The indication for performing a neck dissection in patients with differentiated thyroid cancers is metastatic involvement of the cervical nodes. Potential complications from lateral neck dissection include injury to the thoracic duct, cervical major vessels and nerves. There is a lack of review reporting the incidence of these complications and their diagnostic and therapeutic approach. Our review may help endocrine surgeons and clinicians to recognize and face up to these challenging problems.Neck dissection is a surgical procedure reserved for thyroid cancer cases with clinically evident lymphatic invasion. Although neck dissection is a reliable and safe procedure, it can determine a significant morbidity involving a variety of structures of nervous, vascular and endocrine typology. A careful pre-operative study is therefore essential to better plan surgery. Surgical experience, combined with accurate surgical preparation and merged with adequate and specific techniques, can certainly help reduce the percentage of complications. In recent years, however, technology has also proved to be useful. Its crucial role was already recognized in the safeguard of the integrity of the laryngeal nerve through neuro-monitoring, but new technologies are emerging to help the preservation also of the parathyroid glands and other structures, such as the thoracic duct. These surgical skills combined with the latest technological advancements, that allow us to reduce the incidence of complications after neck dissection for thyroid cancer, will be reported in the present article. This topic is of significant interest for the endocrine and metabolic surgeons’ community. Papillary carcinoma seems to be the most frequent tumor originating from the thyroid gland  and, eveIn order to lower the incidence of these complications, the extent of the lymphadenectomy was reduced, excluding portions II B and V A, allowing the risk, however, of a high incidence of recurrence ,10. An eComplications after neck lymphadenectomy for differentiated thyroid cancer can vary depending on the characteristics of the pathology  and factors associated to the technique . Complications of neck dissection for differentiated thyroid cancers are reported in In neck dissection surgery, many nervous structures can be involved and eventually damaged (scheme) although the most frequent injuries concern the lower laryngeal nerve .The surgical technique implies the identification and careful dissection of the nerve, but injury can also be caused indirectly by traction maneuvers or from the use of thermal energy devices. The intraoperative monitoring technique of the inferior laryngeal nerve is now practiced almost routinely and has been studied especially for benign thyroid surgery. Identification of the inferior laryngeal nerve is also possible.Currently, meta-analyses do not highlight a clear advantage of intraoperative neurophysiological monitoring (“IONM”) in reducing the incidence of nerve damage during total thyroidectomy . The conSpinal accessory nerve injuries vary according to the type of neck dissection performed (4.8–27%) and are more frequent in the case of dissection of levels II B and V A . The preThe anatomical knowledge of the course of the nerve with its variables, especially regarding the relationship with the deep jugular vein, is necessary for an accurate and thorough surgical preparation. It is in fact known that, in its proximal portion, the course (30%) of the vein is set anterior to the nerve, thus facilitating damages to the nerve itself, while, when set posteriorly to the nerve (70%), its isolation and traction on loops is facilitated. Moreover, in 96% of the cases, the spinal accessory nerve is oriented, at the level of the upper edge of the posterior section of the digastric muscle, laterally with respect to the internal jugular vein, in 3% it is medial to it and in 1% it passes through the vein itself .For the purpose of identifying the nerve, it is important to use IONM (with the contraction of the trapezius muscle), especially when treatment requires a dissection and clearing up of the level II B where lymph nodes lie above and behind the nerve .In this case, it is necessary to recognize the different subdivision pathways of the spinal accessory nerve in relation to the sternocleidomastoid muscle: in type 1 (66%), the branches for the trapezius muscle are located at the posterior edge of the muscle; in type 2 (22%), they are present before the nerve enters the muscle; in type 3 (12%), the motor branches for the trapezius muscle that were formed on the posterior border of the sternocleidomastoid muscle advance medially and fuse with the cervical plexus .The use of IONM allows the identification and preservation of the nerve which must be carefully isolated in order to avoid damage to the nerve and to its capsule also as this is often the cause of post-operative pain syndromes (shoulder and neck dysfunction) .Injuries to other nervous structures, such as the cervical plexus and the phrenic nerve, are extremely rare and can be avoided by identifying them and maintaining a superficial position in relation to the deep cervical fascia .Another possible use of IONM is the prevention of marginal mandibular nerve injury during neck dissection in cases where a level I B dissection and thorough clean-up is required .Hypoparathyroidism remains the most frequent complication after neck dissection for differentiated thyroid cancer. It can be temporary 23.2–51.3%), but the permanent form can reach important percentages (0.6–15.2%) [.2–51.3%,The extension of the surgical dissection up to level VI increases in its incidence , as doesInstead, the superior parathyroid glands, thanks to their more dorsal location, require less manipulation; therefore, they are less likely to be damaged. It is good practice, once the parathyroid glands have been identified, to perform afferent artery ligation near the thyroid capsule, avoiding the use of cautery. In addition, microsurgical magnifying eyeglasses can improve the quality of dissection. In case of impossibility to avoid impairment of the glands or their blood supply, they can be removed and after an intraoperatory histological examination, can be promptly re-implanted in the sternum cleidus mastoid muscle to start functioning in a few months. The performance of neck dissection with a “lateral” approach through the extra-thyroidal space has also been proposed .The development of technologies for the identification and preservation of the parathyroid glands is certainly useful in trying to reduce post-surgical hypoparathyroidism.Currently, there are two main techniques proposed, namely, near-infrared auto fluorescence  and indo® Fluoptics Grenoble France) light display system which is transmitted on a screen. It can also be useful in identifying inadvertently removed glands that need to be reimplanted.Intraoperative visualization of the parathyroid using near-infrared (NIR) light was first described at Vanderbilt University . The endAngiography with indocyanine green (ICG) was initially used for the diagnosis of macular degeneration. Later, it was used for the visualization of lymphatic structures, of the biliary tract and, more recently, to evaluate the vascular blood flow of intestinal anastomoses .An iodinated contrast medium with a half-life of 3–5 min is administered intravenously. It can be monitored through a near-infrared NIR emitter–detector camera system placed above the exposed glands that displays the arterial supply and venous drainage of the parathyroid gland.These new technologies seem to be able to improve the surgical strategy of recognition and preservation of the parathyroid glands.Thoracic duct injury is a serious complication of neck dissection. Fortunately, it is relatively rare (0.6–4.5%); although, when present, it is challenging and difficult to remedy . GeneralIntraoperatively, the abdominal compression maneuver can be useful. In addition to allowing a better visualization of the duct, it also helps to promptly identify and adequately treat a duct injury . Even inVascular injuries during neck dissection for differentiated thyroid cancer are minimal (0.5–1%). Anomalies of the great vessels of the neck are not very common and can be highlighted in the pre-operative instrumental study. The most common is the duplication and fenestration of the deep jugular vein which may be a site of surgical injury . While cLatero-cervical metastases are reported in 30–60% of patients with well-differentiated thyroid cancer . Their pThe pre-operative study is also important in the follow-up of patients who have already undergone surgery and in which recurrence can reach up to 29% . The nerIn recent years, the use of intraoperative neuromonitoring has become increasingly widespread with the aim to reduce the incidence of nerve injuries. This method is used mainly in benign surgery and the results are discordant. Shuwen et al., in their systematic review, report a slight benefit from the use of IONM without reaching statistically significant values . The resIONM is especially useful in the case of subdivision of the branches directed towards the type 2 trapezius muscle structure; that is, before the nerve enters the sternocleidomastoid muscle. It is near the posterior triangle where nerve injury is most frequent, especially if it runs superficially to the vein . A relevThe other nerves  are rarely the site of injuries, and their identification is facilitated by the anatomical respect of the deep cervical fascia. In the rare case of necessity of level 1b dissection, IONM may be useful to avoid injury to the marginal branch of the facial nerve . TransieSome technological innovations aiming to better identify and preserve the parathyroid glands have been proposed, for instance the near-infrared autofluorescence  and the Kahramangil et al. compare the two techniques and demonstrate an equivalent high percentage of gland identification . InsteadProspective studies and large numbers are required in order to reach reliable conclusions. Thoracic duct injuries are not frequent but when they occur, they are difficult to remedy. As we know, the thoracic duct must be identified when dissecting level IV lymph nodes on the left side, where it flows into the deep jugular vein after passing behind it. The abdominal compression maneuver can certainly make it more evident as can the use of indocyanine green near-infrared lymphangiography . In ordeLateral neck dissection is recognized as a valid procedure in the local management of differentiated thyroid cancer metastases. This type of surgery is indicated only in cases of clinically detectable metastases given that, in relation to other parameters, it seems to improve the survival rate of these patients. Neck dissection is burdened by a high rate of complications, even in the presence of a proper surgical technique, that can affect glands, vases and nerves. In order to reduce the incidence of these complications, less extensive lymphadenectomies have been recommended, so we outline a functional neck dissection and a selective neck dissection. The downside of this type of lymphadenectomy is the high number of recurrences, which often require re-operation. Therefore, an accurate pre-operative study is necessary in order to accurately identify the extent of the disease and thus plan the most suitable type of lymphadenectomy.The correct surgical technique involves the knowledge of the relationships between the structures and their possible anatomical variations. Even if the surgical procedure is carried out correctly, the rate of complications still remains high. In recent years, several technological innovations have been proposed to reduce these complications. Neuro-monitoring and parathyroid fluorescence definitely represent a very interesting novelty. These methods are constantly updated and must necessarily be validated with prospective studies based on significant case histories. To conclude, we can state that the possibility of reducing the incidence of complications after neck dissection for differentiated thyroid cancers will certainly rely on a correct surgical technique, and will increasingly make use of new technologies. Moreover, given that there is a lack of literature about this topic, we hope that the present work may give an insight about improvements in surgical technique and technology to help endocrine surgeons in avoiding complications during lateral neck dissection.


