The planet Earth is the only known biosphere for human beings; it is, therefore, of paramount importance for human health to protect and preserve this environment. For this, it is imperative to detect pollution sources, understand contaminants and the effects these substances may have on our body after both short and long-term exposure (or in other words, to understand acute and chronic toxicity). There are various particles, chemicals, and gases that influence the quality of the air we breathe. Incomplete combustion of coal, diesel, or other fossil fuels, can lead to the formation of cancerogenic substances. While providing numerous useful and versatile compounds in high amounts, such as plastics or novel chemicals, the corresponding industry often introduces these materials without prior testing for the long-term effects on the environment and human health. One notorious example for the unintentional introduction of hazardous particles by the industry is the fabrication and further incorporation of asbestos into building materials [1
]. Similar scenarios occurred with many chemicals that are classified as volatile organic compounds (VOC). More recently, the advent of nanomaterials helped to create many novel materials and to improve the properties of already existing ones. These materials include, but are not restricted to, carbon-derivates, organic and inorganic nanoparticles, 2D-materials such as graphene, and others. Here, not only the chemical composition, but also the size and shape of the nanomaterial, all have an impact on human health. These novel materials, before being released for public use, and thus, into the environment, need to be tested for their toxicity. This includes time and cost-effective physiochemical analysis of different pollutants, and subsequent investigations on possible health risks. In this context, recent advances in fabrication techniques might contribute, as they allow for the miniaturization of sensors and detectors, and the design of organ-like in vitro systems.
The advance of microelectromechanical systems (MEMS), a basis for the fabrication of microchips, was initiated by the need to concentrate many functional structures within a small area [2
]. The micrometer- and even nanometer-sized structures are made by different techniques, such as photolithography, injection molding, embossing, etching techniques, or 3D printing [3
]. For the fabrication of MEMS, different materials such as silicon, metals, ceramics, or polymers can be used. The applications for the MEMS devices range from ultrasound transducers [4
] and Lab-on-Chip (LoC) [6
] to rather sophisticated Organ-on-Chip systems (OoC) [7
]. Usually, the chip itself represents the core of a given system, while the accompanying peripheral instrumentation setup can be much larger. For example, in air quality sensors, samples of air are first taken and then delivered to the chip component of the setup. The particle size and chemistry is then determined on the chip, providing an immediate readout. Similarly, cells ranging in numbers between one and a few hundred to thousands can be deposited and examined using MEMS technology. Here, the chip is part of a setup that usually involves a microscope, fluid control, and sensors, with their corresponding electronics, needed to deliver the readout of interest. For most portable devices, the chips are optimized towards an increase in energy efficiency. There are countless possibilities to utilize LoC and OoC systems. The established technologies already allow for fabrication and subsequent application, and are robust enough to be used in extraterrestrial space, for example in satellites [8
]. For the use in space, MEMS allow minimizing various components down to a size range of a few micro- or nanometer-microsensors, actuators, accelerometers, heat controllers, microfluidic thrusters, microwave devices, satellite communication, and others. This facilitates the development of highly reliable, economical and mass-produced satellites that might also be used for monitoring pollutant sources, such as dust storms or volcanic activity [9
]. On the ground, LoC systems offer an unprecedented sensitivity in the assessment of small particle characteristics or the detection of chemicals. For example, hazardous particles in the air, which can originate from pollution sources, can be assessed by the right type of device [10
]. Nowadays, it is not uncommon to access the readouts of the closest air monitoring station through a respective online portal. The readouts are determined and immediately provided in real-time (Figure 1
]. The air monitoring stations cost from several hundred to tens of thousands of dollars, and are usually affordable for cities with a population of over one hundred thousand people [12
