.n is LC director indicating molecular orientation.Helix pitch (P) corresponds the distance over which director makes a full rotation of 360°.Reproduced with permission,[97] Copyright 2022, John Wiley and Sons.

Figure 8 .
Figure 8. a) Photographs of the CLC/PVA/glycerol/water mixture before (left) and after (right) emulsification.b) Image of the emulsified Polymer Dispersed CLC (PDCLC) coating upon body contact, visualizing local temperature distributions.c) Temperature-responsive reflection band shift of a 25 μm thick PDCLC coating.d) Reflection band spectra at T = 32 °C for PDCLC coatings having thicknesses of 8, 19, and 25 μm.e) POM images of a 25 μm thick PDCLC coating showing thermally induced color tuning inside the CLC droplets.The scale bar corresponds to 100 μm.f) Enlargement of the POM image in (e) visualizing the photonic cross-communication between the CLC droplets.The scale bar corresponds to 25 μm.Reproduced with permission.[109]Copyright 2022, John Wiley and Sons.

Figure 10 .
Figure10.Tracheary microfilament morphologies revealed by nematic liquid crystal droplets.A1-G1) A. africanus and A2-G2) O. thyrsoides microfilaments.A1 and A2 show SEM images of a detail of a stretched filament in which an elbow is seen.The roughness is highlighted by a white circle.The filament from A. africanus A1) presents a rough surface, and the filament from O. thyrsoides A2) presents a smoother one.B1 and B2 show a necklace of nematic droplets suspended along a microfilament, seen by POM under cross polarizers.C1, C2, D1, and D2 show a nematic droplet with homeotropic anchoring at the droplet-air surface under crossed polarizers with a lambda plate and crossed polarizers pierced in A. africanus and O. thyrsoides tracheary microfilaments.E1, E2, F1, and F2 show numerically simulated transmission micrographs under crossed polarizers with an additional lambda plate and crossed polarizers for droplets pierced in A. africanus (E1 and F1) and O. thyrsoides (E2 and F2) tracheary microfilaments.Simulated director profile in droplet suspended in an A. africanus (G1) and in an O. thyrsoides (G2) tracheary filament.Ellipsoidal fringes, typical of homeotropic anchoring on the microfilament surface, can be observed in the nematic droplets pierced in A. africanus tracheary microfilaments, while the defect ring around the microfilaments for droplets pierced in O. thyrsoides tracheary microfilaments reveals that the microfilament enforces tangential anchoring along the microfilament's axis.(Scale bars: A1 and A2, 2 μm; B1 and B2, 20 μm; and C1, C2, D1, and D2, 10 μm.) Reproduced under the terms of the Creative Commons CC BY license.[114]Copyright 2019, Proc.Natl.Acad.Sci.USA.

Figure 11 .
Figure 11.Left -Principle of real-time detection of NO2: a) Organization of LC molecules within a thin film of LC supported on a gold coated substrate.b) The sensor appears bright when viewed between crossed polarizers.c) A subtle change in the structure of the interface (i.e., binding of NO 2 at the gold-LC interface) is amplified into a change in the orientation of the LC and d) the sensor appears dark when viewed between crossed polarizers.Right -Selective detection of NO2 using LC-based sensors: Identical sensors optimized for detection of NO 2 were exposed to 5 ppm NO 2 and vapors from common atmospheric chemicals at very high concentrations.The sensors respond to NO 2 while remaining immune to exposure to other chemicals for much longer than 200s depicted in the figure.The dotted triangle shows the segment of the response curve used for measurement of the response rate.Reproduced with permission.[116]Copyright 2013, Elsevier B.V.

Figure 12 .
Figure 12.Diagram of the LC-solid interface sensing principle.Reproduced under the terms of the Creative Commons CC BY license.[118]Copyright 2020, The authors, published by MDPI.

Figure 13 .
Figure 13.Principles for detection of DNA by using LC.Red probes represent DNA whereas blue probes represent PNA.A) DNA contact with sodium ion.B) DNA contact without sodium ion.C) PNA contact with sodium ion.D) PNA/DNA complex contact with sodium ion.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article).Reproduced with permission.[122]Copyright 2015, Elsevier B.V.

Figure 15 .
Figure 15.SWOT matrix LC sensors based on HPC membranes.