Lessons learnt from the initial stages of the COVID-19 outbreak indicate the need for a more coordinated economic and public health response. While social distancing has been shown to be effective as a non-pharmaceutical intervention (NPI) measure to mitigate the spread of COVID-19, the economic costs have been substantial. Insights combining epidemiological and economic data provide new theoretical predictions that can be used to better understand the health economy tradeoffs. This literature review aims to elucidate perspectives to assist policy implementation related to the management of the ongoing and impending outbreaks regarding the Health Economic Dilemma (HED). This review unveiled the need for information-based decision-support systems which will combine pandemic spread modelling and control, with economic models. It is expected that the current review will not only support policy makers but will also provide researchers on the development of related decision-support-systems with comprehensive information on the various aspects of the HED. The emergence of the novel Coronavirus disease COVID-19) in December of 2019 in Wuhan, China has rapidly left a significant dent on the global community. As of 9 December 2020, the pandemic has impacted 191 countries with over 68 million global cases confirmed and over 1.5 million deaths 9 in Dece. The high virulence and transmissibility of the virus, and the lack of effective drugs, antivirals and vaccinations threatened the inundation of health systems in heavily stricken regions and made “flattening-the-curve” of infections a top priority ,4,5. TheThe implementation of interventions to “flatten the curve” during the ongoing pandemic characterizes the high societal prioritization of public health and its primary focus during the COVID-19 outbreak among most world leaders and decision makers ,13. ThesFor the World Health Organization (WHO), a key global player in public health outbreak response, the declaration of a PHEIC during the COVID-19 outbreak presented an opportunity to identify what is subject to mandatory reporting by WHO country members as part of the International Health Regulations (IHR) revisions that were adopted in 2015 . ThroughAs extraordinary mitigation measures were directed by decision-makers, the intensity and far-reaching impacts on additional societal domains of life and segments of society became apparent rapidly ,20,21. TAmidst the impacts of the disease on mortality and morbidity, the global economy has also encountered substantial adverse disruption. To date, the outbreak has occasioned the largest downturn since the financial crisis of 2008 and a general downward trend in the global economy triggered the worst global recession since World War II . The IntIn light of this, of a particular interest for this systematic review is the consequential intersection between the public health and economic domains as well as the underlying costs to each domain which are critically contingent on the measures taken. For decision makers, precisely the aforementioned interaction, or what is hereby referred to as the health-economy dilemma (HED), has proven to be a substantial challenge. The nature of the debated tradeoff of the HED examines both local and global issues. For example, the effect of NPIs  on infectivity levels versus the incapacity of households to maintain their income. On a global scale, the HED touches on issues such as the impact of international border closures on curbing spread of the virus versus its influence on service-oriented economies (particularly those that are largely reliant on tourism) such as Greece, Portugal and Spain .While inaction was not a feasible option for all but few authoritarian countries, many governments deliberated the optimal strategy for containment of the virus. Opportunities for lessons learned from past similar events have been constrained by the low incidence of global pandemics in history and the novel challenges posed by an increasingly globalized world. In addition, the endless combinations of NPIs, the distinct circumstances of each country and the complexity of pattern predictions of a novel pathogen, all added to the difficulty of the task. Countries struggled to strike a balance between the two domains, attempting to simultaneously flatten the infection curve and the “macroeconomic crisis curve” .The COVID-19 outbreak and its consequent economic implications have driven a surge of peer-reviewed publications and gray literature by scholars, think tanks, policy institutions and international organizations, integrating economic theory with epidemiological models. In order to better understand the interaction between these two domains during the COVID-19 outbreak, we aim to provide an extensive mapping of consolidated literature on this subject. Such a review, in the context of the COVID-19 outbreak, will inform decision makers on issues concerning the optimization of NPIs in view of the HED and its related tradeoffs. The literature review was conducted systematically in a multi-step process . Englishn = 50) underwent categorization of main themes and messages. This helped to map the overall landscape of the literature as is referred to in the primary body of the text. It also unveiled the need for information-based intelligent decision-support-systems that combine health and economy considerations. The study did not collect any primary data, and no data was collected from human subjects directly by the authors. The papers that completed full review  . GourincThe key issues of mitigation thus for epidemiologists, as presented by Anderson et al. (2020) , are minTo mitigate the infection and death curve and to ensure a more manageable stream of those requiring care from the healthcare system, aggressive social distancing has been deemed a viable and necessary NPI strategy by many experts ,43,44,45Where aggressive policies of social distancing were implemented, strong results in reduction of the virus spread were seen such as in China, Taiwan and Singapore . HoweverSubstantial amounts of literature acknowledge the detrimental and vast impact of the outbreak on economic activities ,63,64,65To further the discussion on the appropriateness of social distancing, the literature extensively explores the impact of social distancing policies on various sectors of the economy. As the global and national virus spread emergencies were declared, restrictions of movement resulted in limitations to economic activity . It is wFurthermore, the dislocation of many industries is estimated to increase global unemployment. In a low scenario, with GDP dropping by around 2%, an increase of 5.3 million unemployed is predicted, and in a “high scenario”, with GDP growth reducing by 8%, global unemployment would increase by 24.7 million ,71. It iDespite this, in both developing and developed countries, while still investigating the complete extent of impact, the effect on the economy has been profound. It is painfully evident that the increasingly strict measures imposed by governments will leave a toll on macro and micro levels . The immNaturally, the discourse surrounding social distancing policies and the impacts on the economy and health are considered in reference to various approaches undertaken by many countries. While cultural and additional differences such as socioeconomic status, political climate, etc., must be taken into consideration when doing cross-country comparison, approaches fall on a spectrum between limited containment measures, to drastic lockdowns, with most countries found somewhere in between these extremes ,78,79,80Given the complexity of societies, the myriad of potential policy interventions and the nature of this multifaceted global threat, a more nuanced approach to the HED is necessary in order to achieve optimal and effective policies which reconcile public health and economic interests. When charting a path forward for grappling with the ongoing pandemic, an optimal approach involves dynamically managing the tradeoffs between health and economic costs simultaneously, rather than solely focusing on health priorities or economic ones . As GourSilva et al. (2020)  propose The COVID-19 virus must be defeated but not at the expense of the economy . VariousThe return to normalcy will only occur through a complex assortment of additional interventions and policies. Testing, tracing and mask wearing have limited directly negative economic impacts and have been shown to substantially reduce spread of infections . AdditioThough decision-making during the COVID-19 pandemic is no doubt complicated by the need to consider opposing or at times, even contradictory views regarding antagonistic decisions, this is crucial to achieve an effective management of the situation. For example, deciding whether or not to issue a lockdown, mandate vaccinations or instruct on levels of clinical care in overwhelmed medical institutions, may necessitate a relative preference of the health or the economic consequences and thus impact on the course that will be defined. The benefit of considering these varied views is derived from the following factors: (1) As COVID-19 presents not only a health crisis but also a social and economic one, any decision has to first assess the relative contribution or damage that will be caused to each of these domains; (2) Any decision will substantially affect the lives of all populations, thus priorities need to be defined to ensure a just distribution of the burden; and, (3) To obtain an affective compliance of the public to the measures instructed by the authorities, the different concerns must be considered and applied in the decision-making, to achieve understanding and consensus as wide as possible. Lessons learnt from the initial stages of the COVID-19 outbreak indicate the need for a more coordinated economic and public health response. While social distancing has been shown in theoretical and epidemiological literature to be effective as an NPI measure to mitigate the spread of COVID-19, the economic costs have been substantial. New insights combining epidemiological and economic data are emerging which provide new theoretical predictions that can be used to better understand the health/economy tradeoffs. Findings from this literature review aim to elucidate perspectives to assist policy implementation related to the management of the ongoing outbreak and impending outbreaks of similar nature. While focusing on a survey of empirical papers, the work towards this review unveiled the need for information-based decision-support systems which will combine pandemic spread modelling and control, with economic models. Currently, as apparent from reviews such as in Musulin et al. (2021)  and TsenFuture research inquiries should dedicate an examination to geographic specific COVID-19 impact and respective attitudes regarding the HED. Additional considerations that were not elucidated in the above literature on the HED are the potential increased healthcare expenditures due to lack of attention to non-COVID-19 pathologies as well as the economic costs of productive age loss. Future studies should continue to follow the discussion on the COVID-19 HED in order to deepen the global community’s understanding on various aspects of the subject.


