Closed airflow system, CUSP, for preventing SARS-CoV-2 infection, promoting health care, and achieving Sustainable Development Goals

Thorough analytical investigation is made on an open airflow system, on which conventional clean rooms are based, and on a closed airflow system realized by a clean unit system platform (CUSP) combined with a gas exchange membrane (GEM). The air pressure inside the CUSP is exactly the same as that outside. Thanks to this equal pressure in and outside of the room, there is no airflow coming and going across the GEM, resulting in a closed airflow system. In the CUSP/GEM system, fresh air is introduced, not by mechanical ventilation that conventional clean rooms are based upon, but by diffusion-based molecular ventilation, in which O 2 , CO 2 , and other molecules come and go across the GEM depending on the molecule concentration gradient across the GEM. Since there is no airflow exchanged between the inside and outside, together with the fact that microbes, having roughly two orders of magnitude larger size than molecules, are too large to diffuse across the GEM, the CUSP/GEM system can be an ideal, extremely safe place in which to protect people from SARS-CoV-2 or any other viruses floating in the air outside. The CUSP is an ideal place in which patients can be treated while staying in very clean air — importantly, with zero risk of any harm coming to people outside of the space. Based on this system, we have succeeded in demonstrating that CUSP can provide the opportunity of correlation analysis in sleep assessment with CO 2 production while patients are sleeping in the CUSP. The unique features of the CUSP/GEM system, that make the inside of the room completely decoupled from the outside, mean that it can effectively be used for various applications. In the near future, diffusion-based molecular ventilation, or molecular ventilation in short, will prevail with CUSP systems wherever fresh clean air is needed for any closed space.


Introduction
In the third industrial revolution, 1) the development of computers and electronic technologies has produced some new demands.Since the emergence of the steam engine, the use of fossil fuels has greatly accelerated the development of the industrial revolution, and new technologies have emerged one after another; however, pollution of the air has unfortunately also begun.For the electronics manufacturing industry, the production of electronic components, especially of large-scale ICs, needs to be carried out in a highly clean (dust-free) environment to improve the yield. 2)On the other hand, due to the long-lasting consumption of fossil fuels in the industrial revolution, a large amount of carbon dioxides, sulfides, nitrides, and incompletely combusted particulates have been discharged into the atmosphere, posing a great threat to the environment and people's health. 3)In the 21st century, the acceleration of carbon emissions has made people pay attention to the increasing need for environmental protection, in particular carbon neutrality. 4)According to the World Meteorological Organization, the 21st century needs to be an era of clean energy and reusable products. 5)Further attention has been paid not only to development, but also to sustainability.Indeed, clean water is important, as listed in the Sustainable Development Goals (SDGs), 6) but a clean air environment is indispensable.
A clean environment is also favorable for health care issues, and, in many cases, much needed.There are reports showing that the increase in particulate matter in the air increases the risk of cardiovascular and cerebrovascular diseases. 7,8)Around the world, as of October 2022, the SARS-CoV-2 pandemic caused more than 630 million cases and 6.5 million deaths. 9)The large number of confirmed cases brought a great load to the medical system of various countries, and a large number of patients could only be treated at home.The risk of family members becoming infected has increased. 10)It is mainly transmitted through droplets from the patient's cough or sneeze.Under such circumstances, how to reduce the risk of infection is critical.For patients recuperating at home, the first thing to do would be to avoid intra-family infection during home quarantine.To ensure safe air quality, it is necessary to have a good ventilation system, but a negative pressure system, such as those in hospitals, is too large to install in the home for family quarantine.It should also be noted that it is easy for particulate matter in ambient air to enter rooms under air circulation, which is not appropriate for the recovery of damaged respiratory systems and lungs. 11)Now, we need a new, less demanding, yet highly efficient clean system.The conventional ventilation systems are open airflow systems.Although we have known that the air is composed of gas molecules for some 200 years, 12) we have never taken advantage of this scientific knowledge; at least, not for ventilation.5]19) Then, in view of the other reasons why people might require a clean system, we have shown that it is possible to realize closedness and ventilation simultaneously.The CUSP-based clean environment can be used not only for industries, but also for patients of Covid-19, for example.Some CUSP systems are highly efficient compact clean spaces that can be easily set up when needed and removed when no longer required.CUSP-based systems can be transferred with agility to the next location wherever they are needed.We started developing CUSP, primarily, for uniting top-down and bottom-up systems, 19) and for the fabrication of semiconductor devices such as the highly efficient solar cells. 20)owever, we later realized that the CUSP could be used in a variety of fields, wherever cleanliness is needed in closed spaces.In this paper we will show analytically as well as experimentally how the CUSP is superior to conventional clean systems.We have succeeded in improving CUSP systems as an ideal clean space for treating Covid-19 and other infectious diseases, as well as for sleep assessment, and hopefully for improving quality of life (QoL), which, in turn, will help us achieve the holistic inclusive growth and well-being 21) outlined in the SDGs 6) in the near future.

