Intelligent point of care testing for medicine diagnosis

Intelligent point‐of‐care testing (iPOCT) is a rapidly advancing technology that combines molecular detection and bio‐sensing techniques to achieve instant and accurate analysis through advanced sensors and intelligent algorithms. Molecular detection technologies, such as nucleic acid isothermal amplification, biochip and microfluidics, enable rapid analysis of the chemical composition and concentration of samples, thereby determining their presence. Bio‐sensing technology utilizes the recognition properties of biomolecules in conjunction with sensors to detect specific biomolecules or biological processes. iPOCT technology holds broad prospects for application in the field of healthcare and is expected to enhance detection sensitivity, accuracy, and intelligence through further development. In this review, we delineate the developmental journey of iPOCT, followed by a discussion on the principles of molecular detection and bio‐sensing technology, as well as the design of iPOCT devices for health monitoring and disease diagnosis. Furthermore, we showcased illustrative examples of iPOCT applications in disease diagnosis, highlighting the integration of iPOCT technology with wearable devices and smartphones for attaining more precise and personalized diagnostic results.


| INTRODUCTION
Point-of-Care Testing (POCT) is one of the fastest growing and emerging fields in laboratory medicine.The definition of POCT was given by The National Academy of Clinical Biochemistry (NACB) in 2007 in the publication of the Evidence-Based Practice for Point-of-Care Testing: clinical laboratory testing conducted close to the site of patient care, typically by clinical personnel whose primary training is not in the clinical laboratory sciences or by patients (self-testing). 1,2POCT utilizes portable analytical instruments and corresponding reagents to perform onsite testing, providing rapid results.Compared to traditional methods that involve sample collection, storage, and transportation to central laboratories for analysis, POCT reduces delays and enables earlier disease diagnoses.One of the advantages of POCT is its ability to be performed in multiple locations.Healthcare professionals can conveniently access real-time test results, enabling more accurate diagnoses and treatment decisions.Additionally, patients can engage in flexible self-monitoring, empowering them to better understand and manage their conditions.Due to its rapid analysis and easy operation, POCT has been widely adopted in various fields such as medical care, [3][4][5] environmental monitoring 6,7 and food safety. 8,9he paradigm shift in modern medical practices has steered hospitals from mere therapeutic endeavors toward comprehensive, systematized healthcare systems encompassing prevention, wellness, treatment, and rehabilitation, thereby furnishing society with all-encompassing, high-quality services.The advent of POCT not only aligns with the fast-paced, efficiency-centric ethos of contemporary society, but also empowers patients with prompt diagnosis and treatment, particularly in resourceconstrained or decentralized settings. 10round 1500 AD, some physicians observed that ants exhibited a strong attraction to the urine of patients suffering from a condition known as "diabetes mellitus".This led them to speculate that the urine of such patients may contain sugars, prompting further investigations.This discovery is considered as one of the earliest applications of POCT, providing doctors with a simple yet effective method to detect diabetes.The origins of modern POCT can be traced back to the mid-20th century.Edmonds was the first to employ dried chemical reagent strips for the detection of blood and urine glucose, laying the foundation for subsequent POCT technologies.Ames Corporation later expanded and commercialized the use of dried chemical reagent strips, further driving the development of POCT.Over time, an increasing number of POCT methods have been developed and implemented. 113][14] These methods have found widespread application in clinical healthcare settings and have been warmly embraced by patients, clinicians, and laboratory professionals alike.
Up to date, the evolution of POCT products has undergone four generations of transformative advancements (Figure 1).These transformations have brought significant improvements and innovations in terms of technology and functionality.The first generation of POCT products primarily relied on visual observation of color changes in test strips or the presence or absence of control/test lines to determine positive or negative results.6][17] However, the first-generation products lacked quantitative values, and the subjectivity of manual visual interpretation could impact the accuracy of results, thus limiting their use in the professional healthcare market.The secondgeneration POCT products relied mainly on card-based colorimetry or instruments for semi-quantitative testing.Examples of such products include urea colorimetric cards and blood glucose test strips. 18,19Compared to the The development history of POCT from the first generation to the fourth generation.

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-GAO and LI first generation, the second generation of POCT products is more accurate and reliable, providing a certain level of numerical results.The third-generation POCT products require minimal manual operation and have full quantitative capabilities.Examples of these include handheld blood glucose monitoring devices, portable in-body and out-body monitoring devices, as well as compact desktop testing equipment.These devices are user-friendly, provide specific numerical results, and are suitable for a wider range of clinical applications and settings. 8,20The fourth generation of POCT products has evolved into a technological platform that integrates automation, informatization, and intelligence.These devices are capable of fully automated sample pre-processing, data analysis, and data transmission.Through automated processes, the accuracy and efficiency of diagnostics are improved.Realtime data transmission and analysis are also achieved, facilitating decision-making and management for healthcare professionals. 21,22With continuous technological advancements, future POCT products are expected to further develop, offering faster, more accurate, and convenient diagnostic and monitoring services, leading to significant improvements and advancements in clinical healthcare.
The stage of POCT development characterized by precision, automation, and cloud integration is referred to as intelligent point-of-care testing (iPOCT).][25] It aims to provide rapid and real-time testing results in clinical or other application scenarios by utilizing miniaturized and portable devices.iPOCT devices are typically equipped with various sensors that can be used to detect various molecules, substances, or biological markers in biological samples.The data collected by the sensors are transmitted to the device processing unit, where they are processed and interpreted using data analysis and machine learning algorithms.Such technological solutions enable iPOCT to provide accurate diagnostic results and, if necessary, offer corresponding treatment recommendations.As an integral part of the in vitro diagnostics (IVD) industry, iPOCT embodies the innovative traits of Internet thinking and has become a crucial avenue for achieving precision medicine.One of the key characteristics of iPOCT is its precision.It relies on advanced artificial intelligence technologies and algorithms to process and analyze vast amounts of data, enabling pattern recognition and prediction through machine learning algorithms.It can provide personalized diagnostic recommendations based on a patient's condition and historical data, enhancing the accuracy and efficiency of medical decision-making.This precision contributes to disease prevention, early detection, and precise treatment.Moreover, iPOCT achieves efficient and rapid sample handling and analysis through automated instruments and devices.With technological advancements, sensors and detection devices have become increasingly compact, lightweight, and capable of delivering higher accuracy and sensitivity.Intelligent POCT devices are capable of providing real-time results within minutes, enabling fast and convenient testing.By reducing manual operations and interventions, iPOCT minimizes operational errors and result uncertainties, while saving healthcare professionals time and labor costs.Furthermore, iPOCT devices have the capability to integrate test results with a patient's clinical data, providing comprehensive diagnostic information to healthcare professionals through data analysis and cloud computing technologies. 26This integrated analysis approach assists doctors in accessing test results anytime and anywhere, enabling rapid assessment of disease risks, guiding treatment decisions, and facilitating remote collaboration and monitoring.Cloud-based infrastructure promotes the application of big data by aggregating and analyzing multiple test results, providing richer data resources for disease research and prediction.
This review highlights the significant advancements in iPOCT technologies in recent years and explores their potential as non-invasive precision medical devices.The review provides a detailed overview of the fundamental principles of iPOCT systems, including molecular detection techniques and bio-sensing technologies (Table 1).It further presents examples of iPOCT applications in common disease diagnoses, outlining the overall importance and future prospects of iPOCT devices in the field of biomedical research.The discussed studies predominantly involve iPOCT devices based on biochips, microfluidics, and electrochemical signal transductions, as these disease diagnostic mechanisms have been most frequently reported in recent years.The review emphasized the need for system integration tailored to real healthcare applications, with the hope of achieving clinical translation in the near future.The development of iPOCT technology offers new possibilities for noninvasive, rapid, and accurate health monitoring and disease diagnosis.