Continuous monitoring of physical motion, which can be successfully achieved via a wireless flexible wearable electronic device, is essential for people to ensure the appropriate level of exercise. Currently, most of the flexible LC pressure sensors have low sensitivity because of the high Young’s modulus of the dielectric properties (such as PDMS) and the inflexible polymer films (as the substrate of the sensors), which don’t have excellent stretchability to conform to arbitrarily curved and moving surfaces such as joints. In the LC sensing system, the metal rings, as the traditional readout device, are difficult to meet the needs of the portable readout device for the integrated and planar readout antenna. In order to improve the pressure sensitivity of the sensor, the Ecoflex microcolumn used as the dielectric of the capacitive pressure sensor was prepared by using a metal mold copying method. The Ecoflex elastomer substrates enhanced the levels of conformability, which offered improved capabilities to establish intimate contact with the curved and moving surfaces of the skin. The pressure was applied to the sensor by weights, and the resonance frequency curves of the sensor under different pressures were obtained by the readout device connected to the vector network analyzer. The experimental results show that resonant frequency decreases linearly with the increase of applied pressure in a range of 0–23,760 Pa with a high sensitivity of −2.2 MHz/KPa. We designed a coplanar waveguide-fed monopole antenna used to read the information of the LC sensor, which has the potential to be integrated with RF signal processing circuits as a portable readout device and a higher vertical readout distance (up to 4 cm) than the copper ring. The flexible LC pressure sensor can be attached to the skin conformally and is sensitive to limb bending and facial muscle movements. Therefore, it has the potential to be integrated as a body sensor network that can be used to monitor physical motion. As life expectancy and various health risks are simultaneously on the rise, people usually do physical exercises to maintain a healthy body. In order to reduce the risk of exercise injury, it is essential to continuously monitor limb motion magnitude for human health. Traditional rigid biomedical sensors have mechanical properties which are significantly different from those of the soft and curved surfaces of human tissues . FlexiblIn recent years, flexible wireless passive LC pressure sensors have been a hot research field. They provided a convenient solution that did not require power supplies or rigid chips, thereby making it well suited for wearable devices. Usually, the planar inductance is not only the basic unit that constitutes the LC electric resonant circuit but also acts as the antenna that achieves the transmission function of energy and data with the readout system. Furthermore, the capacitance acts like a pressure-sensitive unit that changes in response to different external pressures. Therefore, flexible LC pressure sensors have two advantages: small size and long lifetime, which makes the LC sensor superior in some applications such as implantable sensors and wearable devices .Previously reported flexible LC pressure sensors offered capabilities for the measurement of physical signals inside and outside the human body. Some LC sensors were fabricated by lithography, etching processes, or screen printing on the polyimide substrate. Bao et al. presented an ultra-small passive sensor whose pressure sensitivity was −1.428 MHz/mmHg for health monitoring and critical care . The seng method . The PDMg method . The capLC sensor can be prepared on a PET substrate through the electroplating process. Huang et al. proposed a symmetric LC circuit configuration for passive wireless multifunctional sensors. The sensor circuits on the top and bottom surface of the PET substrate were fabricated through an electroplating process, and the PDMS-based pressure-sensitive membrane with arrays of the inverted micro-pyramid was fabricated using a silicon mold. The sensitivity of the pressure sensor was −48.5 kHz/mmHg .Solution-free vacuum deposition of metals on a PDMS substrate is also a method of preparing LC sensors. Park et al. fabricated a wireless pressure-sensing platform used for parallel signal processing. The metal-based (Al or Au) 2D inductance coil was patterned in a solution-free manner using vacuum deposition, and the lateral electrode, made up of either Al or Ag nanowires, were patterned on the glass or PDMS. The pressure-sensitive element was a PDMS substrate with a pyramid structure .In addition, many groups have contributed to the advancement of implantable flexible LC pressure sensors for the measurement of internal physiological signals of the human body over the past decade.Piezo inkjet is an effective method for preparing LC inductor coils on a paper substrate. Tse Nga Ng et al. proposed a wireless pressure sensor with a pressure sensitivity of 0.011 MHz/mmHg prepared by inkjet printing to capture the heart pulse waveform. The inductor coil and the capacitor electrodes were patterned using a piezoelectric inkjet to print nanoparticle silver ink on a paper substrate. The porous dielectric layer was fabricated through polymethyl methacrylate microspheres mixed with PDMS and hexane in the specific ratio by weight. A piece of the Ag electrode with PDMS porous dielectric was bonded to the paper substrate with the complementary capacitor electrode and the inductor coil by using a diluted PDMS solution as the glue .Some people used the method of laser cutting metal layers to fabricate LC coils and electrodes. Rogers et al. presented a bioabsorbable wireless pressure sensor with pressure sensitivity of 200 kHz/mmHg for real-time monitoring of human internal pressure . Laser cElectron beam evaporation of metal particles was also commonly used in the preparation of LC coil antennas. Aleksi Palmroth et al. proposed a wireless bioabsorbable pressure sensor embedded in orthopedic implants with a pressure sensitivity of −6 kHz/mmHg used to monitor the healing process and detect complications. Conductor patterns were fabricated by the electron-beam evaporating the magnesium pellets onto the poly (DTE carbonate) substrate through 3D printed masks, and the compression-molded poly (DTE carbonate) spacer was used between two substrates to form a sandwich structure .In the above-mentioned work, most flexible LC pressure sensors were prepared on flexible polymer films such as PI or paper. Most flexible polymer films don’t have excellent stretchability due to their high Young’s modulus, which makes it difficult for them to conformally attach to arbitrarily curved and moving surfaces (such as joints) to continuously monitor bending. On the other hand, it is difficult to compress the dielectrics of most sensors such as PDMS because of their high Young’s modulus, resulting in the low-pressure sensitivity of the sensor. In addition, the above-mentioned work relied on the metal coil connected to the vector network analyzer to read the information of the LC sensor. Because the VNA is bulky and inconvenient to move, it is greatly restricted in daily applications.In order to solve the above-mentioned problems, we fabricated a flexible LC pressure sensor with Ecoflex  as the substrate that can be conformally attached to the arbitrarily curved and moving surface of the skin to monitor bending long-term. At the same time, we used a method of metal mold replication to prepare Ecoflex microcolumns as the dielectric of the pressure sensor. Because the gap in the dielectric constant value between Ecoflex material and PDMS material is small, and the Young’s modulus of the Ecoflex polymer is smaller than that PDMS polymer, the LC pressure sensor with Ecoflex microcolumns as the dielectric has higher pressure sensitivity than most of the previously reported work. The antenna can be utilized to transmit energy and information, and it has been widely utilized in RFID technology as one of the main components of the portable readout device. Here, we designed a coplanar waveguide-fed monopole antenna used to read the information of the LC sensor, whose bandwidth below −10 dB is wide enough to cover the probable range of frequency variation of the sensor.In this paper, we proposed a flexible LC pressure sensor with high-pressure sensitivity for the measurement of the physical activity signals. Firstly, the finite element analysis method helped to design and optimize the flexible LC pressure sensor to obtain high sensitivity. Secondly, inspired by the traditional Chinese dough figurines, the embossing method was proposed to prepare the required LC coil. At the same time, we used a simple metal mold replication method to prepare the dielectric of the LC pressure sensor. In order to obtain high-pressure sensitivity, we choose Ecoflex material with a lower Young’s modulus to replace the commonly used PDMS material. We proposed a transfer-paste method to prepare the flexible LC pressure sensors with a sandwich structure based on different flexible substrates, which can meet the needs of a variety of different bonding surfaces, and they can be integrated as flexible LC sensing arrays to solve the problem of complex wired sensor arrays. Thirdly, in order to be easily integrated with the radio frequency signal processing circuit to meet the development direction of the miniaturization and integration of the LC reader system, we designed a coplanar waveguide-fed monopole antenna used to read the information of the LC sensor, expanding the types of readout devices of sensors, and improving the vertical readout distance and horizontal readout range. Finally, to confirm the practicality of the fabricated pressure sensor, we used medical tape to stick it on different parts of the human body to measure physical activity, such as limb bending and facial muscle movement.The pressure sensor with high sensitivity in this paper can be used to monitor the distribution of pressures, bending of physical joints, and swelling in the injured area. The planar monopole antenna can be integrated with RF signal processing circuits as a miniaturized portable readout device. The whole-body wireless pressure sensing network will be constructed by sticking the pressure sensor to various parts of the human body and integrating the readout device on the clothes, which has great application potential in the monitoring and analysis of athletes’ physical motion signals and medical care.In this work, we introduced a flexible wireless passive LC pressure sensor that was attached to different body sites for the measurement of human body motions, as illustrated in  minimum . By analThe flexible LC pressure sensor is created by stacking