Sensors are key tools for monitoring the dynamic changes of biomolecules and biofunctions that encode valuable information that helps us understand underlying biological processes of fundamental importance. Because of their distinctive size-dependent physicochemical properties, materials with nanometer scales have recently emerged as promising candidates for biological sensing applications by offering unique insights into real-time changes of key physiological parameters.
Nano sensors are chemical or mechanical sensors that can be used to detect the presence of chemical species and nanoparticles, or monitor physical parameters such as temperature, on the nanoscale. They are nanoscale devices that measure physical quantities and convert these to signals that can be detected and analyzed. There are several ways proposed today to make nano-sensors; these include top-down lithography, bottom-up assembly, and molecular self-assembly. Nanomaterials-based sensors have several benefits in sensitivity and specificity over sensors made from traditional materials, due to nanomaterial features which is not present in bulk material that arise at the nanoscale. Nano sensors can have increased specificity because they operate at a similar scale as natural biological processes, allowing functionalization with chemical and biological molecules, with recognition events that cause detectable physical changes. Enhancements in sensitivity stem from the high surface-to-volume ratio of nanomaterials, as well as novel physical properties of nanomaterials that can be used as the basis for detection, including nano-photonics. Potential applications for nano sensors include medicine, detection of contaminants and pathogens, and monitoring manufacturing processes and transportation systems. By measuring changes in physical properties (volume, concentration, displacement and velocity, gravitational, electrical and magnetic forces, pressure or temperature) nano-sensors may be able to distinguish between and recognize certain cells at the molecular level in order to deliver medicine or monitor development to specific places in the body. The type of signal transduction defines the major classification system for nano-sensors. Some of the main types of nano-sensor readouts include optical, mechanical, vibrational, or electromagnetic. There are different types of nano-sensors in the market and in development for various applications, most notably in defense, environmental, and healthcare industries. These sensors share the same basic workflow: a selective binding of an analyte, signal generation from the interaction of the nano-sensor with the bio-element, and processing of the signal into useful metrics. Thus, nano-sensors can be designed for understanding vital metrics of people. In this way, several research and experiments are being conducted on different subjects.
Wearable sensors for monitoring the physiological and biochemical profile of the athlete
Athletes are continually seeking new technologies and therapies to gain a competitive edge to maximize their health and performance. Athletes have gravitated toward the use of wearable sensors to monitor their training and recovery. Wearable technologies currently utilized by sports teams monitor both the internal and external workload of athletes. However, there remains an unmet medical need by the sports community to gain further insight into the internal workload of the athlete to tailor recovery protocols to each athlete. The ability to monitor biomarkers from saliva or sweat in a noninvasive and continuous manner remain the next technological gap for sports medical personnel to tailor hydration and recovery protocols per the athlete.
Biomedical sensors present an exciting opportunity to measure human physiologic parameters in a continuous, real-time, and nonintrusive manner by leveraging semiconductor and flexible electronics packaging technology. These sensors incorporate a broad range of advances in microelectromechanical (MEMS), biological and chemical sensing, electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG)-based neural sensing platforms. Biological and chemical sensors are increasingly viewed as promising alternatives to expensive analytical instruments in the health care industry when specificity and selectivity criteria are met. The development of electrochemical transducers has been especially promising due to their low cost, simplicity, and portability. The emergence of wearable biosensors to measure analytes from eccrine sweat to assess the performance and mental acuity of the athlete serve as next steps to assessing human performance.
High-sensitivity nano-sensors for biomarker detection
High sensitivity nano-sensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples.
One of the key challenges in disease control and prevention is early detection. Better clinical outcomes are directly linked with early detection of disease, enabling effective treatment to reduce the suffering and cost to society associated with the disease. However, traditional screening methods such as biopsy, blood detection and clinical imaging are currently not very powerful at very early stages, quite costly and not available to many patients. The use of disease biomarkers is emerging as one of the most promising strategies for our understanding of disease biology and disease management. A biomarker is an indicator of a biological state or condition. It can be a protein, a fragment of a protein, DNA/RNA, or an organic chemical made by abnormal cells. A disease biomarker is a ‘molecular signature’ of the physiological state of a disease at a specific time and is therefore extremely important for early detection and accurate staging of disease. Disease biomarkers also provide information on the underlying mechanism of the initiation of a disease and ultimately offer powerful methods to diagnose and treat the disease at a desired time. Traditional diagnostic methods, especially for cancer, are based on endoscopy, computed tomography, X-rays, positron emission tomography, mammography and magnetic resonance imaging. However, these methods are neither accessible to large populations nor practical for repeated screenings at early stages of disease. Nanotechnology may be the answer to this need and is already playing an increasingly important role in the improvement of biosensing. Nano-sensors are devices that sense a force, chemical or biological, where a portion of the sensor operates at the nanoscale. Generally, nano-sensors are based on nanoparticles that are conjugated to a targeting ligand where the ligand finds the specific marker of interest, giving the nano-sensor specificity, and the nanoparticle acts as the generator or detector of a signal, assigning sensitivity. Nanoparticles offer desirable and unmatched characteristics for detection such as high reactivity, increased electrical conductivity, strength, unique magnetic properties and significant surface area to volume ratio. For example, nanoparticles due to their high surface area to volume ratio can detect a high concentration of markers at extremely limiting amounts of the sample. Additionally, nano-sensors offer the use of multi-parametric analysis for real time and direct read outs of detection signals. Furthermore, nanoscale properties are tunable by their shape; therefore, nanotubes, nanowires, thin films, and nanocantilevers give nano-sensors versatile and high-sensitivity detection. Such sensitive strategies can also be used to discover novel disease biomarkers.