Conventional 2D cell culture, although of immense value in past research, is strongly limited in recreating tissue-specific parameters, such as pH, pO2
, extracellular matrix composition, or the presence of mechanical forces. Thus, the translation of data gained in conventional cell culture into complex organisms is hampered, a disadvantage that is apparent in many fields, such as regenerative medicine or toxicology. To compensate for these shortcomings, animal experiments are widely used, especially in the risk assessment or testing of chemicals and novel drugs. Yet, the species-specific differences between test animals and humans make a direct translation of results difficult [13
]. One possible way to overcome these shortcomings is the use of OoC systems. Here, microfluidic platforms or chips are used to recreate a physiological environment that resembles the specifics of the tissue of interest, and also allows the co-culture of different cell types in 2D or 3D [15
]. In addition, the connection of several different organ-models on one platform was proposed, a concept dubbed multi-organ or body-on-a-chip. OoC systems, like functional Lung-on-Chip, Heart-on-Chip, Kidney-on-Chip, Liver-on-Chip and other OoCs are readily available, and funding in this area of research is increasing (Table 1
]. These developments raise big hopes, as they allow for low-cost testing of drugs and chemicals, while physiochemical and cellular parameters of the tissue of interested can be recreated, therefore increasing the predictive value of the OoC. Recent lung-on-a-chip systems allow for testing airborne particles and substances for their toxicity on various cells in a monolayer or as 3D cell aggregates [17
]. One example of such an approach is the smoking small airway-on-a-chip where a device that mimics human smoking is connected to a lung-on-a-chip to induce and investigate pathological phenotypes caused by inhaling cigarette smoke [18
In this review, we want to provide an overview on air pollutants, including their sources and accompanied health risks due to exposure. Furthermore, the usage of LoC and OoC devices in the context of air quality assessment and health risk investigation will be discussed.
2. The Air We Breathe
Over the Earth’s history, the atmosphere’s gas composition has changed considerably. Already some 3.5 billion years ago, photosynthetic archaea and bacteria started to produce oxygen (O2
), resulting in a significant accumulation in the Earth’s atmosphere within the last two billion years [19
]. In the course of this vast time frame, the oxygen level rose up to 35% by volume [20
], compared with 21% today. Since the last peak of oxygen (the last 300 million years to the present), the Earth’s atmosphere has retained an almost constant composition [21
The composition of air that is considered as clean consists mainly of three gases and some water vapors. Besides the three main air components, nitrogen (N2
, 78.084%), oxygen (O2
, 20.964%), and carbon dioxide (CO2
, 0.0407%), there is a small percentage of other trace gases in the air, such as argon (Ar), neon (Ne), helium (He), hydrogen (H2
), krypton (Kr), nitrous oxide (NO2
), ozone (O3
), and methane (CH4
]. The amount of water vapor may occupy 1% of the air at sea level, or even up to 5% by volume in humid and hot environments. Additionally, the air contains some other aerosols, such as colloids of fine solid particles or liquid droplets. These aerosols may originate from non-anthropogenic sources (such as sea salt, pollen, spores, dust), or from anthropogenic activities (such as cigarette smoke, fumes in car exhaust, industrial air pollution, etc.).
4. Emerging On-Chip Technologies for the Air Quality Measurements
On-chip technologies enable the creation of fast, precise, simple, portable, low-cost gas sensing platforms with wide application areas, including air quality monitoring [127
]. The most widely known electrochemical sensing principles, based on charge generation or conductivity changes, are already available on the market and implemented as on-chip products [129
]. At the same time, gas sensors based on MEMS technology are superior to other sensor types regarding selectivity, decreased power dissipation, lower operating temperature, and quicker response. Moreover, some of the “pure” MEMS sensor elements, such as bridges, cantilevers, membranes, etc., can be fabricated by the well-established complementary metal-oxide-semiconductor (CMOS) technology [2
]. This provides unmatched opportunities regarding technology advances and price lowering for the integration of the sensing chips with microelectronics, and even allows for the co-fabrication of electronic circuitry and sensor architecture.
