Organic bioelectronic implants exhibit adaptability by incorporating sensors to monitor vital physiological parameters like pH, temperature, glucose levels, or specific biomarkers. Additionally, they integrate stimulating components such as electrodes or transducers that are capable of delivering targeted electrical or chemical signals. These signals serve therapeutic objectives such as deep brain stimulation or promoting neural regeneration. To ensure the longevity and efficacy of the implant, it is encapsulated within biocompatible materials or coatings. This encapsulation acts as a protective barrier against unwanted interactions with the surrounding biological environment.
4. Fabrication Methods
Organic bioelectronic devices are predominantly fabricated/patterned using several approaches, such as organic thin-film deposition methods, patterning techniques, 3D printing, and organic synthesis.
Organic thin-film deposition: These methods are widely used for depositing thin films of organic materials on substrates with controlled thickness and uniformity. One common technique is spin coating. In spin coating, an organic material solution, such as semiconductors, conductive polymers, or other active components, is deposited onto a flat substrate, typically a silicon wafer or glass, which can be further integrated into a device (see schematics in Figure 5).
Figure 5. Schematic diagram of various fabrication methods: (a) spin-coating process; (b) photolithography; (c) dip-pen nanolithography (DPN); (d) microcontact printing (μCP); (e) direct ink writing (DIW).
Vacuum evaporation is another thin-film deposition method. It facilitates the precise deposition of organic materials onto various substrates under reduced pressure conditions. In this process, organic materials, such as semiconductors, conductive polymers, and other key bioelectronic components, are heated to their vaporization points and then allowed to condense onto the target substrate, thereby creating thin organic films with exceptional uniformity and precise thickness control. This level of control is indispensable in developing organic electronic devices, including organic field-effect transistors (OFETs) and organic photodetectors, where the properties of the organic layer directly influence the device performance. Vacuum evaporation enables the sequential deposition of multiple organic layers, thereby making it possible to design complex device architectures. This capability is invaluable, as organic bioelectronic devices often require distinct functional layers for sensing, signal processing, and data transmission.
Photolithography: It is a well-established technique for patterning organic materials at micron and submicron scales. The photolithography process begins with a substrate, typically made of silicon or glass, that is coated with a layer of photoresist, which is a photosensitive organic material. A photomask containing the desired pattern is placed near the photoresist-coated substrate, and the entire assembly is exposed to ultraviolet (UV) light. The exposed regions undergo a chemical change, thereby making them either more soluble (in the case of positive photoresists) or less soluble (for negative photoresists) in a developer solution, which depends on the type of photoresist used.
Electron-Beam (e-beam) Lithography: Electron-beam lithography or EBL is an advanced nanofabrication technique that operates on the fundamental principle of using a focused beam of electrons to create incredibly fine patterns and structures at the nanometer scale. It has found applications in various fields, including semiconductor device fabrication, nanotechnology, and microelectromechanical systems (MEMS).
Dip-Pen Nanolithography (DPN): DPN is an advanced nanofabrication technique that leverages the precision of scanning probe microscopy (SPM) for the controlled deposition of molecules, nanoparticles, or biomolecules onto a substrate with nanometer-scale precision. In this method, an atomic force microscope (AFM) tip coated with an “ink” material is submerged, or “dipped”, into the ink and then brought into contact with a substrate under the guidance of the AFM.
Microcontact Printing (μCP): μCP is a widely used soft lithography technique employed for precise and controlled deposition of materials, often in the form of self-assembled monolayers (SAMs), on a substrate. The process is akin to conventional rubber stamp printing but on a micro- and nanoscale. μCP employs an elastomeric stamp, usually made of polydimethylsiloxane (PDMS), that is engineered with relief microstructures or patterns on its surface. The stamp is coated with an “ink” or material, which adheres only to the relief patterns. The stamp is then gently brought into contact with a substrate, thereby transferring the material onto the substrate in the desired pattern.
Inkjet Printing: Inkjet printing, a highly versatile technique, has become integral to the realm of organic bioelectronics. The process involves depositing minuscule ink droplets onto a substrate, thus enabling controlled patterning of various functional materials, including organic semiconductors, conductive polymers, and biologically relevant molecules. Its prominence in this field stems from multiple advantages, such as exceptional precision and resolution, broad material compatibility, reduced material wastage due to its additive nature, high levels of customization to adapt complex designs for specific applications, noncontact printing, and scalability that accommodates everything from research-level prototyping to large-scale production
[97][98][99][100].