Theoretical calculations of clean systems
When we tackle the issues listed in Sect. 1 by realizing a body-friendly indoor environment, we note that conventional clean systems are clearly insufficient.Good air quality should satisfy two aspects: (1) low levels of dust and bacteria/viruses in the air; (2) gas concentration control for the well-being and safety of people inside.Shown in Fig. 1 are a conventional clean room (or clean booth) and our CUSP system.The conventional clean system is equipped with a fan filter unit (FFU), which is composed of a fan with air-blowing ability and a dust removal filter.The FFU is located at the interface between the room (clean space) and the outside.The amount of airborne dust and/or microbes, including bacteria and viruses, is reduced by filtering the air from outside and pushing it into the room with the FFU.Eventually, the airborne dust and microbes in the room are pushed out by the clean air.In this system, the particles in the outdoor air continue to be collected by the filter, which starts to suffer from clogging, and the filtration efficiency decreases with time.It is a disadvantage of the conventional system that the FFU continues to get clogged even after the room itself has become sufficiently clean. 22)1.1.Airborne particles/microbes in conventional open airflow system.First, let us analyze the conventional system shown in Fig. 1(a).Assuming that the airflow through the ceiling is uniform and thus the particle/microbe density n is not dependent on the position in the clean space due to sufficient airflow, the dust density n at t = t + δt is given by The dust/microbe density inside the room increases in two ways: one is these coming out of the inner surfaces of what are inside (including the lungs of of individuals in the room) [the second term on the right-hand side of Eq. ( 1)] and the other is those coming inside through the filter with the incoming airflow (the third term) and decreases with being contained with density n in the outgoing air (the fourth term).Here, S is the area of the inner surface of the room shown in Fig. 1(a), V is the volume of the room, σ is the rate of dust particles coming out of the surface of the room (and people etc, inside, if any) per unit area per unit time, N 0 is the particle/microbe density outside, F is the airflow rate out of the FFU, and g is the dust filtration efficiency of the filter in the FFU.Equation (1) directly reads to the differential equation The solution to Eq. ( 2) is with the boundary condition n 0 ( ) = N , 0 i.e. the dust density inside is equal to the ambient dust density at t = 0, the time when the FFU is turned on.As seen in Fig. 1(a), the FFU catches the particles in the outdoor air but not those in the air in the room.The cleanliness is achieved just by expelling the particles in the in-room air outside with the clean air filtered by the FFU located at the interface of the inside and outside of the room.Thus, we may call it passive air filtration.