a micro-column dielectric between the two capacitor plates in a sandwich structure , as depiTo evaluate the sensitivity and optimize the design of the flexible LC pressure sensor, the finite element simulation of the sensor under different pressures was carried out with the COMSOL software . In order to verify the frequency sweep range in simulation, theoretical formulas were utilized to calculate the inductance and capacitance of the LC pressure sensor to obtain its resonance frequency. The size parameters of the coil antenna and the micro-column dielectric are shown in For square planar inductors, the approximate formula of the current sheet derived from the basic electromagnetic theory is as follows :(1)L=[u0As shown in la below :(2)Ceff=L and C are the inductance and capacitance of the sensor tank, respectively. When the above-calculated values of inductance and capacitance are brought into the calculation expression of the resonant frequency, the calculated resonance frequency of the sensor is approximately 455 MHz.The resonance frequency of the flexible LC pressure sensor can be expressed as :(3)fS=12The sensitivity of the flexible LC pressure sensor was studied with the finite element simulation using the Electromagnetic Waves module and Solid Mechanics module of the COMSOL software. The Solid Mechanics module was taken advantage of simulating the compression of the sensor caused by external pressure, and the Electromagnetic Waves module was used to simulate the response of the readout antenna in the readout system. The meshed model diagram of the readout system of the sensor in the finite element simulation is shown in We used a finite element analysis to optimize the size parameters of the coil antenna and microcolumn dielectric of the LC sensor. As shown in The materials of the substrate, inductor coil, and micro-column were respectively set as polyimide (PI), copper, and polydimethylsiloxane (PDMS), as illustrated in The stress distribution of the sensor with an Ecoflex micro-column as the dielectric, under an applied pressure of 2000 Pa over the surface, is shown in A method of metal template replication was used to prepare the Ecoflex micro-column dielectric, which was cheaper than the preparation process of the microstructure dielectric and simpler than the fabrication method of the composite dielectric; the manufacturing process is shown in Inspired by the embossing technology of the Chinese traditional dough sculpture process, we proposed an embossing process to prepare the LC coil antenna, which was simple and low-cost compared to the reported works. In this paper, we presented a transfer-paste method for the fabrication of the flexible LC pressure sensor, which can achieve sensors based on various dielectrics and substrates. It provided a new idea for the preparation of LC sensors. The manufacturing process of the sensor is depicted in To wirelessly interrogate the flexible LC pressure sensor, a readout copper ring  connected to the vector network analyzer was near-field electromagnetic coupled with the sensor, as shown in The impedance of the readout copper ring (essed as :(4)ZR=RRThe impedances of the flexible LC pressure sensor (The impedance of the sensor is :(5)ZS=RSk) and the quality factor (Q) of the sensor can be expressed as [M is the mutual inductance between the readout coil and the pressure sensor.The coupling coefficient (essed as :(6)k=MLRBy using the Equations (4)–(7) the impedance of the readout coil can be further expressed as :(8)ZR=RRFor a one-port measurement system, the input return loss, essed as :(9)S11=ZAccording to Equations (8) and (9), the measurement depends critically on the coupling coefficient between the pressure sensor and the readout copper ring. Therefore, the relative position between them is important .To examine the influence of different vertical readout distances, the readout copper ring was placed underneath the LC pressure sensor, and the sensor was placed on the acrylic tables with different heights. Changes in the resonant frequency of the sensor are shown in The effect of different horizontal displacements is shown in The rotation of the readout copper ring was adjusted using acrylic tables with different angles. These measurements demonstrate a robust reading range of vertical distances of 0–2.5 cm, horizontal displacements of 0–1.5 cm, and rotation angles of 0–In order to test the sensitivity of flexible LC pressure sensors, the metal weights with different masses were used to apply pressures to the sensors, and a small plastic dish was placed between the metal weight and the sensor to avoid producing additional parasitic capacitance, as depicted in The resonance frequency of the flexible LC pressure sensor based on Ecoflex substrate and micropillar dielectric is 360.6 MHz in the case of only the small plastic dish applied. With the applied pressure increasing, its resonance frequency decreases linearly, reaching 311 MHz under the pressure of 23,760 Pa. The LC pressure sensor has the PI substrate and Ecoflex microcolumn dielectric, whose resonant frequency reduces from 384 MHz to 323 MHz when the pressure increases from 675 Pa to 23,760 Pa. For the LC pressure sensor of the PDMS substrate and dielectric, its resonant frequency decreases linearly from 385 MHz at a pressure of 675 Pa to 368 MHz at a pressure of 23,760 Pa.Due to the different dielectric constants existing in various flexible substrates, the initial values of the resonance frequency among the sensors are different. Meanwhile, considering the effect of the dielectric properties of the small plastic dish on the sensor, the initial resonance frequency of the LC sensor is placed in the presence of the small plastic dish to only represent the effect of different pressures on the resonance frequency of the sensor.The flexible LC pressure sensor designed based on Ecoflex material in this paper not only has higher pressure sensitivity than most sensors reported in the existing works  is 8 cm, calculated from Formula (11).The formula of the distance of the antenna’s inductive near-field zone isAs shown in From B is magnetic induction, r is the distance from the current element to the point, and Compared to the copper ring, the monopole antenna can read the information of the LC sensor reaching a distance of 4 cm. The reason is that the magnetic induction generated by the planar monopole antenna is higher than the copper ring. According to Biot-Savart law, the strength of the magnetic induction at a certain point is equal to the sum of the magnetic induction strength of each current element, expressed asTo examine the influence of horizontal displacement, the monopole antenna was placed underneath the sensor at a fixed distance of 1 mm, and the measured resonance frequency curves were depicted in It is demonstrated in research , the monThere is a robust range of the vertical distance from 0 to 4 cm, the horizontal displacement from 0 to 8 cm, and the rotation angle from 0 to In order to further verify that the monopole antenna can accurately read the information of the LC sensor, it was used to measure the sensitivity of the pressure sensor, as shown in By comparing the information of the sensors read by two readout devices, the measured results of using a planar monopole antenna as the readout device basically agree with the test results of the copper ring, which further verifies the feasibility of the application of the monopole antenna in the readout system of the wireless passive LC sensor. The feasibility of the coplanar waveguide fed monopole antenna as a reader antenna has been verified in GHz frequency band applications . In thisWith life expectancy and various health risks rising simultaneously, flexible wireless wearable electronic devices have been studied extensively and used for continuous health monitoring and instant diagnoses to improve people’s health . CurrentThe sensor was attached to a finger to measure the finger bending movements , as illuThis work suggests that the planar monopole antenna acting as a reader antenna of the LC sensor can be used to monitor human activity signals, although it is influenced by the dielectric properties of the human skin to a certain extent. This also provides an optional readout antenna for a miniaturized, integrated mobile terminal readout device in an LC sensing system, which may be used in medical monitoring systems.To further investigate the performance of the sensor in terms of human movement monitoring, we attached the sensor to the face (center of the forehead) to monitor the facial muscle movements of a smile or frown, as depicted in People inevitably have bumps during exercise and daily life, resulting in swelling of the skin. The degree of swelling of the skin should be monitored at all times to help with time-consuming and effective treatments of the swollen area. We used the medical tape to stick the flexible LC pressure sensor on the surface of the balloon and use the balloon’s expansion to simulate the swelling of the skin, as illustrated in Therefore, the sensor can wirelessly detect limb bending and facial muscle movements, which gives it the potential to construct a body wireless sensor network for motion monitoring and pressure mapping.In summary, we proposed a sandwich-structured flexible LC pressure sensor based on an Ecoflex micro-column as a dielectric, which is sandwiched between the two capacitor plates of the coil antenna. To guide the design and optimization of the sensor, a finite element simulation is used to evaluate the performance of the sensor. We presented a simple embossing process to emboss copper conductive tape to prepare a low-cost coil antenna and a transfer-paste method to fabricate the pressure sensor. The resonance frequency of the sensor changes as a linear function of applied pressure in a range of 0–23,760 Pa with a sensitivity of −2.2 MHz/kPa that is higher than most of the sensors reported in the existing works. We further demonstrated its potential to be integrated into a pressure sensing array with excellent performance. In addition, we also designed a planar monopole antenna to expand the types of readout devices and increase readout distance. The flexible LC pressure sensor can be used to measure various physical activity signals for continuous health monitoring. Looking to the future, the sensor can be combined with an external readout circuit to construct a portable wireless real-time monitoring system. Furthermore, when combined with various chemical materials and biomedical technologies, the LC sensor can be constructed as a multifunctional sensing device, with potentially essential applications in continuous wireless monitoring of multiple physiological parameters for biomedical research and patient care.


