Magnetic Fields in Biotechnological Processes Using Eukaryotic Organisms: History
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Despite the growing prevalence of using living organisms in industry, the control of biotechnological processes remains highly complex and constitutes one of the foremost challenges in these applications. The usage of electromagnetic fields offers a great opportunity to control various biotechnological processes by alternating growth and cell metabolism without influencing the characteristics of the cultivation medium or the products of the biotechnological process.

  • electromagnetic field
  • biotechnology
  • microorganisms
  • metal

1. Control of Biotechnological Process

Nowadays, the usage of living organisms in industrial applications is a welcomed environmentally acceptable alternative to some industrial methods and chemical synthesis processes. The importance of bacterial technologies in the pursuit of sustainable industrial processes is undeniable [5,6]. Incorporating living organisms into industrial processes not only offers environmentally friendly alternatives and the potential for long-term sustainability, but also addresses the persistent challenge faced by today’s industries of controlling biotechnological processes. Despite the undeniable advantages of biotechnologies, such as their environmentally friendly approach, low cost, substrate flexibility, and low or lack of waste production, etc., the control of biotechnological processes remains challenging for industries today [4]. The main reasons for this are illustrated in Figure 1.
Figure 1. The challenges of biotechnology process control.
  • Complexity of biological systems: Organisms commonly used in biotechnological applications are complex biological systems; therefore, it is difficult to predict how specific changes in the environment will affect the organism at multiple levels, and even subtle changes can lead to inconsistent outcomes or alterations in the quality or quantity of the resulting product [6].
  • Variability: Biological systems used in biotechnology include bacteria, fungi, plants, as well as higher organisms. Therefore, a uniform method of controlling processes is impossible, and each biotechnological application, along with each organism used within it, requires specific conditions for the optimal growth and production of the target product [7,8].
  • Nonlinear dynamics: Biological systems often exhibit nonlinear dynamics, meaning that small changes in one part of the system can have disproportionately large effects on the overall behavior of the system. This effect can make it difficult to predict how a biotechnological process will respond to changes in external or internal parameters [9,10].
  • Lack of knowledge and up-scaling difficulties: Despite advances in biology, much remains unknown about how biological systems function and precisely respond to changes in the environmental conditions at the physiological or genetic levels. This can pose challenges in designing and controlling biotechnological processes with a high degree of precision [3]. It is important to ensure that the process can operate at larger volumes without losses in the efficiency or product quality [11].
  • The price: Biotechnological processes used in certain industries, such as the pharmaceutical industry, may be less cost-effective compared to traditional industrial processes [12]. Furthermore, these processes often require specialized equipment to provide the optimal conditions for the used organisms, which can further increase their costs [13]. Seeking cost-effective strategies for the control of biotechnological processes is one important approach for making biotechnological processes more accessible and competitive [14].
  • Time: Certain biotechnological processes, such as protein or metabolite production using microorganisms, bacterial bioleaching, and microbial waste treatment, can, in some cases, be slower compared to conventional processes [5]. This can pose a challenge for the industrial implementation of these biotechnological processes, which often require large quantities of a product in a short period [4].
  • Ethical and safety concerns: Ethical and safety considerations still exist and must be taken into account when working with biological systems. The potential risks and unintended consequences of biotechnological processes can be subjects of public concern, which can present challenges in balancing the benefits of a particular process with its potential risks [15].
  • Extensive industrial application of biotechnology: The use of living systems is not limited to a single industry but can be found in nearly every sector, from healthcare to environmental remediation and waste processing [16]. Since each of these industries uses different organisms and produces different target products, they require a varying process control complexity and face different challenges [17].

2. The Application of Magnetic Fields in Biotechnological Processes Using Eukaryotic Organisms

Notably, research has revealed that magnetic fields possess the potential to expedite specific processes, as exemplified by enhanced ethanol production and plant-based phytoremediation. Beyond these applications, the influence of magnetic fields on human immunity and their potential employment in medical treatments have also emerged. These sectors are intricately detailed in the subsequent subsections to allow a comprehensive understanding.