When we express the time dependence of n using the characteristic time, τ, as is given, from Eq. (3), as follows: From Eq. (3), we understand the presence of a scaling rule, which states that even if the size of a room is different, when F is increased or decreased in proportion to V, the identical time dependence of n can be obtained with the same characteristic time τ.Note that no matter how much time passes, the first two terms on the right-hand side of Eq. (3) remain in the conventional system, meaning that the conventional open airflow system is subject to the ambient particle/ microbe density N 0 forever.Of course, if a high-end filter with the filtration efficiency g being quite close to 1 is used, the influence from outside can be made very small [i.e.(1-γ) times N 0 ], but we have to remember that the finer the filter, the sooner it becomes clogged. 23)The filter lifetime is shorter.
2.1.2.Airborne particles/microbes in CUSP closed airflow system.To overcome the aforementioned hindrances of the old systems, we have been developing the proposed CUSP for decades, and the problems could be solved.The CUSP, as shown in Fig. 1(b), constitutes a 100% feedback system in which the entire amount of air outflowing from the FFU returns to the inlet of the FFU, resulting in a closed airflow system and also equal pressure inside and outside, because of which no airflow exists between the inside and outside of the room.As shown in Fig. 1(b), in our system, the FFU is isolated from the outside, which is in marked contrast to the conventional system in which the FFU is located at the interface between the inside and outside, as depicted in Fig. 1(a).In addition, it is an active filtering system in which the FFU traps the inside dust and/or microbes directly, which is again in marked contrast to the conventional system in which the FFU filters outside air, and this clean air pushes the inside particles and microbes out of the room, as shown in Fig. 1(a).This is a very risky way to obtain a clean room to treat Covid-19 patients, since the inside airborne particles and microbes, including SARS-CoV-2, can leave the room by being pushed out by the airflow driven by the FFU, since in the configuration of Fig. 1(a) the pressure inside is relatively positive compared to that outside.Thus, for the purpose of taking care of patients in a clean environment, indeed, the pressure inside is commonly set to be relatively negative compared to that outside, but with the air inside being then filtered out into the ambient air, the risk of people outside becoming infected cannot be zero since γ is close to, but not equal to 1.
In our CUSP, on the other hand, thanks to the closed airflow system enabling isolation from outside, the individuals inside are completely free from the risk that airborne microbes come into the room from outside.In addition, the in-room FFU, filtrating the inside air, operates virtually loadfree once the room is clean, and the filter clogging accordingly becomes negligibly small.As mentioned before, because there is no airflow between the inside and outside of the room, the SARS-Cov-2 that floats in the air cannot go inside from outside or go outside from inside, which makes the CUSP a ideal clean space to protect and treat Covid-19 patients staying inside, while keeping the people outside quite safe from any airborne viruses inside.
Let us analyze the dust density in CUSP in detail quantitatively.From Fig. 1(b), the dust density n at t = t + δt is given by Note that N o in Eq. ( 1) is replaced with n(t) in Eq. (5a), which is a direct result of the closed airflow of CUSP.The variation of dust/microbe density n with respect to time is simplified to Thanks to the fact that the CUSP is a 100% feedback closed air system, we can obtain Eq. 5(b) by just replacing N 0 in Eq. ( 2) with n(t).Equation 5(b) has the solution with the boundary condition of n 0 ( ) = N .0 For the closed airflow system of CUSP, the characteristic time is given by Because γ is close to unity, the characteristic time for a closed airflow system is almost the same as that of an open airflow system, with identical V and F. This scaling rule helps us build CUSP systems to fight against Covid-19.
In CUSP systems, when sufficient time passes, i.e. around t ∼ 10 × V/F, the second term on the right-hand side of Eq. ( 6) becomes negligible and the steady-state dust density is reached.The steady-state density is independent of the ambient particle density N o , in marked contrast to the case of the open airflow system, in which the steady-state density depends on N o forever, as shown by the second term in Eq. ( 3).This advantageous property is caused by the fact that the air is filtered inside the room, and the filter catches the airborne particles inside.Thus, we can call it active air filtration, in marked contrast to the passive air filtration in the conventional clean systems, for achieving high cleanliness.These characteristics show the superiority of the CUSP closed airflow system over the conventional open airflow system.The high cleanliness given by Eq. ( 8) can be obtained with the CUSP system no matter how large N 0 is, or how many particles or microbes are airborne in the ambient air outside the CUSP.