Using MEMS structures for air quality sensing means that gravimetry needs to be employed in one way or another [130
]. Gravimetric on-chip detection can primarily be used to sense comparatively larger particles in the gaseous environment: dust, microparticles, nanoparticles, and aerosols and liquid microdroplets trapped within the mechanical structure. Also, recent developments demonstrate the suitability of gravimetric principles for highly selective sensing of low molecular weight gases, such as CO2
]. MEMS gas sensors deliver the promise of higher sensitivity, as they are more selective in distinguishing between various gases. Their advantages are demonstrated by reports of a reached sensitivity of 4 Hz/ppm for CO2
by using capacitive ultrasound transducers (CMUT) type sensor [132
]. More convenient metal oxide electrochemical sensors have a detection limit in the range of hundreds of ppm for CO2
, and for this, require elevated temperatures [133
Gravimetric sensing of gas molecules requires the development of a functional layer, which selectively binds or adsorbs gas molecules. A primary example of a gravimetric detection principle is quartz crystal microbalance, which provides mass detection by analyzing changes in the resonance frequency of a crystal induced by the presence of certain molecules on the surface of the crystal [135
]. The common readout solution for this sensor type is to connect the crystal as an electromechanical resonator to an oscillator circuit. This provides the possibility for efficient, low noise, and compact detection [130
]. Besides, of classical implementation of the gas sensing MEMS, which are based on piezoelectric materials, there is no requirement for piezoelectric properties of materials for the resonance MEMS, based on cantilevers [137
] or membranes [131
] that allow for a capacitive readout. Moreover, some of the CMUTs feature vacuum-backed membrane structures and therefore are advantageous because of potentially higher working frequencies and higher resonance quality compared to other MEMS structures, which do not have vacuum-backing. Better resonance quality provides sharper frequency pointerand makes lower frequency shifts detectable, while higher oscillation frequency is important, because the absolute frequency shift is greater at higher resonance frequency for the same added mass [131
], so the sensitivity potential is greater.
Nevertheless, the need for materials that specifically bind the molecules of specific gases to the surface slows down the development of gravimetric sensors. For example, there are only a few candidates to establish the functional layers for CO2
], and only limited progress regarding MEMS-based gravimetric sensing of other hazardous gases, such as NOX
, or VOCs. Electrochemical sensors utilizing conductive polymers [140
], metal oxides, their combinations, and nanowires [142
] represent proven technologies for the sensing of these gases. Commercially available electrochemical on-chip sensor technology is based on a catalytic action, often driven by auxiliary temperature. The micro-hotplate and micro heaters solutions, partially using advantages of MEMS fabrication technology, were proposed to lower the energy demands for these catalytic sensors [144
]. This class of gas sensors still suffers from stability and degradation issues [145
], and still needs improvements regarding their energy efficiency [146
Our body is in direct interaction with the air that surrounds us from birth until death. Throughout our entire evolution, humans have learned to cope with natural pollution sources, such as salt spray from the oceans, dust storms, wildfires, volcano eruptions, etc. Usually, natural pollution sources are temporal and do not last very long (such as wildfire), or are seasonally reoccurring (such as dust storms). Although natural pollution produces rather small particles [79
], which can be more deeply inhaled into lungs, and are therefore more dangerous, the natural pollutants are overall less toxic, regarding their chemical formula, compared to those of anthropogenic origin.
Anthropogenic pollution affects the air quality both indoors and outdoors. Here, burning fossil fuels can be regarded as the main source of pollutants. Aside from SO2, NOX, and other exhaust gases, there are many anthropogenic pollution formulations, such as POPs, that are persistent, and thus will affect our environment in the long-term.