Microfluidic biochips have been in the scientific spotlight for over two decades, and although technologically advanced, they still struggle to deliver on the promise for ubiquitous miniaturization and automation for the biomedical sector. One of the most significant challenges hindering the technology transfer is the lack of standardization and the resulting absence of a common infrastructure. Moreover, microfluidics is an interdisciplinary field, but research is often carried out in a cross-disciplinary manner, focused on technology and component level development rather than on a complete future-proof system. This paper aims to raise awareness and facilitate the next evolutionary step for microfluidic biochips: to establish a holistic application-agnostic common microfluidic architecture that allows for gracefully handling changing functional and operational requirements. Allowing a microfluidic biochip to become an integrated part of a highly reconfigurable cyber-fluidic system that adopts the programming and operation model of modern computing will bring unmatched degrees of programmability and design reusability into the microfluidics field. We propose a three-tier architecture consisting of fluidic, instrumentation, and virtual systems that allows separation of concerns and promotes modularity. We also present BiowareCFP as a platform-based implementation of the outlined concepts. The proposed cyber-fluidic architecture and the BiowareCFP facilitate the integration between the virtual and the fluidic domains and pave the way for seamless integration between the cyber-fluidic and biological systems. The miniaturization and integration in the microelectronics industry have been exponentially growing since the introduction of the first commercially available microprocessors in the early 1970s. The commercial debut of the microprocessor marked the beginning of a new era, where computers became compact and economically feasible for use in everyday life. Fast forward 50 years, and we see a ubiquitous mixture of personal computers, portable devices, and various cyber-physical systems connecting our tangible world with the emerging virtual world.In a similar manner, the miniaturization and integration of the traditional wet laboratory processes started gaining traction in the early 1990s when the first ideas about miniaturized total chemical analysis systems (µTAS) were introduced [The vision for microfluidic biochips overtaking the field of medical and biological analysis has been described as the motivation for countless research papers. Lower reagent volumes, automation potential, shorter hands-on time, miniaturization, scalability, and reduced overall costs are often articulated as key selling of the microfluidic technology. However, despite the strong technological development and great potential, 30 years later, the microfluidic biochips still mostly remain in the academic domain, where scientists focus on technological advancements and writing scientific papers about them .The field of microelectronics was first driven forward by engineering and academic interest, but it was profoundly supported by the revenue generated from the steadily increasing market demanding higher-performance computers. Likewise, finding a commercially viable “killer application” that will fuel the technological transfer and overcome the remaining technological challenges is, in theory, the key to pushing microfluidic biochips past the proof-of-concept stage.Some of the most exciting microfluidic applications relate to the healthcare sector or the emerging biological computing and synthetic biology fields. Unfortunately, the research record shows that seeking a commercial “killer application”  often appears in the context of short-term research goals. This strategy inherently lacks the means to facilitate sustainable technological development; i.e., it produces proof-of-concept prototypes that have limited applicability to a small subset of problems. Without a common infrastructure, a significant portion of each research endeavor often goes into trivial but cumbersome microfluidic engineering, establishing fabrication processes, and building instrumentation systems, instead of focusing on what is important, i.e., bringing value and solving real problems.In contrast, the microelectronics and computer industries heavily rely on standardization and design reuse, where a new system is often primarily made of already existing modules. It is seldom the case that a computer is built from scratch or software is written without an external codebase and extensive toolchain. Modern computer systems can be reconfigured and reprogrammed, which allows focusing on what is essential—building applications and solving complex problems quicker, better, and at a reasonable cost.Nevertheless, one might ask why the parallels between the computer and microfluidic biochips are relevant. The intersection between the cyber and the physical domains is what we believe is immediately relevant to the microfluidic biochips, i.e., a programmable cyber-fluidic architecture that links the computational capabilities of the virtual world with the liquid and biological handling capacity of the microfluidic biochips. Allowing a microfluidic biochip to become an integrated part of a highly reconfigurable cyber-fluidic system that adopts the programming and operation model of modern computing holds the potential to disrupt the fields of life and computer science. Undoublty, the underlying biological mechanisms are far more involved than the computer system, but the fluidic handling in its essence is not much different from operations performed with virtual data.The rest of this paper focuses on what we believe is the missing link for establishing a common microfluidic infrastructure—a cyber-fluidic architecture that has the potential to mark the next evolutional step of the microfluidics development. We argue about the advantages and demonstrate the feasibility of the suggested architecture by unfolding the concepts into a modular cyber-fluidic platform instance called BiowareCFP. The platform prototype is shown in There are two dominant active microfluidic handling technologies: channel-based continuous flow and planar digital microfluidics, as shown in In contrast, digital microfluidics allows the manipulation of individual droplets on a planar surface. Droplet actuation is achieved by an electrical field, thereby allowing for a relatively simple first-order digital-to-fluidic interface. Handling discrete volumes provides a straightforward method for controlling chemical species’ concentrations, and it closely resembles the operations typically performed as a part of a benchtop laboratory protocol. The lack of physically defined channels and potentially bulky external instrumentation favors programmability and moderate the scalability challenges.The two technologies have their strengths and weaknesses. Although we do not advocate that digital microfluidics is technologically or functionally superior, we believe that digital microfluidics, with its simple construction and elegant operation principle, appears to be better suited for creating a universal programmable cyber-fluidic processor capable of handling various chemical species. While the strategies for creating a universal cyber-fluidic system certainly extend beyond the boundaries of the two mentioned microfluidic technologies, we chose digital microfluidics as the rational point of departure.Digital microfluidics (DMF) operates on a planar array of individually addressable electrodes coated with a hydrophobic isolation layer. Droplet actuation is achieved by controlling the surface wettability as a function of an electric potential applied to pairs of adjacent electrodes. This technique is known as electrowetting on dielectric (EWOD) , and it Digital biochips exist in open or closed configurations, as shown in A digital biochip’s functionality can be further enhanced with electrochemical ,10,11 anAlthough the EWOD appears to be a straightforward droplet actuation method, employing it for digital biochips poses a wide range of technological challenges. Device properties such as substrate material, fabrication methods, electrode geometry, coating material, and gap height must be carefully chosen to achieve reliable and repeatable droplet actuation . MoreoveDespite two decades of digital microfluidics development , a largeDesigning and building a full-stack cyber-fluidic system is beyond the scope of a single technological domain. A multidisciplinary effort where different disciplines work closely together is considered a minimum requirement. However, full-stack cyber-fluidic development greatly benefits from an interdisciplinary approach where knowledge and methods from the different technological domains are blended to solve the challenge at hand. Although one can argue that this reasoning seems obvious, it raises the question of why the field of cyber-fluidic systems yet remains somehow immature. There is a lack of standardization on all levels. A common digital biochip form factor is virtually non-existent, and electrode layout is often done in graphical editing software, besides the existence of attempts for layout automation ,23. AparNevertheless, several instrumentation systems have emerged as cornerstones on the path towards programmable cyber-fluidic systems. The most notable example is the open-source DropBot system , which aRecognizing the lack of standardization and reflecting on the interdisciplinary paradigm—i.e., the knowledge and methods from the different technological domains are combined to solve problems—allows for drawing parallels between the digital microfluidics domain and the heavily standardized and automated field of computer science and microelectronics ,32. We aA platform-based modular design approach ,33 allowThe fluidic system is responsible for the liquid sample handling, and it includes a digital biochip and any associated auxiliary sensors and actuators. The fluidic system is the most delicate and technologically challenging of the three platform parts, and therefore, the modularity and functional mapping of the instrumentation and the virtual systems are governed by the features and limitations of the fluidic system.The instrumentation system is the link between the cyber and fluidic components of the platform see , and it A full-stack software toolchain, including manual and automated instrumentation system control, high-level protocol capture, translation, and execution on the digital biochip, can be built on top of the cyber-fluidic platform. The software stack represents the virtual system see , and itsThe modular design approach promotes encapsulation and allows agile development of different functionalities. The platform modules interconnect through defined interfaces on the physical, electrical, and protocol levels. Examples of such interfaces are the control, feedback, and supply communication buses shown in The modular design and the one-to-one functionality mapping in the instrumentation system allow for creating an application-specific platform instance from a library of building blocks. This process is illustrated in The EWOD droplet actuation relies on the properties and quality of the digital biochip electrode array the hydrophobic insulation layer. This splits the fabrication of the digital biochips into four parts: (i) fabricating the electrode patterned substrate, addressed in Glass and silicone substrates with electrode patterns created by photolithographic processes are de facto the standard fabrication method for digital biochips. Another alternative includes printing on low-cost substrates, such as paper  or plastFast prototyping printed circuit board (PCB) services have emerged in recent years, and the current fabrication capabilities readily allow for low-cost multilayer PCBs with 100 The typical coating approach for digital biochips is a two-step process that consists of the deposition of an isolation layer followed by a fluoropolymer coating. The first layer provides electrical isolation, and the hydrophobic coating ensures low surface energy and a high contact angle. Creating these two layers is a time-consuming, multistep process that requires specialized equipment. However, manipulating reagents with high protein content inevitably leads to surface contamination known as biofouling. This unwanted deposition of proteins or other biomolecules affects the droplet transport and poses the risk of sample cross-contamination to an analyte that passes through the fouled area. Although methods for mitigating biofouling, such as using filler fluids or additives, exist , biofoulAn alternative single-step foil coating method has been demonstrated to be a feasible and inexpensive approach ,27,36. FThe foil-based approach fits the modularity paradigm, and it provides another reconfigurable layer to the fluidic system. Different foil materials, surface treatments, and foil frame holders can be used to adapt the digital biochip to the experimental needs.A closed digital biochip top