In CUSP, the key parameter governing cleanliness is completely different from that in conventional clean systems (rooms or booths).As Eq. (1) shows, the most important factor in the conventional clean room is γ, the filtering efficiency, which, of course, should be as close to 1 as possible for the sake of cleanliness.For this purpose, ultra-low particulate air (ULPA) and high-efficiency particulate air (HEPA) filters are used, but since one side of the filter is always exposed to the outdoor air, the main filter has to be replaced within years (even with the pre-filter) due to clogging. 24)For CUSP, on the other hand, the filtering efficiency g is not important at all, since a g as low as 0.9, for example, still demonstrates only 10% poorer cleanliness than the best cleanliness obtained with g = 1, as seen from Eq. ( 6).The most important issue for CUSP is to minimize σ as much as possible.To treat Covid-19, disinfection of the inner surface of what is inside of the CUSP room is important.

Gas concentration in conventional open airflow
system.In addition to the cleanliness, it is necessary to properly control the concentration of gas molecules of interest in a living space (room) with volume V.In the conventional clean system, ventilation is performed mechanically with an FFU that pushes the outdoor air into the room after filtration. 25)As shown in Fig. 1(a), the air in the room is replaced with the outdoor fresh air by the FFU, which results in mechanical ventilation.The conventional system is expressed quantitatively as follows.When oxygen-consuming activities (for example, burning of fire or breathing of people) are taking place at an oxygen consumption rate B [m 3 /s] in a room with volume V, letting t h ( ) and 0 h be, respectively, the oxygen concentration inside the room at time t and the oxygen concentration outside (the initial value of the indoor oxygen concentration), the volume of oxygen in the room at time t t t d = + is written as The first term on the right-hand side is the oxygen volume at time t, the second term is the increase in oxygen due to the ventilation with airflow F, () and the third term is the oxygen consumption, in the time interval (t, t + δt).From Eq. ( 9), transposing the first term on the right-hand side to the lefthand side and dividing both sides by t, d we obtain the differential equation Because at t 0 = the oxygen concentration is equal to , 0 h the solution of Eq. ( 10) is given by From Eq. ( 11), we find that the characteristic time t for controlling the gas concentration in the open airflow system is which is exactly the same equation as Eq. ( 4), although one is for particle reduction by filtration and the other is for gas concentration control.The reason the same equations hold for two different physical processes is because the functions of filtration and ventilation are spatially degenerated at the FFU, a direct result of which the characteristic times of those two physical processes are identical and governed by the single common parameter F. After sufficient time passes (around t ∼ 10 × V/F), the system reaches the steady state, the exponential part of Eq. ( 11) becomes almost zero, and the internal oxygen concentration converges to a constant value: Note that we can obtain the same result for the steady state just by letting dη(t)/dt = 0 in Eq. ( 10), taking advantage of being a steady state.