Laser Writing: Laser writing, also known as laser-induced forward transfer (LIFT), is an advanced microfabrication technique that employs a high-intensity laser beam to transfer material from a donor layer to a receiver substrate, thereby enabling the precise deposition of micro- or nanoscale features. A laser pulse generates a shockwave within the donor material, thus propelling a small amount of material toward a transparent receiver substrate placed above it. This method offers exceptional precision, thereby allowing for fine control over the position and size of the deposited material and making it ideal for creating intricate patterns, microarrays, and electronic devices. One of its significant advantages is versatility, as it can be used with various materials, including organic polymers, conductive substances, and biological compounds, thereby making it suitable for applications ranging from organic electronics to biosensors.
3D Printing: The field of bioelectronics has witnessed remarkable progress with the integration of 3D printing technologies. These technologies are known for their streamlined processes, which empower the creation of intricate three-dimensional structures with exceptional precision, scalability, and adaptability
[101][102][103]. Various 3D printing techniques, including fuse deposition modeling (FDM), stereolithography (SLA), digital light processing (DLP), selective laser sintering (SLS), and direct ink writing (DIW), have been instrumental in patterning and fabricating materials with diverse strategies.
Chemical Methods: Organic bioelectronic devices can also be fabricated through diverse chemical methods, including polymerization, chemical vapor deposition (CVD), and self-assembly
[104][105][106][107][108][109][110]. These methods allow for precise control over the molecular structure of the materials, thereby enabling the design of custom organic semiconductors, conductive polymers, and biocompatible coatings.
5. Biosensing Mechanisms
A typical biosensor comprises several fundamental components: the target analytes, receptors or biorecognition elements, a transducer, and output systems
[111][112]. The target analyte is the specific substance under investigation, such as glucose, ammonia, alcohol, or lactose. Bioreceptors are biomolecules or biological entities that are capable of recognizing and binding to the target analyte. Examples of biorecognition components include enzymes, cells, aptamers, DNA/RNA strands, and antibodies. The role of the transducer is to convert the biorecognition event into a measurable signal, typically in the form of an electrical signal, which correlates with the quantity or presence of the chemical or biological target. This conversion process is known as signalization. Transducers generate optical or electrical signals that directly correspond to the interactions between the analytes and bioreceptors. Finally, output systems encompass signal processing, amplification, and display units, thereby facilitating the interpretation and presentation of the biosensor’s results.
Figure 6 illustrates the components of the typical biosensor.
Figure 6. Schematic illustration of key components of a typical biosensor.
5.1. Electrochemical Sensing
Electrochemical sensing is a powerful mechanism that is utilized in organic bioelectronics for detecting and quantifying various biomolecules and chemical species. This sensing platform measures electrical signals generated during electrochemical reactions at the interface between the organic material and the target analyte. Organic electrochemical sensors offer high sensitivity, rapid response times, and excellent selectivity, thereby making them valuable medical diagnostics, environmental monitoring, and point-of-care testing tools. The fundamental principle behind electrochemical sensing in organic bioelectronics lies in the redox properties of organic materials, which can undergo reversible electron transfer reactions
[113][114]. These redox-active organic materials, such as conducting polymers, redox enzymes, or organic nanoparticles, are integrated into the sensing platform to act as the transducer element. Electrochemical sensing involves two main components: an electrode and a redox reaction with the target analyte. The sensing platform typically comprises working (or indicator electrode), reference, and counter electrodes (in some cases, the two-electrode system can be used for electrochemical sensing)
[115][116]. The working electrode (WE) is coated with the redox-active organic material, where the electrochemical reaction with the target analyte occurs. The reference electrode (RE) maintains a constant potential against which the working electrode’s potential is measured. The counter electrode (CE) completes the electrical circuit and balances the current flow during the electrochemical reaction.
Amperometric Sensing: Amperometric biosensors are a type of electrochemical biosensor used for quantitatively detecting and analyzing biological analytes. These biosensors rely on the measurement of the current generated from an electrochemical redox reaction at the sensor’s working electrode surface when the target analyte interacts with a biorecognition element (such as enzymes, antibodies, or nucleic acids) that is immobilized on the electrode. The basic setup of an amperometric biosensor typically consists of three main components: the working electrode, the reference electrode, and the counter electrode. The biorecognition element is immobilized in the working electrode, and the redox reaction occurs upon the binding of the target analyte. The reference electrode maintains a constant potential, while the counter electrode completes the electrical circuit, thus allowing the flow of electrons during the redox reaction.