TECHNOLOGY
Molecular detection technology is a method used to detect the molecular structure, existence, concentration and purity of analytical substances.With advancements in technology, molecular detection techniques have found wide applications in fields such as biology, GAO and LI T A B L E 1 Summary table, including the type of technology introduced in the review, the principle of the technology, application examples of the technology, and the target analytes of the applications.

Technology types Technical principles Application examples Analytes
Moleculer detection ITA Amplifying nucleic acid fragments under constant temperature conditions.
Colorimetric isothermal sensing platform 27 DNA/RNA Target DNA fluorescent and colorimetric detection 28 DNA Nanoplasmonic enhanced isothermal amplification 29

RNA
The lateral flow immunoassay strip-based detection   [67][68][69][70][71][72] Advancements in molecular detection technologies have facilitated their integration with chipbased platforms, leading to the development of iPOCT devices.This groundbreaking innovation has enabled more precise and personalized clinical diagnostics and treatments, thereby significantly improving patient survival rates and quality of life.These advancements have revolutionized the field of molecular diagnostics, empowering healthcare professionals with valuable tools to make informed decisions and tailor treatments to individual patients.

| Nucleic acid isothermal amplification
Nucleic acid amplification is a crucial process in biological systems.Polymerase chain reaction (PCR) is the first and most widely used technique for amplifying and detecting low-abundance nucleic acids.Despite its extensive applications across various fields, PCR requires large and expensive thermal cyclers, which greatly limits its use in resource-limited environments and iPOCT applications.4][75] This A sensitive iPOCT platform for the digital quantification 54 Uric acid in salivary An innovative non-invasive eyemask wearable biosensor 55 pH, proteins, ascorbic acid, and glucose of human tears A biomimetic microneedle therapy platform 56 Glucose and physiological ions GAO and LI makes ITA more suitable for modern iPOCT, where simplicity and portability are key considerations.ITA has found wide applications in fields such as molecular biology, medical diagnostics, and environmental monitoring, presenting numerous advantages. 76,77It enables rapid and accurate detection of pathogenic nucleic acids, including viruses, bacteria, and fungi, making it crucial for early diagnosis of infectious diseases and epidemic surveillance. 78,79Additionally, ITA can be used for detecting gene mutations and genetic disorders, providing important support for personalized medicine. 80,81ommon ITA techniques include Loop-mediated isothermal amplification (LAMP), Recombinase Polymerase Amplification (RPA), Strand Displacement Amplification (SDA), and helicase-dependent amplification (HDA), each with its own characteristics and applicable range.The choice of a specific ITA method depends on the experimental requirements and the target of detection.Furthermore, there are emerging nucleic acid isothermal amplification technologies, such as Hotspot Auto-nucleic acid Detection (HAD) and Nucleic Acid Sequence-based Amplification (NASBA), which hold potential applications in various fields.
LAMP was a technology introduced by Notomi et al. in 2000 that allowed for the specific amplification of nucleic acid fragments under isothermal conditions. 82AMP has gained widespread applications in the fields of molecular biology, medical diagnostics, and more, owing to its high specificity, sensitivity, and rapid amplification speed.LAMP utilizes a special DNA polymerase, typically Bst polymerase, along with multiple primers to achieve the amplification of specific nucleic acid sequences through steps such as priming, strand displacement, and annealing.The primers used in LAMP primarily consist of two specific primers (F3 and B3) and two loop structure primers (FIP and BIP). 83Together, they form a complex DNA structure with multiple reverse and forward loops, enabling highly specific amplification.
HDA is a high-specificity and high-efficiency ITA technology.In 2004, Vincent et al. designed HDA to simulate DNA replication. 84It utilizes enzymes such as DNA helicase and DNA polymerase to amplify target DNA sequences under constant temperature.The basic principle of HDA involves the unwinding of DNA double strands by DNA helicase, resulting in the formation of two single-stranded DNA molecules.One of these singlestranded DNA molecules acts as a primer, binding to the corresponding region of the target sequence.The DNA helicase, through its interaction with the primer binding site, facilitates the binding of another primer to the other end of the target sequence.Subsequently, DNA polymerase initiates the synthesis of a new DNA chain starting from the primer binding site.In this way, the target DNA sequence undergoes amplification.The entire process takes place under isothermal conditions, without the need for complex temperature cycling equipment.
RPA is an isothermal amplification strategy first proposed by Piepenburg et al. in 2006. 85RPA utilizes recombinase enzymes, DNA polymerase, and primers to initiate the amplification of target nucleic acid sequences under isothermal conditions.The primers used in RPA consist of two outer primers and two inner primers, which specifically bind to the target sequence, forming DNA/RNA complexes that facilitate recombination and amplification events.RPA reactions are typically conducted at temperatures ranging from 37 to 42 degrees Celsius, allowing for amplification under standard laboratory conditions without the need for complex temperature cycling equipment.RPA enables rapid amplification of target nucleic acid segments within a short time frame, typically between 10 and 30 min.
SDA was first proposed by Walker and Fraiser in 1992, 86 and it achieves specific nucleic acid amplification under isothermal conditions using a unique molecular recognition system that combines specialized polymerases with restriction enzymes.The key steps of SDA amplification involve two main reactions: the first is the homologous recombination reaction, in which the DNA or RNA template binds to a non-complementary "primer" polymerase complex and introduces the amplification sequence into the template through homologous recombination.The second step is the DNA polymerase amplification reaction, in which the lowtemperature denaturation of the primer allows DNA polymerase to bind and synthesize new DNA strands.By cycling through these two reaction steps, the target nucleic acid sequence can be specifically amplified under isothermal conditions.Specific primers and restriction enzyme recognition sequences are used in the SDA amplification reaction, enabling highly specific amplification of the target nucleic acid while avoiding nonspecific amplification.
The application of ITA in IVD and iPOCT has been hindered by the lack of a mature specific signal output mechanism.He et al. designed a visual signal reporting system to filter and amplify target information during isothermal amplification (Figure 2A). 27They developed a colorimetric isothermal sensing platform with a specific signal filtering and amplification for ultrasensitive detection of DNA and RNA.The platform consists of two processes: an isothermal amplification process with a specific signal filtering and a self-replicating catalytic hairpin assembly process for rapid target-specific signal amplification and export.Thanks to the excellent colorimetric detection performance, this biosensing platform has been successfully used for the detection of African swine fever virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gamma.In 2023, He et al. developed a specific signal extraction and output isothermal detection system to address this challenge (Figure 2B). 28The system comprises a DNA probe designed for the extraction and output of specific signals from LAMP.This probe, referred to as an extraction-output probe, is a double-stranded DNA with a dangling sequence capable of recognizing targetspecific intermediates in LAMP and releasing another signal output probe to report the target-specific signal.Leveraging these unique features, this system enables the detection of target DNA as low as 10 copies per reaction, either by fluorescence detection or by the naked eye.Furthermore, this biosensing platform exhibits excellent resistance against background nucleic acid interference and has been successfully applied in the clinical detection of hepatitis B virus samples.
The prevention and treatment of viral respiratory diseases pose significant challenges due to their wideranging transmission and high viral variability.The development of rapid iPOCT devices is crucial for the large-scale containment of diseases in public settings and resource-limited remote areas.Liu's group has developed a strategy called nanoplasmonic enhanced isothermal amplification (NanoPEIA), which combines nanoplasmonic sensors with isothermal amplification (Figure 2C). 29This approach provides an ideal and userfriendly POCT detection platform for obtaining accurate, ultra-fast, and high-throughput data.For clinical samples with a Ct value of <25 in viral detection, the entire process, including sample preparation, viral lysis, detection, and data analysis, can be completed within 6 min.This method is also applicable for detecting mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gamma and other coronaviruses causing severe acute respiratory syndrome.Zou et al. designed an accurate, rapid, and easy-toimplement isothermal and non-enzymatic signal amplification system combined with a lateral flow immunoassay strip-based detection method, capable of detecting SARS-CoV-2 in oropharyngeal swab samples (Figure 2D). 30This approach circumvents the need for RNA isolation, PCR amplification, and complex result analysis, thereby shortening the detection time.The method is simple, requiring only a simple water bath for isothermal control and a fluorescence reader, without the need of expensive equipment.
of the colorimetric isothermal sensing platform.Reproduced with permission. 27Copyright 2022, Elsevier.(B) Principle of the signal extraction and output isothermal detection system and its application for target DNA fluorescent and colorimetric detection.Reproduced with permission. 28Copyright 2022, Elsevier.(C) Schematic of high throughput and point-of-care testing of NanoPEIA for SARS-CoV-2.Reproduced with permission. 29Copyright 2022, Elsevier.(D) Overview of the lateral flow immunoassay strip-based detection method for SARS-CoV-2 viral RNA detection.Reproduced with permission. 30Copyright 2021, Elsevier.