2.1.4.Gas concentration in CUSP closed airflow system.For the CUSP system, on the other hand, since it is an isolated closed system of equal internal and external pressures, as mentioned above, there is no airflow between the inside and outside.To introduce fresh air into the room, part of the wall of the room is made of gas exchange membrane (GEM), which is located at the interface between the inside and outside of the room, as shown in Fig. 1(b).Letting A be the area of this membrane, L the thickness, and D the diffusion coefficient of gas molecules across the GEM, the volume of oxygen in the CUSP room at time t t t d = + is given by where B [m 3 /s] is the oxygen consumption rate, N A is Avogadro's number, C is the gas volume per mole at the system pressure (∼1 atm.), and j is the oxygen flux coming into the room through the GEM.We now have the differential equation Note that since the air in the CUSP is well stirred by the independent parameter of airflow F generated by the FFU, the position dependence of t h ( ) can be neglected to a much better approximation than that in the conventional system for which F is directly connected to the ventilation as seen in Eq. ( 9).In CUSP, F is indeed a ruling parameter for reducing the rate of the particle counts, but not for gas molecule diffusion.The third term on the right-hand side in Eq. ( 14) is the volume of oxygen diffusing into the room due to the concentration gradient across the GEM (concentration difference between inside and outside of the CUSP).The flux j is given by where f is the number of gas molecules of interest (here oxygen) per unit volume inside the enclosure, D is the diffusion constant of the gas molecule across the GEM, and  is the differential operator in the direction perpendicular to the GEM.Since the thickness of the GEM, being extremely thin, is three or more orders of magnitude smaller than the size of the room, the derivative in Eq. ( 15) can be replaced, to a good approximation, by the difference in h divided by the thickness, and Eq. ( 15) leads to the differential equation where 0 h is the ambient gas concentration, which is about 20.9% for oxygen.With the same boundary condition as for solving Eq. ( 10), the solution for Eq. ( 17) is Now we understand the characteristic time t for controlling gas concentration in the closed airflow system is expressed as which is of course independent of F because the ventilation mechanism is completely different for the closed airflow system and the open airflow system, for which τ is given by Eq. (12).After a sufficient time, the gas molecule concentration is given by Comparing Eqs. ( 12) and ( 19), we have a very important equation of correspondence between the old-fashioned mechanical ventilation system and our new diffusion ventilation system: Thus, once a GEM with thickness L and a diffusion coefficient D for the gas molecule of interest is given, by adjusting the area of the GEM, we can realize a diffusion-based molecular ventilation system that has the same ability/performance of fresh-air introduction as any conventional ventilation system with airflow F, thanks to Eq. ( 19).In case there are plural gasmolecules of interest, and needed F is different for those gases, A is set according to the gas that needs the largest F for its sufficient ventilation, based on Eq. ( 19).

Feasibility check of CUSP using tent-type CUSP
Since the theoretical analysis has been done above, we can now implement CUSP/GEM systems based on the theory and check the performance.Thus, a tent-type CUSP (T-CUSP), shown in Fig. 2, is fabricated as one of the CUSP systems, in which the closed space is entirely covered by the GEM. 26)ere, a large area of GEM (∼8 m 2 ) is used as an airtight tent with a volume of ∼2 m 3 in Fig. 2. The FFU (Panasonic F-PDF35) has three adjustable levels of flow rates: ∼1.0, ∼2.0, and ∼3.5 m 3 /min, and γ of 0.95-0.98.For medical systems, especially for treating Covid-19, an extremely clean environment is indispensable.][29] For such cases, the CUSP could be the first choice, since the tent-type CUSP, being very easy to set up, does not consume too many resources, and it meets the requirements of cleanliness and low power consumption.When, in the near future, the CUSP is covered with flexible solar cells, the net power consumption of the whole CUSP system could be set close to zero.
Because of the global pandemic of SARS-CoV-2 and its sub-strains, an effective diagnostic environment that protects not only patients but also medical staff is indispensable.According to the regulations of the Ministry of Health, Labour and Welfare of Japan, the concentration of carbon dioxide (CO 2 ) in the room should be kept below 1500 ppm to ensure people's normal daily life.Also In this case, Eq. ( 20) helps us build a suitable CUSP/GEM system by letting B be negative (because CO 2 increases with burning) and setting A large enough to keep η(t) no greater than 1500 ppm with η o of 440 ppm, the background CO 2 concentration.The gas exchange unit (GEU) is composed of multiple GEMs stacked in a rectangular box, and it can guarantee uninterrupted ventilation throughout the day, through molecular diffusion that is driven by thermal energy at RT, thus, without turning on the FFU.As for the FFU in CUSP systems, since it does not exchange the airflow inside with that outside, the internal air environment keeps getting cleaner under 100% feedback with closed air circulation.The particulate matter in the air is quite low, and will have an almost negligible impact on people's lungs and cardiovascular and cerebrovascular systems.