plate is usually made of indium tin oxide (ITO)-coated glass or ITO-coated polyethylene terephthalate (PET), as illustrated in The variety of available sensors and actuators were mentioned in The instrumentation part of the cyber-fluidic architecture consists of a set of connected embedded systems. They are grouped by functionality into a modular instrumentation subsystem and a base control system, as shown in The control, feedback, and supply modules form the instrumentation subsystem, and each module is designed to address a specific digital biochip instrumentation need. For example, the minimal digital biochip instrumentation system consists of the base control system , an electrode driver module, and a high-voltage power supply module. The high-voltage power supply is connected to the supply bus, and it provides the required actuation voltage to the electrode driver module responsible for driving the digital biochip electrodes.The instrumentation subsystem is assembled as a subset of a collection of existing application-specific modules, as previously illustrated in Virtual and physical modularity is essential for compatibility and future interoperability. Moreover, defined interfaces on the software and hardware levels are a necessity for the plug-and-play functionality. A module form factor governed by multiples of 1U  instrumentation prototype was earlier shown in The fluidic system is based on a PCB digital biochip, and its design is shown in The multilayer PCB structure also allows for fabricating embedded meander structures between adjacent columns of electrodes, as shown in A foil-based approach was adopted for coating the electrode array. A sub- 10 The instrumentation system was composed of a collection of hardware modules to verify the cyber-fluidic architecture design concepts and assumptions. Eight hardware modules were developed in total; the first seven were initially intended, and the additional eighth module was developed as a result of the expansion of the application space requirements see . The iniThe mainboard is the brain of the instrumentation system, and it contains various subsystems, such as communication, computation, and storage subsystems; a user interface; and interfaces for connecting external devices. The mainboard connects to the instrumentation bus interface, graphical display, user interface controls, external storage memory card, and power delivery system. The design is focused on striking a balance between being a capable, compact, and feature-rich but power-efficient embedded system that fits into the 4 U/4 U form factor.The bus interface links the mainboard with the instrumentation modules. It implements the physical layer of the supply, control, and feedback buses and provide power to the attached modules. The three buses are electrically decoupled from each other by the use of digital isolators and separate power supply domains. The complete electrical isolation mitigates eventual cross-system disturbance and favors a fault-tolerant operation.The power delivery module creates the multiple power domains required by the mainboard, the bus interface, and the instrumentation subsystem, and it is designed to fit the 4 U/4 U form factor. For the sake of portability, the module is designed to operate from a rechargeable battery pack, including charging and protection circuitry. The battery pack capacity can be adjusted to match the power needs of a given platform instance.Digital microfluidics requires electrode control voltages in the range of tens to hundreds of volts, depending on the dielectric properties of the coating layer . A typic 5–10 μm . ActuatiThe electrode driver module is implemented as an array of individually addressable high voltage switches providing a one-to-one mapping of driving channels to the digital biochip electrodes. This mapping scheme is the most flexible programming approach, since each control electrode has a dedicated driving channel. The electrode driver module was designed in 4 U/4 U form factor, and it has 384 driving channels that can be updated every 50 The heaters controller module can instrument up to three temperature regions, where each region is created from an arbitrary number of adjacent heaters connected in series. Each temperature region is controlled by a proportional–integral–derivative (PID) controller, allowing the setpoint and the thermal response of each temperature zone to be software controlled.A generic microcontroller module and a carrier board were designed to aid the development and prototyping of the instrumentation modules. The microcontroller module was used as a base for every instrumentation module, embracing design reusability on hardware and software levels.The platform-based design allows system development to be carried out simultaneously from top-down and bottom-up system perspectives. The proposed cyber-fluidic architecture holds the potential to combine the high-level synthesis tools  with theentation . Indeed,fISA see  is underUnderstanding and addressing the intrinsic relationships spanning across the system’s domains is essential for overall cyber-fluidic architecture. Nevertheless, foreseeing all possible benefits and shortcomings of a given approach in the context of a full system is virtually impossible, especially considering the constant technological developments. To deal with the complexity and uncertainty, we devised a modular platform-based cyber-fluidic architecture. The separation of the fluidic, instrumentation, and control concerns, plus the modularization within each system, create an evolvable platform framework that can be modified and expanded to meet virtually any emerging need.The baseline functionality of BiowareCFP was tested by performing single and parallel droplet manipulations in an open and closed digital biochip see . While tThe temperature sensor array and a corresponding instrumentation module were developed to assist with profiling and calibrating the temperature response of the digital biochip. The module allowed for real-time capturing of 40 temperature points distributed over the electrode array. The captured data were used for fine-tuning the thermal performance of the heating zones in a realistic operational environment. A heatmap sequence visualization of the generated three temperature zones in a closed digital biochip is shown in The development and straightforward integration of the temperature sensor array and instrumentation module with the rest of the BiowareCFP serves as a clear example of the advantages of the modular platform-based approach. The modularity of the fluidic system, e.g., the removable top plate, allowed the temperature sensor array to be installed between the digital biochip and the top plate, and the removable foil frame could be replaced after calibrating the temperature response of the system. The modular instrumentation subsystem provided a standard interface to the rest of the BiowareCFP. Moreover, the addition of the heaters controller and the temperature sensor array and interface modules can be used as practical examples of the extensibility and reconfigurability of the proposed cyber-fluidic architecture. This can be seen in Preliminary results from the implementation and testing of the envisioned There are still various engineering challenges to be addressed, such as integrating biosensors and designing the corresponding instrumentation modules. However, based on the developed framework and the high degree of modularity, we argue that the BiowareCFP provides an application-agnostic approach for developing cyber-fluidic system. Preliminary results on performing space domain PCR as a part of cell cloning and magnetic beads-based ELISA can be found in . The resIn addition to the technological challenges, substantial performance, programmability, reliability, and socioeconomic roadblocks need to be overcome before the cyber-fluidic systems realize their full potential as capable fluidic handling technology. We argue about the importance of standardization, unification, and reusability, which should significantly accelerate the technology transfer process. Moreover, we advocate for a strong interdisciplinary approach to digital microfluidics in order to raise awareness and emphasize the need for a holistic approach that has the merits to establish the envisioned universal microfluidic framework.We introduced the term cyber-fluidic systems and established the groundwork for implementing the envisioned framework based on digital microfluidics. Although we realize that the proposed architecture might not be the panacea for solving all microfluidics challenges and likely has limitations, it is a step towards more capable and integrated cyber-fluidic systems. We consider the implementation of the BiowareCFP to blur the boundaries between the software and fluidic domains and start the shift towards Bioware systems—a concept signifying the seamless integration between the cyber-fluidic system and biology. A particularly relevant class of applications comes from the synthetic biology field, where the BiowareCFP provides the means to create or modify biological parts, reprogram living cells, and to be used for biological computing. It has been an exciting couple of decades for the microfluidics field, and we believe the highly anticipated “killer application(s)” and consequent commercialization are on their way.


As vaccination campaigns are in progress in most countries, hopes to win back more normality are rising. However, the exact path from a pandemic to an endemic virus remains uncertain. While in the pre-vaccination phase many critical indoor situations were avoided by strict control measures, for the transition phase a certain mitigation of the effect of indoor situations seems advisable. To better understand the mechanisms of indoor airborne transmissions, we present a new time-discrete model to calculate the level of exposure towards infectious SARS-CoV-2 aerosol and carry out a sensitivity analysis for the level of SARS-CoV-2 aerosol exposure in indoor settings. Time limitations and the use of any kind of masks were found to be strong mitigation measures, while how far the effort for a strict use of professional face pieces instead of simple masks can be justified by the additional reduction of the exposure dose remains unclear. Very good ventilation of indoor spaces is mandatory. The definition of sufficient ventilation in regard to airborne SARS-CoV-2 transmission follows other rules than the standards in ventilation design. This means that especially smaller rooms most likely require a significantly greater fresh air supply than usual. Further research on 50% group models in schools is suggested. The benefits of a model in which the students come to school every day, but for a limited time, should be investigated. In terms of window ventilation, it has been found that many short opening periods are not only thermally beneficial, they also reduce the exposure dose. The fresh air supply is driven by the temperature gradient and wind speed. However, the sensitivity towards these parameters is not very high and in times of low wind and temperature gradients, there are no arguments against keep windows open in order to make up for the reduced air flow rate. Long total opening periods and large window surfaces will strongly reduce the exposure. Additionally, the results underline the expectable fact that exposure doses will increase when hygiene and control measures are reduced. It seems advisable to investigate what this means for the infection rate and the fatality of infections in populations with partial immunity. Very basic considerations suggest that the value of aerosol reduction measures may be reduced with very infectious variants such as delta. Airborne transmission has been found to play a major role in the spread of SARS-CoV-2. Although health authorities such as the CDC claim that it is not subject to “true airborne infection”, the fact that accumulation of small infectious aerosol particles causes numerous infections in poorly ventilated indoor environments is no longer in doubt , [2], 33, 4], , 55, 6]. T. T6]. ThThe sensitivity of exposure towards SARS-CoV-2 aerosols in the presence of one infected person was investigated by modelling indoor situations. The model is described and all functional parameters were evaluated in order to meet the current state of research. In the first part of the simulations, a sensitivity analysis was carried out for general parameters of indoor environments, and in the second part specifically for window ventilation. The sensitivity analysis shows the relative change of the exposure compared to the change of fundamental environmental parameters, starting from a defined situation (zero situation). In order to assess the extent to which the results are affected by the specificity of the zero situation, the zero situation was shifted to the upper and lower limits of the first analysis. This was done for three parameter pairs.A discrete, transient unsteady time-step model was developed to describe the exposure dose in