| Microfluidics
Microfluidics is a revolutionary technology involving the manipulation of minute fluid volumes through microscale channels and devices, enabling precise control and handling of small samples. 87It originated in the 1990s, when researchers became interested in microscopic fluid behavior and explored ways to control and manipulate fluids at the microscale. 88The advent of microfluidic technology has brought about a significant shift in the way liquids are processed and analyzed, offering advantages such as high efficiency, rapidity, sample conservation, and flexibility.The principles and implementation of microfluidics are rooted in the characteristics and behaviors of fluids at the micrometer scale.Microscale devices such as micropipes, microvalves, and micropumps are employed to regulate and manipulate the flow and transport of microfluids.By designing and tuning the structures, geometries, and surface properties of microchannels, operations such as fluid separation, mixing, analysis, and reaction can be achieved.Additionally, microfluidics can be combined with techniques such as optics, electrochemistry, and biosensors to enable high sensitivity and high-throughput analysis and detection.
Microfluidics finds wide-ranging applications in numerous fields.In the field of life sciences, microfluidic technology has found applications in cell analysis, gene expression profiling, protein research, and cell signaling, among others.3][94] Microfluidic technology offers several advantages across various aspects.Firstly, it enables efficient mixing, analysis, and reactions of samples, thereby enhancing experimental efficiency and speed.Secondly, microfluidics is characterized by its sample and reagent conservation, allowing analyses to be performed with minute sample volumes and reducing waste and costs.Additionally, microfluidic technology enables highthroughput and automated operations, catering to the demands of large-scale and high-throughput experiments.Lastly, the microscale dimensions and microgravity environment associated with microfluidics confer unique advantages and application value in the study of cells and microorganisms.
Microfluidics enables continuous liquid handling and parallel reaction operations.Microfluidic-based multiplexed iPOCT devices, when combined with molecular detection technologies, have the potential to revolutionize clinical diagnostics.In 2023, Zhou et al. reported a heated membrane-assisted multiplex microfluidic platform that combines RPA and CRISPR technologies for rapid and cost-effective detection of multiple HPV subtypes (Figure 3A). 31The heated membrane facilitates temperature control for RPA and CRISPR detection on the chip.This system allows simultaneous detection of HPV16 and HPV18 within 30 min, demonstrating high specificity and detection sensitivity, with fluorescence-based readout capability.Furthermore, an optimized lateral flow strip was introduced in a portable system for visual detection of HPV DNA, and successful detection of HPV subtypes in clinical samples was achieved.The final integrated microfluidic system enables sample-to-answer detection of HPV subtypes in an automated manner.In 2020, Ganguli et al. developed a simple microfluidic iPOCT device for detecting SARS-CoV-2 using the reverse transcription LAMP method (Figure 3B). 32This device utilizes a separately manufactured three-dimensional reagent box and an optical reader based on a smartphone for virus detection from viral samples.It eliminates the need for additional external devices for sample/reagent mixing, amplification, or readout.In 2023, Kshirsagar et al. presented a novel handheld nucleic acid detection device with integrated onchip sample preparation for the detection of Plasmodium falciparum, the causative agent of severe malaria, from whole blood samples (Figure 3C). 33This technology employs a simple purification-free approach, utilizing two reagents for the preparation of whole blood samples on a microfluidic cartridge driven by a piezoelectric pump.By utilizing this device, accurate detection of asymptomatic malaria carriers is enabled.
Microfluidic chips have made significant breakthroughs in miniaturization and integration, emerging as a highly promising platform.However, traditional microfluidic chips continue to face challenges in terms of manufacturing difficulties, extended production times, and high costs.These drawbacks impede their applications in the fields of iPOCT and IVD.Li et al. have developed a capillary-based microfluidic chip, characterized by its low cost and ease of fabrication, for rapid detection of acute myocardial infarction. 34The chip consists of two working capillaries encapsulated within a plastic housing, one for calibration of the standard curve and the other for quantitation of the samples (Figure 3D).These working capillaries are composed of several short capillaries, each selectively functionalized with different capture antibodies on their inner surfaces and connected through peristaltic pump tubing.This capillary-based microfluidic chip reduces the requirements, time, and costs associated with a microfluidic chip fabrication, while importantly enabling simultaneous detection of multiple biomarkers.
Compared to traditional microfluidic approaches, modular microfluidics offers a promising solution for industrial-scale production by significantly reducing manufacturing costs through the production of individual chips.In a departure from previous studies that involved the combination of multiple microfluidic chips in modular designs, Lai et al. have introduced a novel "template-sticker" approach (Figure 3E). 95This method enables the batch production of sacrificial templates for microfluidic components in a standardized adhesive format, which are then connected and packaged in a toolbox using emulsion-based guided wetting.By simply arranging stickers and casting an elastomer, a singlepiece microfluidic device can be directly obtained.Endusers can create their target microfluidic systems by selecting and combining various template stickers following a prescribed set of steps.The resulting microfluidic devices are compact in size and possess the ability to create microchannels on curved surfaces, in addition to being cost-effective and time-efficient to manufacture.Serving as an independent and portable platform, the sticker toolbox represents the first of its kind for microfluidic fabrication.It enables rapid customization of single-piece devices, allowing for the creation of highly specialized microfluidics with minimal requirements.