Nano-sensors for therapeutic drug monitoring: implications for transplantation
Aging, diseases and injuries can lead to organ failure that requires the transplantation of new healthy organs. the field of transplantation has witnessed a significant leap forward thanks to technological improvements. In addition to organs donated from healthy individuals, it is also
possible to transplant healthy organs from deceased donors. However, owing to organ shortage, many patients die every day waiting for organ transplantation. Therefore, tissue engineers have recently begun endeavoring to fabricate human tissues and organs to address the organ donor shortage. Successful human organ fabrication and implantation are limited, and have included flat, tubular and hollow nontubular organs such as skin, vaginas, blood vessels, urethras and bladders.
Therapeutic drug monitoring
In the 1970s, therapeutic drug monitoring was introduced to achieve the maximum therapeutic efficacy while reducing adverse events, which are critical aspects of optimal treatment. Therapeutic drug monitoring or clinical pharmacokinetic assessment include the measurement of drug concentrations for safe and efficient drug dosage adjustments; therefore, they play an important role in the treatment and management of many indications. The most important goal of therapeutic drug monitoring is to optimize the drug concentration and pharmacological response, which vary among individual patients owing to numerous involved factors. Usually, therapeutic drug monitoring involves the testing of blood samples to understand the effect of the drug. However, less invasive tests are also being developed using different biological mediums such as interstitial fluid, saliva, semen and urine. Among these biological matrices, interstitial fluid and saliva show the highest potential as alternative noninvasive candidates for blood tests. In many indications, real-time monitoring and, if possible, controlling the drug effect and therapeutic treatment are essential for the successful outcome of the procedure. For example, in personalized medicine, a tailored dosage of the drug is used for each individual patient based on age, sex and other personalized criteria.
During the course of organ fabrication using regenerative medicine and tissue engineering approaches, it is critical to monitor intratissue biological activities. Such monitoring must be noninvasive and help sustain vital tissue functions such as angiogenesis and cell signaling. To design such critical biosensors, bioanalyses related to cell and tissue integrity, as well as to microenvironment conditions, need to be considered. Factors to consider when determining such analytes include cell adhesion, growth and function as well as the concentration of fundamental minerals and gases such as oxygen. Other bioanalyses that are detrimental for cell and tissue health must also be monitored. Such unfavorable analytes may be produced owing to adverse cellular events such as oxidative stress, which can cause serious damage to cells, tissues and organs (including the nervous system), and can trigger numerous acute or chronic conditions such as Huntington’s, Alzheimer’s or Parkinson’s disease. Therefore, monitoring and controlling the levels of harmful molecules are critical for fabricating the final organ product. Furthermore, contamination and infection are significant obstacles that can impact the lengthy and expensive organ fabrication procedure. Consequently, biosensors that monitor for bacterial or viral contamination may be useful for tissue engineering and regenerative medicine applications. Combining nano-sensors with different bio-fabrication techniques may enhance the tissue fabrication; advancements in the science and technology of bioprinting can enhance the fabrication of nano-biosensors for more sophisticated and ambitious applications. Nano-sensors are employed in the therapeutic applications of stem cells to monitor their differentiation before transplantation. This technology allows the capability of monitoring cellular surface proteins and neurotransmitters and is useful for patients with Parkinson’s disease because they can confirm the differentiation of stem cells into dopamine-producing neural cells. The few examples of biosensing applications in regenerative medicine may introduce new strategies for monitoring and controlling the biological structures at the cellular level.
Figure 1: Biosensors to detect organ rejection.
Highly sensitive nano-sensors provide unique signal detection and amplification strategies to push the limits of detection of nano-sized concentrations. Such sensing capabilities can be extremely useful to detect biomarkers and to diagnose diseases early on or reoccurrence after a treatment. Examples for nano-sensor use include the detection of DNA damage, cancer, virus infections, cardiovascular diseases or Alzheimer disease. However, in many cases the usefulness of nano-sensors has yet to be proven in a clinical setting or even in clinically relevant samples.
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Even from this limited number of examples, it is evident that nano-sensing technologies have evolved considerably since first reviewed in this journal. Whilst the technology is still nowhere near mature, a growing number of developments are reaching a stage where commercialization is imminent. However, what we are seeing today is just the start; all manner of novel sensors will arise as new materials and fabrication technologies are developed, and new nanoscale phenomena are discovered.