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The significant advancements within the electronics miniaturization field have shifted the scientific interest towards a new class of precision devices, namely microelectromechanical systems (MEMS). Specifically, MEMS refers to microscaled precision devices generally produced through micromachining techniques that combine mechanical and electrical components for fulfilling tasks normally carried out by macroscopic systems. Although their presence is found throughout all the aspects of daily life, recent years have witnessed countless research works involving the application of MEMS within the biomedical field, especially in drug synthesis and delivery, microsurgery, microtherapy, diagnostics and prevention, artificial organs, genome synthesis and sequencing, and cell manipulation and characterization. Their tremendous potential resides in the advantages offered by their reduced size, including ease of integration, lightweight, low power consumption, high resonance frequency, the possibility of integration with electrical or electronic circuits, reduced fabrication costs due to high mass production, and high accuracy, sensitivity, and throughput. In this context, this paper aims to provide an overview of MEMS technology by describing the main materials and fabrication techniques for manufacturing purposes and their most common biomedical applications, which have evolved in the past years.
Keywords: MEMS, BioMEMS, lab-on-chip devices, microfluidics, microfabrication, diagnostics, drug delivery systems, microsurgery
The tremendous advancements in electronics miniaturization have led to the birth of a novel class of devices, namely microelectromechanical systems (MEMS) [1]. Originated from the United States, the MEMS acronym can also be referred to as Microsystems Technology in Europe and Micro Machines in Japan [2]. Precisely, the term MEMS refers to micrometer-scaled precision devices, which combine mechanical and electrical components to accomplish tasks that are normally carried out by macroscopic systems [2,3,4,5,6]. With a size ranging from several micrometers to several millimeters, MEMS devices are generally produced through micromachining techniques that have originated in the integrated circuit industry, with silicon being the main material for their manufacture [1,3,4,5].
Considering that in 1965 the IBM360 computer filled two large rooms, the level of miniaturization that we are witnessing today due to the tremendous realizations in the semiconductor and integrated circuit technologies is overwhelming [7]. Originally developed in the microelectronic industry, the first MEMS devices were commercialized in early 1980, when MEMS pressure sensors and accelerometers were widely applied in the automotive industry [3,8]. In 1995, Bergveld first introduced the possibility of large-scale equipment miniaturization for chemical analysis [9]. As MEMS devices are currently present in all aspects of the daily life (e.g., image [10], touch [11,12], distance [13], pressure [14,15,16,17,18], temperature [19,20,21], and humidity [22,23,24,25] sensors, microphones [26,27,28,29], gyroscopes [30,31,32,33], accelerometers [34,35,36,37], and magnetometers [38,39,40]), the worldwide MEMS market is expected to grow to $25 billion by 2022 ( Figure 1 ) [3,4,41,42,43].
MEMS market value forecast in billion US dollars by year. Reprinted from an open-access source [43].
The most common type of MEMS are transducers, either sensors or actuators, which convert one type of signal into another type of signal [3,44,45]. However, they can also be manufactured into cantilever or string forms, corresponding to single- or double-clamped beam-like structures, respectively [46]. The mechanism of the MEMS devices is based on energy transduction, and it involves the transfer of the information from the sensing unit to the controller, which will decide based on the control algorithm and further output the command to the actuating unit [45,47].
MEMS devices are highly advantageous, especially due to their small size, closely related to characteristics such as ease of integration, lightweight, low power consumption, and high resonance frequency [3,4,6,48,49]. Furthermore, MEMS offers the possibility of integration with electrical or electronic circuits, which increases their performance and makes them ideal candidates for self-powered and wearable electronics [3,50]. Other advantages include reduced fabrication costs due to high mass production and high accuracy, sensitivity, and throughput [4,6,48,49]. However, there are still some challenges regarding their manufacture, as MEMS devices are small, fragile, and sensitive and, thus, are subject to cracks, bending, or decalibration of the moving parts [51]. Additionally, due to complex mechanical geometries, MEMS devices are predisposed to failure due to particle contamination, fatigue, fractures, stiction of rubbing or contacting surfaces, and wear [52].
Traditionally, MEMS were used for the production of sensors, switches, filters, and gears [5,8] integrated with microelectronic, radiofrequency, optoelectronic, thermal, or mechanical devices [53]. Currently, they are applied in a wide variety of fields, including aerospace, automotive, military [4], microfluidics, energy harvesting and storage, data storage [5,53], telecommunications [6], analytical biology, and chemistry, and biomedicine [1,6,8,49]. In the medicine and health care systems, MEMS devices, also known as bio-microelectromechanical systems (BioMEMS), micro total analysis systems (µTAS) [54,55,56], lab-on-chips (LoCs) [57,58], or biochips [59,60], could be potentially applied in drug synthesis, drug delivery, microsurgery, microtherapy, diagnostics and prevention, artificial organs, genome synthesis and sequencing [44,48], and cell manipulation and characterization tools [44,48,61,62].