The following experimental procedures are performed to verify the cleaning and gas exchange ability of the T-CUSP shown in Fig.  we plot the data point at 0.1/cf for the sake of clarity as zero goes to −∞ in the logarithmic plot).It takes about 10 min to reduce the particles/microbes inside by 1/10,000, reaching US FED STD 209E class10, equivalent to ISO 4, as shown by the pink line in Fig. 3, from which the time constant of decay of the particle count is about 1 min, which is in good agreement with the time constant expected from Eq. ( 3):  30) we can expect a higher filtration efficiency for SARS-CoV-2 viruses (as seen in Fig. 6, which we discuss later).Thus, the CUSP can provide us with a very good environment for treating Covid-19 and other respiratory diseases.

Gas concentration control experiment
For the gas molecule concentration control experiment, oxygen and carbon dioxide concentrations are monitored as a function of time in the compact CUSP, which has roughly the same volume (∼2.5 m 3 ) as the T-CUSP mentioned in Sect.2.2.The gas exchange in the compact CUSP is done with a GEU that is equipped with a GEM of ∼3 m 2 .As shown in Fig. 4, those concentrations are well controlled in the CUSP after a 16-minute-long combustion process.At the end of the combustion, the oxygen quickly begins to recover.Presumably due to the latent time of the cooling of the air inside the CUSP after the combustion, the carbon dioxide concentration gradually increases for a period of time before it starts to decrease.The carbon dioxide concentration reduces from 4000 ppm down to below 1500 ppm, and the oxygen concentration is restored to that of the ambient air within 30 min.The time constant, being almost the same for O 2 and CO 2 , is about 15 min, but strictly speaking it is larger for CO 2 than for O 2 , which is explained by the fact that the masses of CO 2 and O 2 molecules are, respectively, about 44 and 32 times the proton mass.From the time constant, using Eq. ( 19), the diffusion constant is estimated to be / since V, L, and A are 2.5 m 3 , 160 mm, and 3 m 2 , respectively, as mentioned above in Sect.2.2.This, we believe, is the first experimentally obtained diffusion coefficient for a sheet of unwoven fabric used as the GEM.The diffusion coefficient of oxygen in air is on the order of 10 −5 cm 2 /s. 31)Thus, the diffusion coefficient D that we have estimated for oxygen molecules in GEM is roughly two orders of magnitudes smaller than that in the air, which is quite reasonable to think of the density of the thin sheet of unwoven fabric being much larger than that of the air.

Application to sleep assessment
Now dust/microbe-free clean air and gas concentration control are achieved using the CUSP closed space, and we have applied the T-CUSP, shown in Fig. 2, to a sleep assessment experiment, since Covid-19 patients are mainly sleeping to restore their strength while being treated.Sleep is also important to maintain one's physiological and psychological well-being.However, sleep quality is often affected by many environmental factors, such as air particles, temperature, and noise.We utilize the T-CUSP to construct a high-air-quality sleep environment.A new form of noncontact sleep monitoring approach integrated with the T-CUSP is demonstrated.The T-CUSP provides a compact isolated closed system in which gas molecule concentrations can be controlled.Due to the fact that high cleanliness is maintained in the tent, it is feasible to measure the metabolism and sleep pattern of subjects in a non-contact manner.Humans breathe CO 2 into the surrounding environment, and it is the main source of CO 2 in the T-CUSP.Hence, we have proposed a flow for analyzing the correlation between CO 2 concentration and actigraphy during all-night sleep.For each 30 s epoch, if the measured CO 2 concentration increases over 20 ppm, the local maximum peak is detected and recorded.We check, based on the actigraphy score, if this epoch is during wake or sleep.An example of analyzing the correlation between CO 2 and actigraphy is shown in Fig. 5. 32) We observe six periods of CO 2 dioxide fluctuations, which  were synchronized with the wake stage of polysomnography (PSG) and actigraphy scoring.Also, quite recently, we developed a new type of CUSP called the Nap-box, in which people can take short naps in a standing position, 33) which demonstrates that the application of the CUSP/GEM system is quite useful and would be beneficial for improving QoL.