| Biochip
In recent years, biochips have garnered extensive attention and research as rapid, efficient, and multifunctional tools for biological analysis.Integrated with microelectronics, biology, and sensor technologies, biochips enable the simultaneous execution of various biological experiments on a miniature chip.They hold immense potential and promising applications in the field of bioanalysis.Biochips can be broadly classified into two categories: gene analysis chips and protein analysis chips.Gene chips are primarily used for studying gene expression and mutations, offering advantages such as high throughput, sensitivity, and selectivity.They can simultaneously detect thousands of genes, playing a crucial role in researching gene function and diagnosing genetic diseases. 96,97On the other hand, protein chips are employed for studying protein structure, function, and interactions. 98,99They enable highthroughput screening of drug targets, disease diagnosis, and monitoring biological processes.The fabrication techniques for biochips are constantly evolving and innovating.Currently, commonly used methods include photolithography, microfluidics, inkjet printing, and electrochemical deposition.These techniques have made the fabrication of biochips more convenient and scalable, F I G U R E 3 (A) Scheme of the CRISPR detection platform.Reproduced with permission. 31Copyright 2023, American Chemical Society.(B) Workflow for the detection of SARS-CoV-2 using the portable POC device.Reproduced with permission. 32Copyright 2020, National Academy of Sciences.(C) Schematic diagram of the structure of a handheld purification free nucleic acid detector.Reproduced with permission. 33Copyright 2023, American Chemical Society.(D) The design of the capillary-based microfluidic chip.Reproduced with permission. 34Copyright 2023, Elsevier.(E) Schematic diagram of the Sticker Toolbox for microfluidic customization.Reproduced with permission. 95Copyright 2019, American Chemical Society.
reducing production costs, and improving chip stability and repeatability.
The applications of biochips are exceptionally diverse.In basic scientific researches, biochips are used for gene expression analysis, protein interaction studies, cellular signaling, and more.In the field of medical diagnostics, biochips can be employed for early disease detection, personalized medicine, drug screening, and beyond.In environmental monitoring and food safety, biochips find utility in water quality analysis, pesticide residue detection, screening for harmful substances in food, and other applications.The advantages of biochips primarily lie in their high throughput, speed, and low sample consumption.They have the capability to process multiple samples simultaneously, enabling high-throughput analysis, thus saving time and resources.Furthermore, biochips have low sample consumption and are capable of performing analyses at the microscale and single-cell level, contributing to the goals of personalized medicine and precision healthcare.
Biochip technology holds great potential for the detection and investigation of tumor biomarkers, facilitating early screening and diagnosis of tumors, as well as guiding individualized treatments.Yang et al. developed an immunobiomarker biochip targeting tumor-associated proteins (Figure 4A). 35This biochip utilizes surfaceimmobilized tumor-associated protein biomarkerspecific antibodies to enrich tumor-derived exosomes, followed by quantitative detection of exosomal RNA using cationic lipid complexes incorporating molecular beacons.The immunochip significantly enhances the sensitivity and specificity of detection, exhibiting superior diagnostic performance in lung cancer, while reducing the detection time from approximately 24-4 h.Singh F I G U R E 4 (A) Schematics of detection procedures of immuno-biochip.Reproduced with permission. 35Copyright 2018, American Chemical Society.(B) Schematic representation of the fabrication of microfluidic biochip for detection of Cardiac biomarker.Reproduced with permission. 36Copyright 2017, American Chemical Society.(C) Schematic illustration of time-gated detection by the developed biochip.Reproduced with permission. 37Copyright 2019, American Chemical Society.(D) Schematic illustration of the photonic crystalassisted RCA biochip.Reproduced with permission. 38Copyright 2018, American Chemical Society.(E) Schematic diagram of biochip design and usage process.Reproduced with permission. 100Copyright 2018, American Chemical Society.4B). 36This biochip employs a modified porous manganese oxide reduced graphene oxide (Mn 3 O 4 -RGO) nanocomposite integrated with a polydimethylsiloxane-based microfluidic system, along with functionalized microelectrodes using cardiac troponin I-specific antibodies.The integration of Mn 3 O 4 -RGO nanocomposite with microfluidics provides a promising microfluidic biochip platform for iPOCT of cardiac troponin.Wang et al. have developed a photonic crystal (PC)-supported time-gated luminescent probe biochip for the detection of miRNA biomarkers related to bladder cancer in urine samples, demonstrating high sensitivity and specificity (Figure 4C). 37This biochip exhibits outstanding performance in urine miRNA detection, showcasing unique ultra-low background and luminescent enhancement properties, providing a suitable tool for the detection of bladder cancer-related miRNA in urine.Yao et al. similarly engineered an ultra-sensitive photonic crystal-assisted rolling circle amplification (RCA) biochip for the detection of miRNA in serum (Figure 4D). 38This biochip integrates the light signal-enhancing capability of the biomimetic photonic crystal surface with the thousandfold signal amplification characteristic of RCA.The biomimetic photonic crystal exhibits periodic dielectric nanostructures, significantly enhancing the signal intensity of the RCA reaction, thereby effectively improving the detection sensitivity.
There exists a close association between biochips and tissue regeneration.Biochip technology provides crucial tools and platforms for tissue regeneration, enabling a better understanding of the mechanisms involved by simulating and studying physiological processes within organisms.Additionally, biochips allow precise control and manipulation of cells and tissues through microfluidic and biosensing technologies, promoting their growth and reconstruction.Liu et al. successfully constructed a multi-layered neural network on a biologically patterned and material-regulated biochip by guiding and facilitating the differentiation and network formation of neural stem/progenitor cells (Figure 4E). 100 The biochip consists of a 3 � 3 array of culture wells connected via channels.Immunocytochemistry and impedance measurements were employed to assess the functionality and connectivity of the neural network.The study observed the generation of neurons and the production of functional and recyclable synaptic vesicles.These findings contribute to the development of an artificial brain on a chip, facilitating research on electrical stimulation and recording of multi-layered neural communication and regeneration.
2. 4 | Challenges and future prospects of molecular iPOCT iPOCT requires highly sensitive and reliable sensors and instrumentation.While current molecular detection technologies are already quite advanced, further improvements in sensitivity, selectivity, and speed are needed to meet the demands of complex real-world applications.Moreover, molecular detection generates vast and intricate data sets, presenting a significant challenge in terms of data processing and analysis.This necessitates the development of efficient algorithms and models specifically tailored for iPOCT, capable of swiftly and accurately analyzing large volumes of data and providing reliable analysis results and decision support.Additionally, compared to traditional offline analyses, iPOCT requires real-time acquisition and analysis of sample results.This demands analytical processes with high speed and efficiency, while also ensuring the accuracy and reliability of the obtained results.
Therefore, future developments should focus on advancing sensors with higher sensitivity and precision for real-time monitoring and detection of molecular targets.For instance, the application of nanomaterials, quantum technologies, and optoelectronics holds promise for enhancing sensor performance.By leveraging artificial intelligence methods such as deep learning, reinforcement learning, and machine learning, the efficiency and accuracy of data processing and analysis can be improved, enabling more precise molecular diagnostics.Cloud computing and Internet of Things technologies can facilitate real-time data transmission and remote monitoring, extending the intelligent instant detection to a wider range of application domains.Moreover, strengthening interdisciplinary collaborations among fields such as biology, chemistry, physics, and computer science will drive technological innovation and application exploration, further propelling the development and application of iPOCT.
In conclusion, molecular detection technologies hold significant potential in the field of iPOCT, and with continued advancements and innovation, there is a promising outlook for achieving more efficient and accurate molecular analysis and diagnostics.This can bring about greater convenience and development opportunities in domains such as medicine and biology.