In this context, this paper aims to provide an overview of MEMS technology by describing the main materials and fabrication techniques for manufacturing purposes and their most common biomedical applications, which have evolved in the past years.
The fabrication of MEMS devices involves the use of semiconductor elements [2,63]. Similar to the integrated circuit field, silicon has been the predominant material for the manufacture of MEMS devices [9,64]. Specifically, doped single crystalline silicon and polycrystalline silicon, also known as polysilicon, are the representative materials in the field, owing to their unique properties, including strength, conductivity, high resilience, no stress hysteresis, robustness during fabrication, performance reliability, easy processing, and good process reproducibility, and low unit costs [65,66]. Additionally, silicon can also be used in the form of silicon dioxide for insulation and passivation or as a sacrificial material, and silicon nitride for insulation [2,65]. Although it is abundantly found in nature, silicon has gradually become insufficient for the continuously growing functionality and complexity of MEMS.
Therefore, new materials have been increasingly included in the fabrication of MEMS, namely single-crystal cubic silicon carbide, germanium-based materials, such as polycrystalline germanium and polycrystalline silicon germanium, metals and metal nanocomposites (e.g., titanium thin films, gold, aluminum, nickel-iron, titanium-nickel), polymer materials (e.g., polyimide, SU-8, parylene, polydimethylsiloxane, cyclic olefin polymers, polymethylmethacrylate or plexiglass, polycarbonate, polystyrene, liquid crystal polymers), ceramics (e.g., lead zirconate titanate, barium strontium titanate, aluminum nitride, gallium nitride), and piezoelectric materials [2,65,67,68,69,70,71]. For the adhesive component, there are three common materials involved, specifically 2025D, 3140RTV, and SDA6501. 3140RTV and SDA6501 are soft adhesive materials that are preferred over the 2025D hard material due to better mechanical isolation against thermal deformation [66,72].
Polymers have been growingly replacing silicon, as they possess advantageous complementary properties, including flexibility, easy processing, insulation, chemical and biological functionalities, biocompatibility, and low cost. Moreover, mixing polymers with filler materials can form composites with desired electrical, mechanical, and magnetic properties [66,73,74]. The most common applications of polymers in MEMS include structural materials, substrates, adhesives, sacrificial layers, and functional coatings [51]. Among the previously mentioned polymers, SU-8, polyimide, and parylene are more compatible with the conventional microfabrication techniques and have been widely used as free-film substrates and structural elements on hybrid silicon polymer devices [68].
Recent years have also witnessed an increase in the use of glass, particularly borosilicate glass, as a material for MEMS fabrication. It possesses exceptional properties that are well suited for this technology, especially in terms of proper hardness for suppressing channel wall deformation, superior optical transparency, chemical, and biological inertness, surpassing optical transparency and insulating properties, high solvent compatibility, and the possibility of surface modification for facilitating liquid flow [75,76]. However, the manufacturing of glass microfluidic devices is significantly expensive and time-consuming, involving complex, multi-step processes that combine different techniques, tools, and equipment [77].
Piezoelectric materials are classified into inorganic materials, which include lead zirconate titanate, aluminum nitride, zinc oxide, barium titanate, lithium niobate, and quartz, organic materials, including polar polymers, such as polyvinylidene fluoride, and optically active polymers, such as poly-L-lactic acid and poly-D-lactic acid. Although piezoelectric polymers are more cost-efficient regarding material cost and processing, inorganic piezoelectric materials have an enhanced piezoelectric output [63].
Generally, electronics are fabricated through integrated circuit processing sequences, including metal-oxide-semiconductor processes or bipolar metal-oxide-semiconductor processes [78]. However, for the fabrication of MEMS devices, advanced technologies, processes, and materials are being used, as they require high-yield, affordable, and low-cost techniques to allow the development of 3D microscale structures [79]. The main technology for developing MEMS is semiconductor micromachining, which involves patterning through photolithography and etching for obtaining the required shapes [48,80,81]. Generally, patterning is the essential step in MEMS fabrication, which is performed through photolithography processes. Specifically, after exposing the light-sensitive polymer film-coated substrate to UV light, the polymer will change its solubility by becoming either more cross-linked if they are negative photoresists or less cross-linked if they are positive photoresists. The exposed areas are further developed away, resulting in a patterned film on the substrate [80,81,82,83].
The main techniques involved in the construction of MEMS devices are lithographic and non-lithographic technologies [79,80,84,85,86]. The most common techniques are lithographic, which further involve three major categories, namely bulk micromachining, surface micromachining, and LIGA techniques ( Figure 2 ) [79,80,84,85,86].