Discussion
For the safe use of clean rooms, we must assure that the oxygen concentration η(t) is always set higher than a critical concentration , c h of 18.5%, for example.Thus, Now, from Eq. ( 20), we have from which we have The left-hand side of Eq. ( 26), being the available oxygen volume inside divided by the oxygen consumption rate, is nothing but the time limit t c (for safe staying inside) in case there is no fresh air provided.As seen from Eq. ( 26), the lower bound of the time limit, VL/AD, is equal to τ in Eq. ( 19).Now, we can fully understand that the characteristic time τ for gas concentration control using GEM for the closed airflow system is exactly the same as the lower bound of the time limit t c .Moreover, when we rewrite Eq. ( 19) as we come to the full comprehension that the characteristic time and/or the lower bound of the time limit is determined by a fraction whose numerator (V/A) is solely determined by the inherent geometrical property of the room (V and A), and the denominator (D/L) is genuinely dependent on the GEM's intrinsic properties (D and L) only.Equation ( 27) is a concise, esthetic expression showing that the characteristic time τ is the ratio of the extrinsic property of the room to the intrinsic property of the GEM.
Based on the important result obtained using HEPA filters to reduce SARS-CoV-2 in hospitals, 34) we believe that the CUSP closed airflow system could perform even better.As shown in Fig. 6, ULPA has the highest purification efficiency, followed by HEPA, and ordinary masks or the medium-efficiency filters in commercially available homeuse FFUs have an insufficient filtration efficiency; however, the low-efficiency filters can outperform high-quality filters once they are embedded in our CUSP system.For the sake of simplicity, let us assume that γ of the low-efficiency filter is 0.9 for now.Then in a single pass, 10% of the particles/ microbes go through unfiltered, but when the air passes thorough the filter N times, the probability that the particles go through the filter is as low as 10 −N , because, CUSP being a closed airflow system, the same inside air goes through the filter repeatedly many times (N ?1).For example, in the system shown in Fig. 2, the air in the CUSP is filtered every 2-3 minutes, and as shown in Fig. 6 the filtration efficiency could be even better than HPEA (blue line) or ULPA (red line) when N > 5 or 6 (note that we have zero count in 10 min in Fig. 3).As seen in Fig. 6, particles with sizes of around 0.15 μm (in between 0.1 to 0.3 μm) are the most difficult to filter, but the SARS-CoV-2 in aerosol form of various sizes is much smaller than that, and is relatively easy

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© 2023 The Author(s).Published on behalf of The Japan Society of Applied Physics by IOP Publishing Ltd to filter thanks to the Brownian motion 35) of the particles caused by collision against, as well as scattering by, gas molecules comprising the air.
The GEM shows a performance good enough to ensure the user's/patient's day-and night-time ventilation in the tent at home.For many applications, however, we have to make the CUSP system compact as well as portable when required, and the portability and ease of setup have been realized using a type of CUSP named CAQLEA. 36,37)ow, a lot of data acquisition and analyses become possible thanks to the closed airflow of the CUSP/GEM system, as shown in Fig. 7. Indeed, such multi-layered analysis based on molecular-level description and higherlevel information has recently been shown to be powerful in transport processes across membranes in living organisms. 38)he first layer: As shown at the bottom of Fig. 7, molecules such as O 2 , CO 2 , CO, and also volatile organic compounds can be detected in the CUSP/GEM system as a layer of molecularlevel analysis.For patients with different symptoms, there are certain differences in the substances produced by their own metabolism and excreted from the body.