| BIO-SENSING TECHNOLOGY
Biol-sensing technology is a field that utilizes the characteristics and signals of biological systems to perceive and measure biologically relevant parameters.It combines knowledge from biology, chemistry, physics, and engineering, providing us with a novel approach to monitor and understand the activities of living organisms.The biosensing technology itself can be directly combined with smartphones and wearable devices to become a direct iPOCT device on the original basis.It can be broadly categorized into two aspects: biosensors and biological signal processing.Biosensors are devices that convert biochemical or biophysical changes within an organism into measurable signals.These sensors can utilize various biological materials such as enzymes, antibodies, and cells to achieve highly selective and sensitive interactions with specific target molecules.For example, glucose sensors can measure glucose concentrations in blood for diabetes management.Biological signal processing involves the interpretation and analysis of the output signals from biosensors.This includes steps such as signal amplification, filtering, digitization, and data processing.Biological signal processing can extract valuable information about the health status, metabolic activities, and environmental adaptability of organisms, providing useful tools and methods for medical diagnostics, disease monitoring, environmental detection, and drug development.
2][103] These biological sensing technologies play important roles in medical diagnostics, life science research, environmental monitoring, and food safety.Different technologies have different advantages and applicable scopes, allowing for the selection of appropriate techniques based on specific needs for biological monitoring and analysis.Overall, bio-sensing technology is an interdisciplinary field that offers a new paradigm for sensing and understanding the intricacies of biological systems.It holds great potential for advancing our knowledge and applications in various domains.As technology continues to evolve, bio-sensing technology will further enhance its accuracy, speed, and portability, expanding its applications and practicality.

| Surface Plasmon Resonance technology
Surface Plasmon Resonance (SPR) technology, a biosensing technique based on optical principles, offers advantages such as high sensitivity, real-time monitoring, and label-free detection. 104,105It finds applications in studying molecular interactions, binding kinetics of biomolecules, targeted drug development, and disease diagnosis, among other fields.The fundamental principle of SPR technology relies on SPR effects.When a polarized light beam irradiates the interface between a metal film (typically gold or silver) and a medium (usually glass or quartz), electromagnetic waves interact with the free electrons in the metal film, generating surface plasmon waves.When the incident angle (commonly referred to as the resonance angle) is equal to a specific value, the energy of the surface plasmon waves reaches its maximum, resulting in resonant phenomena.Binding of molecules to the surface of the metal film causes changes in the refractive index of the medium, consequently altering the resonance angle. 106Exploiting this principle allows for real-time monitoring and quantitative measurement of the interactions between molecules and the metal film surface.
SPR technology typically employs a total internal reflection optical system for measurements.By introducing a sample solution above the metal film, changes in the incident angle of the light beam are monitored.When molecules bind to the surface of the metal film, it alters the refractive index of the sample solution, thus causing a shift in the resonance angle.By measuring the changes in the resonance angle, quantitative analysis of sample concentration can be performed and affinities of molecules and kinetic parameters (such as association constants, dissociation constants, and rate constants) can be evaluated, enabling the study of biomolecular interactions.SPR technology finds broad applications in life science research, drug screening, and diagnostics.It allows for real-time monitoring of the binding and dissociation processes of biomolecules, enabling the quantitative analysis of interactions among diseaserelated proteins.This contributes to the study of disease mechanisms, identification of diagnostic markers, and drug screening.Additionally, SPR technology can be used for the detection of microorganisms, drug residues, and environmental pollutants.
SPR biosensors can be utilized for real-time and labelfree virus detection.Such biosensors require appropriate sensitivity to meet the demands of clinical diagnostics, such as the diagnosis of COVID-19.In 2022, Dai et al. introduced the concept of advanced laser heterodyne feedback interferometry (LHFI) to further enhance the sensitivity of SPR biosensors (Figure 5A). 39When exciting SPR in the biosensor, LHFI effectively amplifies the intensity changes of light caused by refractive index variations, thus significantly improving the sensitivity.This study immobilized anti-SARS-CoV-2 antibodies on the biosensor surface to achieve specific recognition of viral antigens, demonstrating remarkably low detection limits for the target antigen.These findings highlight the potential utility of LHFI-based SPR biosensors for the rapid diagnosis of COVID-19.The sensitivity issue of SPR sensors can also be overcome by a relatively new optical technique called long-range surface plasmon resonance (LRSPR).Exciting LRSPR in a symmetric dielectric-metal-dielectric structure leads to the formation of a highly sensitive longrange surface plasmon wave, which can accurately detect any changes in the dielectric properties of its surrounding environment.Jain's recent research introduces a LRSPR biosensor based on smartphone-assisted fiber optics, utilizing SiO 2 nanostructured films as the dielectric sensing layer to excite LRSP in a dielectric-metaldielectric structure (Figure 5B). 40The inherent colorsensitive characteristics of the built-in digital camera in smartphones are employed to monitor the intensities of the blue and red channels.This replaces the diffraction gratings or narrowband filters used for spectral data analysis in current reports of smartphone-based SPR sensors, enhancing sensitivity and reducing the chances of erroneous detection.
Localized SPR (LSPR) is a unique form of SPR that arises from the collective electronic charge oscillations in metal nanoparticles excited by a light source, representing an optical phenomenon.Hao et al. employed dendritic poly(amidoamine) macromolecules immobilized on the surface of an LSPR sensor chip as templates for further coupling with specific ligands targeting SARS-F I G U R E 5 (A) Schematic diagram of the biosensor.Reproduced with permission. 39Copyright 2022, Elsevier.(B) Schematic of the prepared smartphone assisted fiber optics -LRSPR uric acid biosensor.Reproduced with permission. 40Copyright 2021, Elsevier.(C) Schematic illustration showing the general approach to prepare LSPR sensor chips.Reproduced with permission. 41Copyright 2023, Elsevier.(D) Schematic representation of the development process of the gold-coated biosensor chip for TB diagnosis.Reproduced with permission. 107Copyright 2022, Elsevier.(E) Schematic diagram of the workflow of the SPR imaging system.Reproduced with permission. 42opyright 2022, Elsevier.