presence of one infected person. The model needs to be fed with input parameters defining the modelled situation, while pre-set functional parameters define the biological and technical setting. The parameters are processed in both static and dynamic equations, which are updated at every time or iteration step. The time steps are iteratively scaled down by a divisor until the difference of the exposure between the last two iterations falls short of the defined maximum value for the convergence. The general behavior of aerosol transport from person to person is close to the analytical function of a Wells-Riley model, but it allows the use of transient and discontinuous functions for the input parameters. The model can handle absolute doses , but for our calculations of sensitivity, relative doses were sufficient. Figure 1Dynamic model equationsFor dynamic model equations, see Figure 2 Static model equationsFor dynamic model equations, see Figure 3 Output valuesFor output values, see Table 1 (Tab. 1)Input parameterFor input parameters, see Table 2 (Tab. 2)Functional parameter (pre-set)For functional parameters, see Table 3 (Tab. 3)AC – activity factorThe activity factor for breathing, talking and singing refers to measured particle mean flows for certain activities as published in . The AC CADRleakage – leakage air flow of the building Every building has a natural air flow through leakages, providing additional fresh air. The values for this air flow are subject to high variations. While modern energy-optimized buildings have very low natural leakages, older buildings are not as air tight. For instance, Howard-Reed et al.  suggest CADRwin– fresh air supply through windows The fresh air supply through windows is estimated by a model which was experimentally verified in . The tem – ventilation efficiency Dilution ventilation, which typically has a ventilation efficiency of 1, is assumed for all three types of fresh air supply . There aMV – minute volume The amount of inhaled particles correlates to the air volume breathed in by an exposed person. Therefore, people with smaller lungs  inhale fewer aerosol particles, while activities like sports increase the exposure. On the other hand, smaller lungs emit less aerosol, while sports increase the amount due to the increased minute volume. The data for different ages are based on , the valPMaskThe penetration of the masks needs to be considered in both directions: It reduces the aerosol emission of the infected person and the exposure of the healthy persons. The theoretical efficiency of professional masks  is very high . However, in everyday use, the aging of the masks, tight wearing and discipline of the users reduce the efficacy. Besides the technical approach, epidemiological studies provide data for the real-life efficicacy of masks. Mitze et al.  suggest λ – decay rate of viable SARS-CoV-2 in aerosols 2O from the air . H. H2O fro the air . This stIn order to verify the decay function in the model, we applied it to a room with an initial SARS-CoV-2 concentration of 1, without a source function (no infected person at t=0). Figure 4 2 concentration is kept well under 1,000 ppm. The ventilation in many real classes may be much worse. The concentration trend is typical for a constant fresh air supply. After a buildup phase, which lasts about 30 minutes in this case, the concentration of SARS-CoV-2 reaches equilibrium. While the increase of the cumulated exposure SHRED(t) increases exponentially in the steep build-up phase, the increase becomes linear during the equilibrium state. For the general analysis, the relevant input values for the zero situation (starting point) are shown in Table 4 The results of the sensitivity analysis are shown in Figure 6 An increase of mask efficacy causes a log-decay of the exposure. This means that wearing a mask at all, even with low efficacy, is very effective in reducing the exposure dose, while the curve flattens for higher efficacy. In spite of the fact that the theoretical technical potential of professional masks is >90%, the average real-life performance is likely to be significantly lower, as already discussed in the parameter evaluation. Therefore, the reduction values for 90% efficacy may only be possible in very professional settings, if at all. Besides the problem that highly effective masks absolutely require continuous checking of their tightness of fit in order to achieve their whole filtration potential, factors such as beards and differing facial forms facilitate leakages. Additionally, it must be considered that most professional masks are made of synthetic materials, which depend on their electric charge and their microstructure in order to achieve their specified efficacy. The re-use and long-term use of the same mask are likely to significantly reduce its efficacy. Therefore, rules demanding the strict use of professional masks should be critically questioned, since other factors such as costs and additional waste also need to be taken into account.To gain better understanding on how much the sensitivity behavior is related to the specificity of the zero-situation, we tested how the sensitivities affect each other by shifting the zero situations to the maximum and minimum values of the parameter change for parameter pairs. The max. and min. values thus become the new zero points and the parameter and exposure change is shown relative to them . This means that for the lines not intersecting 0.0, the parameter changes need to be calculated by subtracting the  values from the connecting knot to the lines passing 0.0. Figure 6 Figure 7 The most conspicuous curve in Figure 8 For the sensitivity analysis of window ventilation, a slightly different zero situation “Zero 2” was defined. Table 6 Only the extension of the total opening duration has a similar effect on the exposure. It reduces the exposure with increasing duration almost in parallel to the increasing window surface. For durations longer than in the Zero 2 situation, the curve slowly starts to show an even stronger decrease of exposure. In any case, we have to keep in mind that, as already explained in the model description, the CADR may be slightly overestimated for long opening periods and large temperature differences. The other conspicuous curve is the one for the intervals. The number describes how many different sections into which the total opening time is divided. These intervals are always centered on the time line. The same closing times are used before the first, after the last and in-between all openings. This is the only discrete parameter in this analysis. During the closing intervals, the aerosol concentration is only reduced by the decay of the viability and the very low leakage air flow, which leads to a strong build-up of the concentration in the presence of an infected person. Since the exposure is an integral function of the concentration, the unventilated periods should not be too long, in order to avoid high concentration levels, which contribute strongly to the exposure.Therefore, the exposure decreases with increasing number of intervals. The decrease is very strong when the amount is increased from one opening to three and becomes a little weaker for further increases. This is because with an increasing number of intervals, the opening time per interval decreases and the reduction of the concentration will stop at relatively high levels. From the thermal point of view, short opening is also preferable on cold days. Both wind and temperature differences are the physical forces which force the air to flow through the window. Figure 11 Summarizing the results of the basic parameter sensitivity analysis, it can be said that:Small rooms significantly increase the exposure. Good ventilation reduces the effect. For very short time periods, the use of (preferably ventilated) small rooms seems acceptable.Poor ventilation increases the exposure strongly, especially in small rooms. This is only acceptable for very short time periods.Exposure time has a very strong effect on the exposure. Doubling the exposure time will most likely more than double the exposure. Especially in poorly ventilated rooms, this happens at a high level of exposure. Reducing the time of event seems to be one of the strongest measures to reduce aerosol exposure.Masks are also a very strong mitigation measure. The effect is the strongest for the first ~50% of mask effectivity. Therefore the use of any kind of masks is highly recommended for indoor settings. Whether or not the obligation to wear professional high quality masks are worth the additional effort must be critically examinedThe reduction of control measures will obviously significantly increase the aerosol exposure dose in presence of an infected person Summarizing the results of the window ventilation parameter sensitivity analysis, it can be said that:total window surface and total opening time will increase the fresh air supply and greatly reduce exposure A sufficient number of intervals into which the total opening time is divided should not be too low. Long closing periods need to be avoided.The Temperature difference and wind are the driving forces of the fresh air supply. However, exposure is not extremely sensitive to them. In case that both are very small, and keeping the windows open may solve the problem sufficiently in many settings.window height affects the exposure, but the sensitivity is not high.The In order to assess the value of exposure reduction measures for specific situations for infection prevention and fatality reduction, further investigations are required. Looking at a quantum dose curve . The manuscript was written independently of this activity, without any company involvement.


Aircraft detection in remote sensing images (RSIs) has drawn widespread attention in recent years, which has been widely used in the military and civilian fields. While the complex background, variations of aircraft pose and size bring great difficulties to the effective detection. In this paper, we propose a novel aircraft target detection scheme based on small training samples. The scheme is coarse-to-fine, which consists of two main stages: region proposal and target identification. First, in the region proposal stage, a circular intensity filter, which is designed based on the characteristics of the aircraft target, can quickly locate the centers of multi-scale suspicious aircraft targets in the RSIs pyramid. Then the target regions can be extracted by adding bounding boxes. This step can get high-quality but few candidate regions. Second, in the stage of target identification, we proposed a novel rotation-invariant feature, which combines rotation-invariant histogram of oriented gradient and vector of locally aggregated descriptors (VLAD). The feature can characterize the aircraft target well by avoiding the impact of its rotation and can be effectively used to remove false alarms. Experiments are conducted on Remote Sensing Object Detection (RSOD) dataset to compare the proposed method with other advanced methods. The results show that the proposed method can quickly and accurately detect aircraft targets in RSIs and achieve a better performance. With the rapid development of image sensing technique  and aeroRecently, various methods have been developed for aircraft detection in RSIs. Those methods can be roughly divided into three categories: attribute-based methods, traditional learning methods, and deep learning methods . As for The traditional learning methods are mostly based on Viola-Jones (VJ) Object Detection Framework . These mDue to the increase in hardware computing ability and the easy access to big data, deep learning methods have achieved great success in natural images. Many studies have also introduced deep learning methods to RSIs analysis. For instance, Ding et al.  adopted With the increasing research on the deep network, some advanced relevant works are proposed in the field of remote sensing. For instance, graph convolutional networks (GCNs)  are suitThough there are many advantages, deep learning methods require too much labeled data and a long time to complete the training process. Moreover, the implementation of these algorithms requires the support of GPUs and parallel computing. For small platforms such as UAVs, the use of GPUs will increase the carrying burden, power consumption, and economic costs . TherefoTo solve the above problems, a new aircraft target detection scheme is proposed in this paper. The flowchart of the proposed method is shown in The remainder of this paper is organized as follows: In this section, we propose a fast convolution method based on circular intensity signal filter to obtain the center-response magnitude maps based on the structural characteristics of the aircraft targets. The threshold segmentation method is applied to operate on the response magnitude maps to get binary images containing the central regions of the aircraft. Then the center points of the target can be determined by clustering algorithm. Candidate regions can be generated by adding specific bounding