Voltammetric Biosensing: Voltammetric biosensors are a type of electrochemical biosensor that rely on the measurement of the current as a function of an applied voltage or potential at the sensor’s working electrode. These biosensors use the principles of voltammetry to detect and quantify the target analyte in a sample. The basic setup of a voltammetric biosensor includes a working electrode coated with a biorecognition element, a reference electrode, and a counter electrode. When an increasing or decreasing voltage is applied to the working electrode, a redox reaction occurs at the electrode surface, involving the oxidation and reduction of electroactive species.
Potentiometric Sensing: Potentiometric biosensors are a type of electrochemical biosensor used for the quantitative detection and analysis of biological analytes. Unlike amperometric biosensors that measure the current generated from a redox reaction, potentiometric biosensors rely on measuring potential or voltage changes at the sensor’s working electrode surface when the target analyte interacts with a biorecognition element. The basic setup of a potentiometric biosensor includes a working electrode and a reference electrode
[117]. The working electrode is coated with biorecognition elements, such as enzymes, antibodies, or nucleic acids, which interact with the target analyte in the sample.
Impedimetric Sensing: Impedimetric biosensors are a type of electrochemical biosensor that measure the electrical impedance or resistance changes at the sensor’s working electrode surface in response to the interaction between a biorecognition element and the target analyte.
Impedance-based biosensors can be classified into two main types: capacitive and conductive. Capacitive impedance biosensors rely on changes in the dielectric properties of the interface between the sensing element and the target analyte. When the analyte binds to the immobilized biomolecules, it alters the dielectric constant and thickness of the insulating layer, thereby leading to changes in the electrode’s capacitance. These changes are then measured and related to the concentration of the analyte.
5.2. Optical Sensing
Optical sensing utilizes the interaction between light and organic materials to detect and quantify biological or chemical analytes. These sensing platforms employ organic materials, such as organic semiconductors, fluorescent dyes, or organic nanoparticles, which are integrated into photonic or optoelectronic devices to facilitate the sensitive and selective detection of target molecules. The fundamental principle behind optical sensing in organic bioelectronics relies on the optical properties of the organic materials, which can absorb, emit, or scatter light in response to changes in their environment. Within the realm of optical biosensors, various types have been developed, with each catering to specific applications and detection requirements
[118][119].
Surface plasmon resonance (SPR) biosensors, one of the most well-known optical biosensors, rely on the principle of plasmon resonance, which occurs when light interacts with the collective oscillations of electrons on a metal surface
[120]. Changes in the refractive index due to binding events on the sensor surface lead to alterations in the resonance angle, thereby enabling the label-free and real-time detection of molecular interactions.
Surface-enhanced Raman scattering (SERS) biosensors leverage the enhancement of Raman scattering signals when molecules are adsorbed on roughened metal surfaces. Molecules adsorbed on these surfaces generate unique Raman spectra, thereby enabling molecular identification and quantification. SERS stands out as an exceptionally sensitive method for identifying low-concentration molecules. It excels in detecting various substances, such as DNA, microRNA, proteins, blood components, and bacteria. Furthermore, it facilitates the detection and characterization of individual cells, aids in bioimaging, and plays a pivotal role in diagnosing various diseases. Its unique ability to offer extensive structural insights into biological analytes adds significant value to the field of analytical science and diagnostics
[121].
Fluorescence is a widely used optical phenomenon for biosensing
[122]. In fluorescence-based optical sensing, organic fluorescent dyes or fluorophores are used as the sensing elements. When excited with a specific wavelength of light, these fluorescent molecules absorb energy and become excited to higher energy states. Subsequently, they release this excess energy through fluorescence emission at a longer wavelength. The intensity of the emitted fluorescence signal is directly proportional to the concentration of the target analyte, thereby enabling quantitative detection.
Photonic crystal optical biosensors harness the unique properties of photonic crystals to enable the sensitive and specific detection of biomolecular interactions
[123]. These biosensors operate on the principle of modifying the transmission or reflection of light when target molecules bind to the sensor surface. Photonic crystals are engineered materials with periodic structures that create band gaps in the electromagnetic spectrum.
Interferometric biosensors utilize the interference patterns generated when light waves interact. By measuring changes in the phase or intensity, these sensors detect biomolecular interactions. Fabry–Perot interferometers and Mach–Zehnder interferometers are commonly used in this category. A Fabry–Perot interferometer exploits multiple-beam interference within a resonant optical cavity to precisely measure the wavelengths of light. It consists of two parallel mirrors with a small separation distance, thus creating a resonant cavity. When light is introduced into the cavity, it reflects repeatedly between these mirrors, thereby leading to constructive and destructive interference between the multiple reflected beams. Constructive interference enhances the intensity of light at specific wavelengths, while destructive interference reduces it at others, thus producing a pattern of interference fringes. By analyzing these fringes and their variations, Fabry–Perot interferometers can be used to determine the wavelengths of light and facilitate high-resolution spectral analysis. Mach–Zehnder interferometers are typically used in integrated optical biosensors.