GAO and LI
of 21 CoV-2 (Figure 5C). 41The immobilized dendritic polymers reduced nonspecific adsorption on the surface and increased the density of capture ligands on the sensor chip, thereby enhancing the detection sensitivity.Maphanga et al. developed and analyzed an optical biosensor chip using LSPR to monitor the biomolecular interaction between the Mycobacterium tuberculosis antigen and anti-tuberculosis antibodies (Figure 5D). 107By immobilizing the mycobacterial acid on the gold-coated biosensor chip, it was able to react with the antituberculosis antibodies.Their research findings demonstrate the success of LSPR optical biosensing technology in the detection of anti-tuberculosis antibodies.
Most prism-based SPR experiments involve mounting the chip onto an optical prism using a matching fluid with similar refractive indices.However, the fluidity of the matching fluid can easily affect the transmission of the optical signal.Wang et al. addressed issues of consistency and uniformity in their recent study by utilizing an integrated SPR sensor chip composed of a three-layer structure: a flow layer, a metal layer, and a refractive index-matching layer (Figure 5E). 42This chip can selfadhere onto the optical prism, effectively preventing the formation of bubbles.The integrated SPR sensor chip exhibits high sensitivity in refractive index detection, significantly reducing chip stabilization time.The chip was also used for the detection of κ light chain protein and human serum albumin in urine samples, showing tremendous potential in the field of biomedical iPOCT and other related applications.

| Voltammetric electrochemical technique
Voltammetry, an analytical method based on electrochemical principles, is utilized for studying and measuring the electrochemical behavior and properties of substances.It involves applying controlled potentials to the electrode surface and observing and measuring the resulting current variations.Voltammetry relies on Faraday's law, which describes the relationship between the electrochemical reactions of substances at the electrode surface and the electrode potential.By manipulating the electrode potential, the rate and direction of reactions can be modulated, thereby exploring the electrochemical behavior of substances in solution.Several commonly employed experimental methods in voltammetry include cyclic voltammetry (CV), linear sweep voltammetry, square wave voltammetry (SWV), and differential pulse voltammetry.Among them, CV is the most widely used technique.By changing the scan direction and rate of the electrode potential, CV produces current-potential curves (voltammograms) that provide valuable information.This includes peak potentials, peak currents, and charge transfer processes of the reactions.Such information can be utilized for studying reaction mechanisms, measuring substance concentrations, detecting chemical species, and evaluating electrochemical performances.
Voltammetric electrochemical technique finds widespread applications in various fields.In the realm of analytical chemistry, it can be utilized for pesticide residue detection, environmental pollutant analysis, drug screening, and the fabrication of biosensors.In the field of electrochemical energy, voltammetry plays a crucial role in investigating and evaluating the performance of battery materials, the characteristics of electrolyte interfaces, and electrocatalytic reactions.Additionally, voltammetry is employed in diverse areas such as chemical industry, corrosion research, and materials science.
Screen-printed electrodes (SPCEs) are electrodes prepared using printing technology, known for their highly controllable structure and large electrochemically active surface area.As a user-friendly and versatile electrode material, SPCEs play a crucial role in the field of electrochemical analysis and sensing.Eissa et al. designed a miniaturized electrochemical immunosensor by integrating SPCEs with cotton fibers for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) (Figure 6A). 43The sensor was fabricated on a disposable SPCE coated with carbon nanofibers and measured using SWV.This disposable biosensor can be utilized as a microdevice for sample collection and virus detection, using a portable potentiostat connected to a smartphone.Crapnell et al. combined functionalized SPCEs with thermal detection to monitor the inflammatory biomarker interleukin-6 (IL-6) in human plasma (Figure 6B). 44This system offers a dynamic range that encompasses physiologically relevant concentration levels in both healthy individuals and septic patients, showcasing its significance in the rapid clinical diagnosis of relevant diseases.
Integration is an essential pathway for electrochemical sensors to achieve POCT capabilities.Integration involves combining sensors with signal processing circuits, data acquisition devices, microcontrollers, and other components to enable automation and real-time monitoring.This integration provides greater convenience and flexibility in sensor applications.Additionally, integration allows for miniaturization and portability.By combining electrochemical sensors with microfluidic technology, miniaturized electrodes, and other advancements, sensors can be miniaturized, enabling the development of portable detection devices for applications in medical diagnostics, environmental monitoring, and other fields.Yuksel and his team have designed a precise, rapid, and fully automated electrochemical iPOCT device for quantitative 14 of 21 -GAO and LI detection of human chorionic gonadotropin in human urine samples, used for early pregnancy testing (Figure 6C). 45The device incorporates an automated stirring design, significantly improving surface reaction rates compared to conventional Sandwich assays, enabling rapid detection even at very low concentrations.Zhang et al. developed a portable electrochemical platform integrated with a smartphone for on-skin analysis of Cu 2þ in human sweat, driven by surface tension gradients to facilitate electrolyte flow (Figure 6D). 46This novel sensing system offers a sample collection, rapid detection, lowcost, and user-friendly strategy for the analysis of heavy metal ions in real samples, demonstrating great potential for iPOCT applications.
Wearable electrochemical sensors offer clinically significant information related to personal health and disease states.Gao and his team reported a wearable electrochemical biosensor for continuous analysis of various metabolites and nutrients in sweat, including all essential amino acids and vitamins, during physical exercise and rest. 24This biosensor comprises graphene electrodes capable of in situ regeneration, functionalized with metabolite-specific antibody-mimicking molecularly imprinted polymers and redox-active reporting nanoparticles.It is integrated with sweat induction based on iontophoresis, microfluidic sweat sampling, signal processing, calibration, and a wireless communication module.