boxes. In order to get the potential locations of the aircraft with different sizes, we build three-layers image pyramids for the original RSIs and operate on each layer of the pyramid.Due to the dynamics of atmospheric flight, the shape of most aircraft is fixed and can be simply broken down into a nose, a fuselage, a tail, and two wings according to the top view of the aircraft target. The aircraft structure is a cross structure, and the intersection of the fuselage and wings is the center of the aircraft.If taking the aircraft center as the center of a circle, choose a diameter greater than the width of the fuselage but less than the length of the wingspan to make a circumference. The grayscale value of the image is obtained counterclockwise with this circumference, and it can be found that all the aircraft targets have similar waveforms, as shown in Let F is shown as follows:The magnitude of As is shown in is large . MeanwhiIf making the circumferential sampling over every pixel in the image, the computational process is complex. To simplify this process, we construct an image convolution template, which is used to achieve the realization of Formula (2). The image convolution kernel can be designed as follows:The displayed formula consists of a radial function After the convolution operation on the RSIs, the response magnitude maps can be obtained. The response is the correlation of the circumferential gray value signal centered on a pixel and the circumferential gray value approximate signal of the aircraft target. As shown in Based on this fact, we introduce the mean-shift algorithm to cluster the points of the central connected region to generate the potential regions of the target. Compared with other clustering methods, the mean-shift algorithm does not require the specification of the number of clusters. The mean-shift algorithm was first proposed by Fukunaga and Hostetler , and it In this clustering process, the mean-shift clustering algorithm randomly selects a point as the initial center, and then iteratively finds the probability density maximum point along the direction of the increasing density gradient. The center of mass The mean-shift vector If There are significant differences in size between aircraft targets even in the same RSI. It is difficult to localize all targets with varying scales in the image for a single circumferential intensity convolution kernel. As shown in After obtaining the target center points by the method described above, the candidate regions can be obtained by framing operation. The size of bounding boxes is determined in the experimental part of In general, the feature extraction operation is to encode the discriminatory information in candidate regions. The features are then fed into a trained classifier for classification, which discriminates between actual targets and false alarms. The rotation of the aircraft can also bring significant differences in the feature representation. The common feature description methods perform poorly, such as the features based on the targets’ color, shape, textures, etc. Therefore, Liu et al.  proposedThis original Fourier HOG descriptor is a pixel-wise feature extraction method of candidate regions, which generates a high dimensionality of features. This can cause problems in the classifying process and may also have the risk of causing memory overflow. We introduce the VLAD encoding method to improve it, which not only reduces the dimensionality of the features effectively but also transforms the original features into higher-level features with statistical properties. The efficiency and accuracy of the classification process are improved.Histogram of oriented gradients (HOG)  has provThe HOG feature is a merged grouping of pixel gradients in an image based on orientation angles, producing a histogram of gradients in discrete directions. The histogram undergoes complex changes as the image rotates. While Fourier HOG feature uses a continuous representation in the gradient direction by creating an orientation distribution function and Φ(d) :(6)h(φ)=The distribution function Limiting the value of the maximum frequency order Thus, a series of complex coefficient images can be generated based on the gradient images. An example of this expansion is shown in A series of basis functions are constructed to do convolution with the gradient Fourier coefficient map and get the convolution result Based on the derivation of the literature , a rotatThe aforementioned Fourier HOG feature creates an orientation distribution function on each pixel and is obtained by convolution in full image. The final generated features are pixel-wise, and with a lot of non-discriminative and redundant information.The VLAD representation is a popular image coding method, which can aggregate descriptors into a fixed-size dimension based on a local aggregation principle in feature space. The representation method is first proposed by Jegou , and it The idea of VLAD is similar to BoW. The extracted local features are first clustered into several groups. The classical BoW approach is represented by a histogram, and the value of each bin is the number of features belonging to each particular group. While the VLAD method is a vector of residuals sum between the center of mass of each group and the local features belonging to that group.The VLAD representation of the Fourier HOG feature consists of the following steps. As shown in Then accumulating the difference between the center of each cluster and its contained descriptors subsets to obtain the vector:The final feature descriptor The images in the test set are also extracted to get their Fourier HOG features and then represented in the feature space using the codebook formed by the training set.In this section, experiments are conducted to validate the performance of the proposed aircraft target detection method. First, we give a brief description of the dataset used in the experiments and then identify some key parameters of the region proposal method. Finally, the effectiveness of the overall detection framework is verified by comparing it with other commonly-used methods. All the experiments were implemented on the platform of Intel Core i7-10700F @2.90GHZ CPU and 32 GB RAM.The optical RSIs used in this paper are derived from the RSOD dataset, which contains 446 remote sensing images with a total of 4993 aircraft targets. The sizes of the images are 1072 × 975 and 1116 × 659. Those images are from Google Earth and Tianditu, whose spatial resolutions range from 0.5 m to 2 m. Please refer to ,36 for mIn our experiments, 60% of the image samples are assigned as the training set, and the rest are assigned as test sets. In the training set, images are randomly selected to determine the size of the candidate regions, as well as to evaluate the performance of the candidate regions extraction.TP denotes the number of true positive aircraft recognition targets, FP denotes the number of false positive aircraft recognition targets, FN denotes the number of false negative aircraft recognition targets.To evaluate the performance of the proposed method, the intersection-over-union (IoU) between detection result and ground truth is adopted in this paper. When the IoU is greater than or equal to 0.5, the detection result is considered to be correct. We use the Precision-Recall curve (PR curve) and Average Precision (AP) to assess the performances of the proposed overall aircraft detection framework. The precision and recall are calculated with the following formulas:r represents recall and p(r) represents corresponding precision in the PR curve. Then the AP can be calculated:Average Precision (AP) is a measure that combines recall and precision for ranked detection results. AP computes the average precision value for recall value over 0 to 1. Namely AP is the area under curve (AUC). Let Based on the description above, the center points of potential aircraft target regions can be obtained by circular intensity filtering and a series of operations. Taking these points as the center points of the bounding boxes, the candidate regions can be obtained by cutting into several image patches with certain specific sizes. The size of bounding boxes has a significant impact on the accuracy of target detection. Because too large size will result in a patch containing too much background interference, and too small size will result in incomplete aircraft structure. To determine the proper size of bounding boxes, we analyze the long side of the target ground truth in the training dataset.To facilitate feature extraction and classification, aircraft targets are generally discussed in square form . As show0 = 0.3, t1 = 0.3, t2 = 0.5 is a trade-off result between recall and candidate regions number.We construct image pyramids of the original RSIs at three different scales, and the convolution kernel combining the radial function and 4th order circular harmonic function. Set the radius of the convolution kernel to 5. The convolution operation is performed on each layer of the image pyramid to get the response magnitude map pyramid. To remove the background interference in the image to get the true aircraft target center, it is necessary to perform threshold segmentation on each scale. An overly high threshold will filter out the true targets that are available, making the recall rate lower. A too low threshold retains a large number of false alarm centroids, giving burden on the later classification stage. The recall of the region proposal stage has a direct influence on the final detection performance. We conduct experiments on the region proposal stage with the different combinations of three thresholds, which is used in three levels RSIs pyramid. The results are shown in The proposed region proposal method based on circular intensity filter is compared with the two most popular region proposal methods including the EdgeBoxes algorithm  and the To quantitatively evaluate the performance of the overall detection method, we compare several state-of-the-art methods related to our proposed framework, such as ACF-based , and twoAccording to The visualization of detection results in the testing set is shown in Recently, deep learning methods have achieved great success in various tasks in remote sensing. It is inescapable that deep learning methods requires large amount of labeled training data and the support of specialized processing platforms like GPUs. Based on a small sample dataset, we propose a novel aircraft detection method on the basis of traditional machine learning VJ architecture, which provides a simple and easy idea to implement.In the region proposal stage, we introduce the idea of correlation filtering to construct a circular intensity filter to do fast convolution with the whole RSI. The convolutional response at the center of the aircraft is much higher than the other positions. So that the candidate regions can be extracted quickly. According to In the target identification stage, namely the fine screening stage, we apply the sparse representation method VLAD to improve the rotation-invariant Fourier HOG feature. According to the O(NM), where N is the pixel number of the circular intensity convolutional template. The complexities of threshold segmentation and mean-shift clustering are O(M), O(Tn2), respectively, where T is the number of iterations, n is the number of pixels of 1 in binary image. The complexity of the region proposal stage is O(NM) + O(M) + O(Tn2). Assume that an image patch generated by region proposal stage has m pixels. The complexity of the Fourier HOG feature extraction is O(skmn), where s is the scale factor of the basis function, k is the order of the basis function, and n is the pixel number of the basis function convolutional template. The complexities of VLAD and linear SVM (except for the offline learning process) are O(2KD(p+1)) [O(d) [O(skmn) + O(2KD(p + 1)) + O(d). In the future, we will focus on hardware acceleration strategies to improve the detection speed.We have calculated the computational complexity of the method. Given an RSI image with M pixels, the complexity of the filtering is KD(p+1)) , O(d) [4)) [O(d) , respectAircraft target detection in RSIs is a challenging problem due to the complex background and the variation of target size and direction. In this paper, we propose a novel aircraft target detection framework in which a region proposal method based on the circular intensity filter is constructed to locate potential multi-scale aircraft targets in RSIs. Moreover, we use the VLAD method to represent the rotation-invariant Fourier HOG feature, which has the lower dimensionality and the stronger description ability insusceptible of the target’s rotational behavior. Compared with other popular methods, the proposed method produces fewer high-quality candidate regions, while the overall detection method has better performance and is more robust to aircraft deformation. In future work, we will focus on small target detection, and improve the method to reduce the impact of uneven illumination and occlusion.