Optical fiber biosensors employ optical fibers as a core component for detecting and quantifying biological or chemical substances. These sensors are characterized by their capacity to harness light transmission through optical fibers for sensitive and real-time detection. The basic operation typically involves recognition elements, such as antibodies, enzymes, or other bioactive molecules, which are immobilized on the fiber’s surface. When the target analyte binds to this recognition element, it changes the fiber’s optical properties, such as light intensity, wavelength, or polarization. These changes are then quantified and correlated to the concentration of the target analyte. These sensors are compact, versatile, immune to electromagnetic interference, and suitable for remote sensing.
5.3. Piezoelectric Sensing
Piezoelectric biosensing is a powerful and versatile real-time mechanism that is used to detect and quantify biomolecular interactions. This sensing mechanism leverages the piezoelectric effect of certain materials, such as quartz or piezoelectric polymers, to transduce biomolecular binding events into measurable electrical signals. These mass-based biosensors are widely used in biomedical research, diagnostics, and pharmaceutical development due to their label-free, sensitive, and rapid detection capabilities.
The fundamental principle behind piezoelectric biosensing lies in the piezoelectric materials’ ability to convert mechanical stress into electrical signals. The biosensing platform typically consists of a piezoelectric transducer, such as a quartz crystal microbalance (QCM) or a piezoelectric polymer-coated cantilever, which is functionalized with specific biorecognition elements
[124][125]. These biorecognition elements, such as antibodies, DNA, or enzymes, are carefully immobilized on the surface of the piezoelectric material. When the biosensing platform comes into contact with a biological sample, such as a solution containing biomolecules of interest (e.g., proteins, DNA, or antigens), the biorecognition elements interact selectively with the target biomolecules. This interaction leads to the formation of biomolecular complexes, thereby causing an increase in the mass or stiffness of the layer attached to the piezoelectric material.
6. Biosensing Applications
6.1. Medical Diagnostics
Organic bioelectronics have emerged as a promising technology in medical diagnostics, thus offering unique advantages for noninvasive and point-of-care testing. By leveraging organic materials’ electrical and biological properties, organic bioelectronics facilitates the development of sensitive, portable, and cost-effective diagnostic devices
[126][127][128].
Organic bioelectronic biosensors have opened up new possibilities in disease biomarker detection, thereby enabling the identification of specific biomolecules in biological fluids like blood, saliva, and urine
[129][130]. These biosensors can be customized to detect disease-related biomarkers associated with conditions such as cancer, cardiovascular disorders, and infectious diseases, thereby facilitating early diagnosis and timely intervention. In the realm of diagnostics, organic bioelectronics play a central role in the miniaturization of diagnostic platforms, thus giving rise to lab-on-a-chip (LOC) devices
[131][132]. LOC diagnostics offer rapid and multiplexed testing with minimal sample volume requirements, thus making them ideal for point-of-care settings and reducing the strain on centralized healthcare facilities. The use of organic bioelectronics extends to electrochemical and electronic immunoassays, thus providing highly sensitive and specific detection of antigens and antibodies. These assays allow for the precise quantification of disease-related molecules, thus supporting accurate diagnosis and monitoring of disease progression. Nucleic acid analysis is another application of organic bioelectronics, thereby enabling the detection of DNA and RNA sequences associated with genetic disorders and infectious agents
[133][134]. This technology is essential for genetic screening, personalized medicine, and pathogen identification. In medical imaging, organic bioelectronics have shown promise in developing imaging probes and contrast agents, thereby enhancing the resolution and sensitivity of imaging techniques like magnetic resonance imaging (MRI)
[135][136].
6.2. Wearable Health Monitors
Organic bioelectronics have gained considerable traction as a technology for wearable health monitoring systems, thereby offering exceptional versatility and performance. Wearable devices can seamlessly integrate into daily life by leveraging organic materials’ unique properties, including flexibility, biocompatibility, and tunable electronics
[137][138]. Applying organic bioelectronic sensors allows for the continuous and noninvasive monitoring of vital signs, such as heart rate
[139], blood pressure
[140], respiration rate
[141][142], body temperature
[143], pulse
[144], glucose levels in individuals with diabetes
[145], pH levels
[146], and the human stress hormone cortisol
[147]. Also, organic wearable bioelectronics have been widely used for chronic wound biosensing and on-demand therapy administration
[148][149].