2.1. The Food Industry and Ethanol Production

Saccharomyces cerevisiae is the most well-known microorganism involved in ethanol production and has been used in fermented beverages for centuries [34,35]. Under anaerobic conditions, S. cerevisiae utilizes pyruvic acid derived from sugar catabolism, which is converted via acetaldehyde into ethanol. A total of 12 enzymes are involved in the fermentation process. However, the two key enzymes in the yeast fermentation pathway are pyruvate decarboxylase and alcohol dehydrogenase, which regenerate NAD+ and produce ATP [35]. The choice between the aerobic and anaerobic glucose degradation pathways is genetically encoded and relies on gene repression induced by the Crabtree effect, which modifies the respiratory chain of the Krebs cycle and switches glucose metabolism to an anaerobic process that occurs in the cytosol instead of aerobic metabolism in the mitochondria [30]. The alcohol fermentation process spontaneously ends when the ethanol concentration in the medium reaches approximately 14 to 20%. Such high levels of ethanol have an inhibitory effect on the yeast cells that produce it. The inhibitory effect of ethanol lies in changes in the organization and permeability of the cell membrane and the deactivation of cytosolic enzymes [31]. During industrial alcohol fermentation, it is crucial to maintain yeast cells in a reproductive (budding) state and to avoid stressful conditions that could jeopardize their growth [36].
In the study of the influence of a magnetic field on the fermentation process, Perez et al. [29] observed the positive effect of extremely low-frequency magnetic fields with a magnetic induction of B = 5–20 mT on ethanol production. The conditions with a magnetic field of 20 mT showed the best results, with the total ethanol productivity being approximately 17% higher than in the control experiment. There was also a difference in the fermentation time, as the yeast exposed to the magnetic field reached its final stage approximately 2 h earlier than the control experiment.
The effect of a magnetic field (permanent magnet, 220 mT) was also studied by Da Motta et al. [30]. The authors documented a 3.4-fold increase in the ethanol concentration compared to the control culture. Glucose consumption was also higher, correlating with the ethanol yield. Even after 24 h, the yeast exposed to the magnetic field continued to proliferate intensively, despite the high alcohol content, unlike the control culture. Alcohol production in magnetized cultures steadily increased from the fourth to the twenty-fourth hour, resulting in a production rate 1.68 times higher than in cells not exposed to a magnetic field.
Anaerobic alcohol fermentation is known to be directly related to the production of gaseous CO2 and increased biomass production [37]. Therefore, the authors hypothesized that the mechanisms of ethanol-to-glucose conversion are likely influenced by the static magnetic field, as the glucose/ethanol/biomass conversion rate in cultures exposed to the magnetic field was higher than in the control.
In contrast to the positive results with static and low-frequency magnetic fields [29,30], the rotating magnetic field alone was not able to increase ethanol production [31]. An increase in the fermentation rate was observed only in combination with a magnetic field (amplitude: 1 mT, f = 100 Hz) and magnetic particles in the medium, resulting in a 50% increase [31]. These different observations confirm the assumption that the type and strength of the magnetic field significantly influence the resulting biological effect on living organisms [38].
In addition to its impact on the alcohol product itself, there is a possibility of using magnetic fields to regulate the content of mycotoxins present in plant-based fermentation substrates using S. cerevisiae yeast, which has the ability to degrade certain contaminants during fermentation through the activity of specific yeast enzymes [39]. These enzymes are involved in cellular physiological processes related to protection against oxidative stress and detoxification [40], and their activity can be enhanced by the application of a magnetic field [41]. Therefore, alcohol fermentation with S. cerevisiae holds promise as a method for reducing the mycotoxin content [39]. However, Boeira et al. [33] did not observe a significant change in the mycotoxin concentration after the application of a magnetic field (35 mT) to the fermentation process. The potential of magnetic fields to aid in the removal of fermentation contaminants has been the subject of only a small number of studies, and more attention should be given to exploring this issue in the future.
Improving the fermentation capabilities of selected fungi is another area of research where magnetic fields have the potential to be used to enhance biomass production and the production of specific enzymes. Canli et al. [32] investigated strains of Geotrichum candidum and its fermentation capabilities. In their experiment, they significantly increased the enzyme activity of inulinase and biomass production through the application of a static magnetic field of 7 mT. Based on these results, the authors considered the magnetic field to be an effective method for increasing the production of specific products by various fungi.

