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Portable and Wearable Sensing Technologies for Biochemical Detection

Xin Li, Fenni Zhang, and Qingjun Liu*

Zhejiang University, Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, No.38, Zheda Road, Hangzhou, 310027, P. R. China

While the first generation of portable or wearable healthcare devices (such as dynamic ECG monitors, oximeters, and sport watches) mainly aims to collect personal physiological information, the advances in biotechnology, miniaturized electronics, and flexible functional materials have fueled the prosperity of portable and wearable biosensor market, which is targeted for disease pre-diagnosis and precise medicine. Owing to their low cost, easy operation, facile readout, and decent detection capability, the arising portable and wearable sensing technologies are highly valued and expected to counter the escalating healthcare demands and challenges. These devices further enable personalized health monitoring and substantially reduce healthcare costs. Coupled with modern data analysis approaches, portable and wearable sensing technologies could open the door for early diagnosis of diseases and precision medicine.

1.1 Biochemical Detection: Increasing Demands and Challenges

Biochemical detections, which measure the biochemical substance (protein, sugar, oxygen, etc.) in body fluid, have been widely used in clinical settings for both disease diagnosis and management. In the past decades, biochemical detections were mainly performed at the laboratory site with bulky and expensive instruments and by specialized professionals for critical disease diagnosis and microbial identification [1]. Nowadays, with the increasing prevalence of the growing population, aging, and chronic diseases continuously rising healthcare costs, the healthcare system is undergoing a vital transformation from a traditional hospital-centered system to an individual-centered system [2, 3]. Therefore, there is an urgent demand for a more efficient method for on-site biochemical detection for applications of critical disease diagnosis and control and for continuous in situ biochemical detection for personal health monitoring and chronic disease management.

For critical disease diagnosis and control, rapid and accurate biochemical detection for personal precision medicine is still challenging. Many biochemical molecules are present at very low concentrations in complex samples. Infectious diseases are one major type of critical disease, serving as the second leading cause of mortality around the world [4, 5]. The recent outbreaks of life-threatening pandemic diseases (such as the Covid-19 pandemic) have also greatly impacted global healthcare as well as society and economic development [6, 7]. Each infectious disease is caused by specific pathogenic microorganisms, including viruses, bacteria, fungi, and parasites, and rapid and accurate identification of these pathogens is key for controlling the outbreak of threatening infectious diseases. However, the current biochemical detection process of pathogenic microorganisms is complex and requires time-consuming sample processing and multiple detection steps with laboratory equipment, which makes it difficult to meet the actual needs [8]. It is critical to develop rapid on-site detection technology with the availability of easy-to-use, low-cost, and robust diagnostic tests for efficient biochemical detection. The WHO has developed a set of generic guidelines for the development of diagnostic tests appropriate for the developing world that can be summarized under the acronym ASSURED: affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and delivered to those who need it [9].

Except for the rapid and accurate diagnosis and prognosis of acute diseases, in situ biochemical detection is another challenge for the continuous monitoring and management of chronic diseases to achieve personal healthcare and precision medicine. Chronic diseases, such as diabetes and cardiovascular disease, are major health concerns requiring ongoing monitoring and management to prevent them [10]. The human body is a complex biological system, exhibiting a myriad of changing physiological signals that reflect the ongoing physiological processes within the body [11]. The detection and quantification of such real-time biochemical and biophysical signals with body-integrated sensors provide key opportunities for the advancement of personal healthcare. Therefore, there is an increasing demand for developing body-integrated portable and wearable techniques for continuous biochemical monitoring.

1.2 Portable Sensing Technologies: Efficient Biochemical Analysis

As mentioned earlier, biochemical detections play an irreplaceable role in human society. However, conventional biochemical detections are usually limited to the quantitative analysis of various biomarkers and biochemical parameters in biological samples in laboratories under demanding conditions, and the detection process is complex and time consuming [12]. As the economy develops, efficient and portable biochemical detections are in urgent demand for an increasing number of applications [13]. Easily integrated sensing technologies have been designed and developed to meet these needs. In recent years, diverse combinations of technologies have emerged to address the strengths and weaknesses of different detection techniques, greatly improving the detection of biochemical substances, and sensors have been extensively and intensively researched in recent years. As with conventional microbiological detection techniques, the relatively well-developed biochemical techniques combined with biosensors are mostly used for the initial processing of samples. Immunosensors constructed by introducing fast detection speed into biosensors have been widely used for the detection of biochemical substances. Molecular technology, as a new technology, can improve the sensor and is mostly used for the recognition element and signal amplification of the sensor.

With the rapid advances in modern science and technology, this emerging cross-disciplinary field combines the advantages of multiple fields of technology to become an effective biochemical analysis modality with great promise for the rapid and accurate detection and quantification of biochemical substances [14].

As an important analytical technique for biochemical detection, sensing technology is a technique that uses identification elements as biosensing units to convert difficult-to-detect biological signals into detectable signals using appropriate transduction principles. Sensing technology can be used to detect a wide range of analytes in samples of different matrices [15]. The sensors are widely used for their short detection time, fast analysis, and easy integration and have become a popular research area [8].

The increasing demand for rapid and accurate detection of biochemicals is providing opportunities for the development of portable sensing tests [16]. There is a trend to develop miniaturized sensing devices that fully integrate all steps of biochemical testing [3, 17]. Microfluidic systems have been created to improve experimental efficiency and device portability. Compared to other analytical techniques, microfluidics flexibly combines multiple operating units such as sample preparation, reagent manipulation, biological reactions, and detection steps, showing advantages such as system integration, device miniaturization, portability, automation of operating processes, low reagent consumption, elimination of human interference, prevention of contamination, easy integration with other technical equipment, and good compatibility [18, 19]. The aforementioned properties of microfluidic technology have made experiments on a chip a reality from a conceptual point of view. This shift from the traditional central laboratory to experiments on a chip has revolutionized many researchers. Work that previously needed to be done in the laboratory can now be done on a chip. All chambers and valves can be integrated together to perform complex operations with precision. To prevent cross-contamination, different channels for various analyses can be made into closed chambers [20]. Simplify complex analytical protocols and reduce sample volumes, assay times, and reagent costs. Microfluidic technology improves the efficiency and portability of biosensors for outdoor operation, allowing for the simultaneous detection of multiple samples or multiple target microorganisms [21], increasing their utility and flexibility. Li et al. used microfluidic chip fluorescence assays to identify three drug-associated mutational messages from the same sample [22]. The integration of microfluidics with biosensors simultaneously provides the basis for the combination of biosensors and smart devices. They can be made flexible and portable; enable real-time, continuous, and rapid detection; and offer unique advantages such as miniaturization, high sensitivity, and label-free [23]. The introduction of smart devices has greatly improved microbial detection and provided easy data processing and transmission for demonstration purposes. A useful exploration using capillary microfluidic devices in conjunction with smart devices was carried out by Hassan et al. [24]

Among the different biosensing technologies, portable sensing technologies offer...