| Electrochemiluminescence technology
Electrochemiluminescence (ECL), an analytical technique based on the principles of electrochemistry and luminescence, generates fluorescence signals through electrochemical reactions.It combines the characteristics of both electrochemistry and optics, offering advantages such as high sensitivity, wide linear range, and excellent selectivity.The fundamental principle of ECL involves electrochemical reactions occurring at the electrode surface, resulting in the generation of excited-state species.These excited-state species subsequently undergo radiative decay, emitting photons and producing luminescence signals.In ECL technology, electrochemiluminescent reagents are typically employed as the fluorescent emitters, as they can undergo electrochemical reactions within the electrochemical system to produce luminescence.ECL possesses numerous advantages.For instance, it eliminates the need for external excitation light sources since the fluorescence signals are spontaneously generated through electrochemical reactions.This simplifies and stabilizes the detection system.Moreover, due to the specificity of fluorescent emitters, the ECL technology offers high selectivity, enabling highly sensitive detection of target molecules.Additionally, ECL technology is characterized by rapid response time, wide linear range, and low detection limits, making it widely applied in areas such as bioanalysis, biosensing, and clinical diagnostics.In the field of bioanalysis and biosensing, ECL technology can be used for the detection and analysis of biomarkers such as proteins, nucleic acids, and cells.Compared to other fluorescence techniques, ECL technology exhibits lower background signal interference, allowing for higher signal-to-background ratios, thus enhancing the accuracy and reliability of detection.In the realm of clinical diagnostics, ECL technology finds extensive application in the detection of tumor markers, infectious disease pathogens, and drug concentrations, among others.
ECL is a highly successful technology for immune detection in clinical diagnostics.Immunoassays based on ECL hold the potential for high-throughput detection of multiple biomarkers simultaneously, making them a current research focus.Guo et al. combined polymer beads loaded with luminescent species with a uniform Sandwich immunoassay, resulting in a multiplex immunoassay without spatially patterned antibodies on a plate or substrate (Figure 7A). 47By utilizing dualresolved ECL signals based on potential and spectra as the readout, they were able to detect three antigens, namely carcinoembryonic antigen, alpha-fetoprotein, and beta-human chorionic gonadotropin, using minimal sample consumption.ECL technology holds potential for practical applications in iPOCT for various human diseases.Lakshmanakumar et al. employed functionalized SPCE in combination with ECL technology to detect ultra-low levels of one cardiac biomarker, C-reactive protein (Figure 7B). 48The developed biosensor possesses all the desirable features for iPOCT, including rapidity, low cost, disposable electrodes, miniaturization, and lower detection limits.Zhou et al. combined colorimetric assay and electrochemiluminescent biosensor for rapid, accurate, and sensitive measurement of a biomarker, microRNA-141 (Figure 7C). 49This sensor offers simplicity, rapidity (with the entire detection process taking about 4 h), high sensitivity, good selectivity, and a wide linear range.The method shows great utility and holds promise for low-cost, highly sensitive micro-RNA iPOCT.ECL also provides several unique advantages for microscopy imaging.Wang et al. proposed a novel ECL nanomitter for real-time multicolor imaging of biomolecules on cell membranes (Figure 7D). 50The nanomitter consists of quantum dots (QDs) with surfaceimmobilized glucose oxidase, which catalyzes the oxidation of glucose to generate the co-reactant hydrogen peroxide (H 2 O 2 ).Due to the continuous availability of the co-reactant, this nanomitter enables continuous realtime imaging with a relatively high signal-to-noise ratio.Thus, by utilizing functionalized multicolor QDs for ECL-based single-particle tracking, it is possible to visualize the dynamic behaviors of individual biomolecules, including molecular interactions, on cell membranes in real time.This novel nanomitter holds promise for advancing research on the dynamics of biomolecules on cell membranes.

F I G U R E 7 (A)
The mechanism of the ECL-based multiplex immunoassay.Reproduced with permission. 47Copyright 2018, American Chemical Society.(B) Schematic diagram of the label-free electrochemical cardiac immunosensor.Reproduced with permission. 48opyright 2021, American Chemical Society.(C) Principle of homogeneous electrochemiluminescence/colorimetric biosensor.Reproduced with permission. 49Copyright 2023, Elsevier.(D) Schematic of ECL nanoemitters for real-time multicolor imaging of biomolecules on cell membranes.Reproduced with permission. 50Copyright 2023, Elsevier.The intelligent real-time detection of biosensing technology holds immense prospects for future development, yet it also faces several challenges.Continuous improvements are required in biosensing technology to achieve higher sensitivity and better selectivity.Novel sensor materials and techniques, such as nanomaterials, biorecognition elements, and surface modifications, will drive the enhancement of sensor performance.Biosensing technology will be integrated with technologies such as the Internet of Things, big data, and cloud computing, enabling real-time monitoring, remote transmission, and intelligent analysis of data.This will elevate the operability, practicality, and level of intelligence in biosensing technology.However, challenges remain due to the presence of complex matrices, interferences, and high background signals in biological samples, which limit the sensitivity and reliability of sensors.Therefore, effective sample pretreatment and selective identification methods are issues that need to be addressed in the future.The vast amount of data generated in biosensing technology requires intelligent processing and analysis.Moreover, privacy protection and data security are urgent matters that need to be addressed to ensure both personal privacy and effective data utilization.
In conclusion, the intelligent real-time detection of biosensing technology will continue to encounter new challenges in the future.However, there are also many directions for development to explore, aiming to improve the performance, functionality, and practicality of sensors and further expand the application scope of biosensing technology.