2.2. Medical and Laboratory Applications

Magnetic fields can be also used as an adjunctive therapy for the treatment of certain diseases, but the most studied remains the auxiliary medical procedure for cancer treatment. Recently, the use of circularly polarized magnetic fields has been investigated to enhance the immune response by increasing tumor cell death and accelerating the maturation of dendritic cells and the infiltration of T-lymphocytes in the tumor [42]. Furthermore, the combination of magnetic-field-induced hyperthermia and the integration of nanoparticles containing anticancer drugs has been studied. Clusters of Fe3O4 nanoparticles generated heat upon electromagnetic field application, leading to the release of doxorubicin. According to the authors, this combination has the ability to destroy cancer cells and achieve a complete cure without malignancy recurrence [23]. Increased levels of cell death have also been observed by other researchers studying electromagnetic fields (50 Hz) modulated by a static magnetic field (5.1 mT). The more frequent occurrence of apoptosis and ferroptosis is attributed to the induction of reactive oxygen species (ROS) and significant DNA damage, as well as the activation of DNA repair pathways. This combination of magnetic field effects had an inhibitory impact on the population of cancer cells [19].
Magnetic fields have also been studied in relation to patient immunity. The exposure of M1 pro-inflammatory macrophages to non-uniform magnetic fields causes extreme elongation of macrophages and the acquisition of an anti-inflammatory M2 macrophage phenotype. This transformation depends on the position relative to the magnetic field lines [22].
Other applications of magnetic fields can be to accelerate wound healing [20,43] or as an adjunctive treatment for arthritis [44], as well as to initiate the differentiation and migration of stem cells [45]. In the past, the abilities of electric, magnetic, and electromagnetic fields to aid in wound healing and associated inflammatory processes have been studied [46]. Some studies also highlight the effects of electromagnetic fields and their use in tissue regeneration. It has been found that frequencies and intensities of pulsed electromagnetic fields in the range of <100 Hz and 3 mT have positive effects on accelerating wound healing processes [47]. Clinical studies in humans have also demonstrated that electromagnetic fields reduce the healing time and recurrence rate of leg ulcers [48] and may have anti-inflammatory effects [21].
In addition to the direct use of magnetic fields in medical therapy, the application of orthogonal electric pulses with durations of 0.1–2 ms and field intensities of 2.5–4.5 kV/cm to a yeast suspension led to the release of cytoplasmic proteins without cell lysis, which aided in protein extraction. Treated cells were more susceptible to enzymatic cleavage. Depending on the strain and electric conditions, cell lysis was achieved at a 2- to 8-fold lower enzyme concentration compared to the control. These findings could be useful for the efficient isolation of proteins from cells without complete cell lysis [49].

2.3. Pollutant Removal

Soil remediation is another potential but underexplored area where magnetic fields could be applied as a low-cost biotechnological enhancement. Compared to the fields used in yeast and prokaryotic organisms, the fields investigated in plants are much higher (100–400 mT), and lower fields have been deemed to be insufficiently effective.
Several studies have observed the beneficial effects of magnetic fields on the phytoremediation process of metal-contaminated soil. The results show that the application of magnetic fields improves the soil remediation efficacy with a significantly reduced total Cd content (38.9%) and bioavailable Cd content (27.3%) in the soil. Additionally, the Cd content in two types of rice grains was significantly reduced [50]. Further research has demonstrated that plants grown from magnetic field pre-treated seeds have the ability to accumulate 28.8–250.1% more metals (Cu, Cd, Hg, Pb, Zn, Cr) [24,25]. The authors consider the best conditions for enhancing phytoremediation to be 120 mT for Noccaea caerulescens and 150 mT for Eucalyptus globulus [25] and 100 mT for Celosia argentea [26], which exhibited the greatest increases in biomass and accumulated metals.
For E. globulus and N. caerulescens, a magnetic field strength of 400 mT was found to be inhibitory in terms of biomass production as well as for the accumulation of present metals [24,25]. According to Yang et al. [26], a magnetic field strength of 30 mT is insufficient to affect the phytoremediation process using Celosia argentea.
In terms of economics, the costs associated with phytoremediation are related to the need for irrigation of the used plants. Prolonged drought can affect the transpiration rate and the efficiency of Cd extraction from the soil, inducing oxidative damage in plant cells. Yang et al. [26] reported that pre-treating seeds with a magnetic field helped plants to overcome 3- to 10-day drought periods and had a positive impact on the phytoremediation process, biomass production, and pigment levels, thus alleviating the harmful effects caused by drought.
Another economic challenge is the harvesting of whole plants after the completion of remediation. Harvesting above-ground parts such as leaves and stems is considerably easier. Leaves, in particular, are the site of intensive cadmium accumulation in Festuca arundinacea. According to Luo et al. [27], irrigating the plants of Festuca arundinacea with magnetized water increased the biomass of aging and dead leaves, which then redistributed significantly higher amounts of Cd compared to a control (approximately 23.6% higher compared to the control). Based on these findings, it can be stated that treating seeds or whole plants with a magnetic field has the potential to become a novel economic strategy to enhance the efficiency of phytoremediation.
In addition to the direct influence on plants, an innovative approach using the symbiotic relationship between bacteria from wastewater and the microalga Scenedesmus obliquus has been proposed to improve wastewater treatment, along with the application of a static magnetic field [51]. The algae–bacterial symbiotic system can enhance the production of dissolved oxygen, thereby promoting bacterial growth and the catabolism of pollutants in wastewater. The results showed that the magnetic field (ranging from 50 to 500 mT) stimulated algal growth, increased oxygen production by 24.6%, and elevated the chlorophyll content by 11.5% compared to the control. The study confirmed that the application of an appropriate magnetic field could reduce the energy consumption required for aeration in the degradation of organic matter in municipal wastewater using the symbiotic system.

This entry is adapted from the peer-reviewed paper 10.3390/su151914459

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