Of course, it is of high importance to identify sources of pollutants and to follow their migration patterns. On the global scale, large area sand storms, industrial gases, and other pollutants can be monitored with the help of satellites. Satellites can be equipped with various sensors, capable of detecting and quantifying the size and chemistry of particles. For example, a moderate resolution imaging spectroradiometer (MODIS) is used to gather information on various gases, including formaldehyde (CH2
]. On the ground level, the air quality in many cities is monitored with the help of meteorological stations. The data can be accessed in real time online; mobile phone applications are also available. For example, The World Air Quality Index project provides information from more than 70 countries by collecting and summarizing air pollution data from 600 major cities with more than 9000 stations in total (Figure 1
Indoor air can be monitored for various pollutants, such as CO2
and VOCs, while conditioning systems can be adjusted to improve air quality. Additionally, the air inside houses or cars can be filtered through various filters (such as a High efficiency particulate air (HEPA) filter). There are many tools to monitor and improve air quality. The best solution is to understand the source of a particular pollutant and minimize its output. There are many examples of new and untested materials being introduced to our environment prematurely, and only in later steps, their hazardous potential is recognized, eventually leading to their complete ban. That happened with asbestos, which was popular until 1975 [61
], POPs [91
], and others. Now, there are worldwide regulations in place, including a total ban on these substances. We predict the same may happen to the burning of coal and diesel fuel, as these fuels produce cancerogenic particles in the nanoscale size. We observe the constant progress towards a cleaner environment, fueled by the demands of an ever-increasing number of educated and concerned citizens who exert pressure on policy-making authorities. For example, in China, there are currently very few personal vehicles using diesel, with increasing popularity of silent and clean electric-powered cars and scooters.
Small detection chips are gaining popularity in sensing various gases, particle size, and chemical composition of the air. These chips are small, cheap, and can be included in mobile stations to provide data in real time [129
]. Advances in MEMS and CMOS technologies allow for the utilization of gravimetric on-chip detection for CO2
and, with limitations in detection sensitivity, for NOx
, or VOC gases [140
]. New materials, such as a combination of metal oxides, nanowires, or conductive polymers, allow for the development of novel electrochemical sensors [143
]. There are still some issues with stability and energy requirements, which we expect to be solved by using microheaters in combination with other technologies [145
Aside from their overly negative effects on the environment, airborne pollutants pose a major hazard to human health. Our body is in constant contact with air. The main routes of exposure resulting in health risks are through the dermal (skin) or respiratory systems. The particle chemistry, size, and shape, have a major impact on the hazard a particular pollutant poses. The particulate matter PM2.5 and nanoparticles are especially dangerous, as these particles are capable of entering our blood stream, from where they may reach other organs [111
]. Burning of incense in religious rituals, but also, burning agarwood (oud) produces smoke that people find pleasant and relaxing, despite the small particles present in the smoke. This phenomenon needs more investigation, as the continuous breathing of these special scents may even stimulate the immune system [177
Gases like CO, CO2, and VOCs may affect the brain, causing headache and fatigue. PM2.5, O3, SO2, and NOx affect the lung, causing respiratory pathologies. SO2 and NOX additionally can cause cardiovascular illness. VOCs lead to skin irritation, cause nausea, and increase the risk of developing cancer. Various bacteria, parasites, and chemicals carried by dust particles may promote asthma and cause allergic reactions.
In particular, the pollutant effects are evident only after long-term exposure, and are difficult to recreate in conventional cell culture [108
]. Here, OoC technology might help to bridge the gap between in vivo observations and in vitro experiments. For example, cancer formation utilizing human cells can be simulated on the OoC within weeks, while cancer formation after the exposition of the body to pollutants usually takes months to years.
It is obvious that air pollution will remain an important issue in the future. Microchip technology will gain more impact in the field of air monitoring, so that the pollution sources can be detected early, and exposure of humans can be minimized. We expect that substances proved to be a hazard to human health (such as asbestos, POPs, etc.) will be soon be completely banned worldwide. There are many new substances, including anthropogenic nanoparticles and novel polymers being developed and supplied to our market. Novel materials are always potential pollutants, and should be tested for their effect on organs and tissues by progressive utilization of OoC technology, instead of solely relying on animal testing and conventional cell culture experiments. This would enable better estimates on the toxicity of novel materials on human cells. Additionally, the chip technology can be used for the detection of various illnesses and cancer types. For example, more research is needed to detect and treat cancer early. OoC are very handy in here—human cells can be grown under various conditions and supplemented with different available pharmaceutical drugs, novel ones or their combination.
While humans are responsible for the anthropogenic activities and have the biggest impact on our shared biosphere, we would like to point out that all life forms are affected by the biosphere pollution. It is, therefore, our responsibility to minimize environmental pollution.