DIAGNOSIS
iPOCT is a revolutionary technology that enables the realtime detection and monitoring of various disease markers.These devices utilize advanced sensors, machine learning algorithms, and cloud computing technology to provide accurate, fast, and efficient solutions.In the medical field, the application of smart real-time detection devices has shown tremendous potential.By connecting with wearable devices or smartphones, iPOCT can access patients' physiological parameters, health data, and medical information.For example, smart wristbands or watches can continuously monitor indicators such as heart rate, blood pressure, and body temperature in real-time, transmitting the data to iPOCT devices for analysis and diagnosis.The multifunctionality and portability of smartphones also make them ideal tools for iPOCT, enabling the capture, storage, and transmission of diagnostic-related images and test results.Through integration with wearable devices and smartphones, iPOCT achieves a more convenient, rapid, and effective diagnosis and monitoring.These connected devices make the collection, transmission, and processing of medical data more conveniently, while providing doctors and patients with real-time feedback and personalized medical services.With the assistance of artificial intelligence in analysis, iPOCT can improve the accuracy and efficiency of diagnosis and play a crucial role in early disease prevention and intervention.This section will provide a detailed overview of real-world application examples of disease diagnosis using iPOCT methods.These examples will offer valuable references and insights into the development and clinical implementation of iPOCT technology.
In the field of immune diagnostics, iPOCT devices can be used for rapid detection of infectious diseases, autoimmune diseases, tumor markers, and other related indicators.For instance, some smart real-time detection devices can determine the presence or absence of antibodies or antigens to determine whether an individual is infected with a certain pathogen.Additionally, some devices can also perform quantitative measurements of specific biomarkers to aid in the diagnosis and monitoring of disease progression.In 2023, Hu et al. developed an automated sample input-output POCT immunodiagnostic platform called DropLab, based on magnetic digital microfluidics technology (Figure 8A). 51DropLab enables microbead-based ELISA for more sensitive and quantitative detection results, achieving full automation and convenient operation.The detection samples can be run in parallel on a thermoformed disposable chip, significantly improving throughput and accuracy compared to other POCT immunodiagnostic devices.In 2022, Macchia et al. designed a handheld, ultra-portable, and fully integrated single-molecule BioScreen binary platform (Figure 8B). 52The platform is based on antigen immunodetection and combined with artificial intelligence, allowing it to connect to smart devices via Bluetooth.This modular system has been proven to directly detect antigens of viruses such as SARS-CoV-2 in patient saliva, serum, and swabs.Panpradist et al. developed Harmony COVID-19 for the detection of SARS-CoV-2 (Figure 8C). 53armony achieves iPOCT testing through off-the-shelf assay reagents, an easy-to-use dedicated smartphone interface, and inexpensive isothermal heaters/detectors.Once the device detects the virus, the results are uploaded to the smartphone for timely early-stage treatment of the disease.Harmony is a complete testing system for sample-to-result analysis, demonstrating high accuracy in both general laboratory and patient care settings.
In recent years, wearable biosensors have garnered significant attention in the rapid detection and monitoring of biomarkers such as small-molecule metabolites in bodily fluids.A recent study conducted by Fan et al. in 2022 focused on the development of a sensitive iPOCT platform for the digital quantification of salivary uric acid, using a colorimetric reaction on a smartphone-assisted microfluidic paper-based analytical device (Figure 8D). 54y analyzing the intensity of Prussian blue on the paper, and leveraging MATLAB code or smartphone applications, this platform enables accurate quantification of uric acid levels.The intelligent detection platform provides a sensitive, rapid, cost-effective, and reliable tool for noninvasive quantitative measurement of salivary uric acid, aiding in the early diagnosis of health issues associated with abnormal uric acid levels.Furthermore, Xu et al. recently developed an innovative non-invasive eye-mask wearable biosensor that can simultaneously detect various crucial biomarkers in human tears, such as pH, proteins, ascorbic acid, and glucose (Figure 8E). 55This detection method involves collecting a drop of tears and undergoing a reaction within 30 s, followed by capturing and analyzing the color signals generated in each dye induction zone on the eye-mask using a smartphone.This technology also utilizes the concept of the Internet of Things, enabling data upload to the cloud for recommended model analysis.The iPOCT-integrated system for diabetes treatment offers advanced technology for managing diabetes.Inspired by the characteristics and functions of the animal chewing system, Yang et al. proposed a biomimetic microneedle therapy platform for intelligent and precise diabetes management (Figure 8F). 56The platform is supported by a microcircuit that utilizes a microneedle array for on-demand skin permeation, allowing interstitial fluid to simultaneously detect glucose and physiological ions and deliver insulin subcutaneously.
By employing epidermal sensors functionalized with hybrid carbon nanomaterials, interstitial fluid exudate can sense in an oxygen-rich environment.With its biomimetic, intelligent, non-implantable, and closed-loop characteristics, this system represents a highly advanced system that promotes diabetes treatment and improves human health.

| CONCLUSION
As a significant technological innovation, iPOCT technology is widely applied in various fields due to its characteristics of speed, accuracy, and intelligence.Driven by current technological advancements and societal demands, iPOCT technology is demonstrating a thriving trend and is expected to achieve even greater breakthroughs in the future.Molecular detection technology is one of the core components of iPOCT.Through molecular detection, the chemical composition and concentration of substances can be identified, enabling the analysis of their properties and determination of their presence.Another crucial iPOCT method is biosensing technology.This approach combines the specific recognition properties of biomolecules with sensors for detecting specific biomolecules or biological processes.The key to iPOCT lies in its intelligent data processing and analysis capabilities.Modern iPOCT systems often integrate artificial intelligence and machine learning algorithms, enabling automated processing and analysis of large amounts of data to enhance the accuracy and efficiency of detection.These systems can learn from known data patterns and apply them to the detection of unknown samples, facilitating rapid determination of the test results.
With technological advancements and increasing demand, iPOCT is expected to have a broader scope in the future and become an integral part of the field of smart healthcare.As wearable device technology continues to emerge, iPOCT will also integrate with wearable devices to monitor patients' health indicators in real-time and provide alerts and recommendations in case of abnormalities.The application of iPOCT technology will also drive the development of remote healthcare.Patients will be able to perform necessary tests at home or other locations and transmit the data to healthcare institutions via the Internet, enabling doctors to remotely diagnose and provide treatment recommendations.
In general, the development of iPOCT technology holds significant implications for human health.It promises faster and more accurate diagnosis and treatment solutions, enhancing medical efficiency, facilitating personalized healthcare, and driving the progress of remote healthcare.By combining molecular detection technology and biosensing technology with intelligent data processing and analysis, we can obtain more accurate, reliable, and efficient detection results, providing better life assurance for humanity.The application of iPOCT devices offers new opportunities for early disease diagnosis and treatment, with the potential to improve the efficiency and quality of healthcare and bring about healthier and more convenient lives for individuals.