Furthermore, organic bioelectronics enable the recording of electrocardiogram (ECG) signals for the early detection of cardiac abnormalities while monitoring skin conditions, muscle activity during physical activities, sleep patterns, stress levels, and emotions, thereby contributing to a comprehensive health assessment
[150][151][152]. These wearable systems can also track environmental factors like air quality and temperature, as well as provide secure biometric authentication for enhanced data security. By combining diverse functionalities, organic bioelectronics empower individuals to control their health proactively, thus enabling real-time remote monitoring, personalized drug delivery, and improved overall health management and outcomes
[153][154]. As research continues, further advancements in organic bioelectronics promise to revolutionize wearable health monitoring technology and its potential impact on healthcare.
6.3. Environmental Monitoring
Organic bioelectronics have demonstrated significant promise across diverse environmental monitoring applications due to their unique attributes, cost-effectiveness, and compatibility with biological systems. These applications achieve more efficient and sustainable monitoring solutions by leveraging organic electronic devices. Key areas of organic bioelectronics applications in environmental monitoring include water quality management and monitoring, thereby enabling the real-time detection of various pollutants in water bodies; air quality monitoring to track air pollution levels continuously; and soil health assessment, which all aid in precision agriculture.
In water quality management, organic bioelectronics are crucial in detecting and quantifying water pollutants such as heavy metals, organic compounds, and microorganisms
[155][156]. Organic bioelectronic sensors offer high sensitivity and selectivity, thereby enabling real-time water quality monitoring in lakes, rivers, and wastewater treatment facilities
[157][158]. These sensors can help identify contamination sources, assess the effectiveness of water treatment processes, and ensure compliance with regulatory standards, thereby preserving water resources and safeguarding aquatic ecosystems.
6.4. Food Safety and Quality Control
Organic bioelectronics has emerged as a promising technology for food safety and quality control applications
[159][160][161][162]. Their unique properties, including biocompatibility and sensitivity to biological molecules, make them well suited for detecting contaminants, spoilage, and quality indicators in food products. Key applications include detecting food contaminants like pesticides and pathogens, monitoring food spoilage, assessing food quality indicators, and detecting allergens. Organic bioelectronics allows for real-time monitoring of food production processes and on-site testing, thus contributing to consistent quality and safety. Additionally, they can be integrated into smart packaging to monitor food quality during storage and transportation. This technology aids in verifying food authenticity, detecting adulteration, and ensuring agricultural production safety by monitoring pesticide residues on crops. Embracing organic bioelectronics in food safety and quality control enhances consumer protection, reduces food waste, and strengthens food safety regulations.
7. Conclusions
Organic electronics in biosensing represent a promising and dynamic frontier with far-reaching implications for medical and environmental applications. This exciting convergence of organic materials and bioelectronics has unlocked new opportunities for the precise, sensitive, and real-time detection of biomolecules and chemical species, thereby transforming the landscape of medical diagnostics and environmental monitoring.
The unique properties of organic materials, such as biocompatibility, flexibility, and tunability, have paved the way for developing innovative biosensing devices with diverse applications. From implantable biosensors for continuous health monitoring to wearable devices enabling personalized diagnostics, organic bioelectronics offer groundbreaking solutions that bridge the gap between traditional sensing technologies and cutting-edge medical practices. In medical diagnostics, organic bioelectronic sensors offer the potential to revolutionize disease detection and management. These sensors’ label-free and real-time monitoring capabilities enable the rapid and accurate analysis of biomarkers, thereby facilitating early disease diagnosis and tailored treatment plans. Moreover, integrating organic bioelectronics into wearable health monitoring systems empowers individuals to actively participate in their healthcare, thereby promoting proactive and personalized health management. Beyond medical applications, the versatility of organic bioelectronics finds significant relevance in environmental monitoring. From detecting pollutants and toxins to monitoring changes in environmental parameters, organic bioelectronic sensors contribute to sustainable environmental management and conservation efforts. These sensors offer the potential for the rapid and efficient detection of environmental threats, thereby enabling timely interventions and preserving ecological balance. However, as with any emerging technology, organic electronics in biosensing face challenges that warrant attention. Issues related to biocompatibility, stability, scalability, and manufacturing consistency must be addressed to ensure these biosensing platforms’ reliability and long-term performance.