These effluent molecules are held inside the T-CUSP so that the detection of these characteristic molecules can be used to diagnose a patient's disease in a non-invasive manner.In particular, it is possible to detect the frequency and the amount of body motion while the user of the T-CUSP or other compact CUSP is sleeping in his/her usual manner wearing pajamas and a blanket, which are, unlike clean suits, a source of dust and particles, by detecting the increase in particle numbers while sleeping in the T-CUSP thanks to its closed airflow.
The second layer: Furthermore, in the middle of Fig. 7, a metabolism/energy-level analysis can be done.Based on the O 2 and CO 2 concentration measurement, when a subject is performing exercise in a compact CUSP/GEM (or GEU) system, we can tell whether carbohydrate or body fat is mainly consumed in his/her body based on the respiratory quotient.
The third layer: Finally, as shown at the top of Fig. 7, the functions of subjects residing in the CUSP/GEM (or GEU) system can be detected.As discussed above, sleep assessment has been performed in the CUSP systems. 32,33)As shown in Fig. 3, the T-CUSP provides patients with an ultraclean sleeping environment, which is important for curing their respiratory system, as well as evaluating sleep quality, as discussed above.
The CUSP/GEM system would help us achieve the holistic inclusive growth and well-being 9) outlined in SDGs 6) as an important and powerful infrastructure.Furthermore, this scheme can be applied not only for human beings but also for other living systems, which could lead to a new type of smart agriculture. 39,40)The closed airflow system is of huge potential interest for future agricultural industries as well as for health care industries.

Conclusions
We have made a thorough analytical investigation of the open airflow system, on which conventional clean rooms are based, and the closed airflow system, which is realized by a CUSP combined with a GEM.In the CUSP/GEM system, all of the filtered air coming out of the FFU, after circulating in the room, goes back to the inlet of the FFU.Since the room air is pushed at the outlet of the filter but is polled at the inlet of the same FFU, the pushing pressure is canceled by the pulling pressure, and thus the air pressure inside the CUSP is exactly the same as that outside.Thanks to this equipressure between the in-and outside of the room, there is no airflow coming or going across the GEM, resulting in a closed airflow system.In the CUSP/GEM system, fresh air is introduced, not by the mechanical ventilation that conventional clean rooms utilize, but by the newly introduced diffusion-based molecular ventilation, in which O 2 , CO 2 , and other molecules go across the GEM from the higher concentration side to the lower side.We realized a diffusionbased molecular ventilation system that has the same ability/ performance of fresh-air introduction as any conventional ventilation system.Since there is no airflow exchanged between the inside and outside, together with the fact that microbes having roughly two orders of magnitude larger size than molecules are too large to diffuse across the GEM, the CUSP/GEM system is an ideal, perfectly safe place to protect individuals inside when SARS-CoV-2 or other viruses are floating in the air outside.The CUSP is also an ideal place in which a patient can be treated while staying in very clean air, importantly, with zero risk that the patient does any harm to those outside.We also have succeeded in demonstrating that the CUSP can provide us with the opportunity of correlation analysis in sleep assessment with CO 2 production when a patient is sleeping in the CUSP.These unique features of the CUSP/GEM system promote the advancement of medical diagnosis.Based upon the three levels of analyses, the health status analysis paves the way for a better QoL.In the near future, diffusion-based molecular ventilation, or molecular ventilation in short, will prevail with CUSP systems wherever fresh clean air is needed for any closed space.

Fig. 1 . 2 ©
Fig. 1.(a) Conventional cleaning system, (b) CUSP.017003-2 2. (1) Completely mix the air in-and outside of the tent, so that particles can fully enter the internal space.Turn on the FFU and record the number of particles (one part per cubic foot) to verify the internal cleaning ability of the T-CUSP.(2) Ignite the cassette furnace inside a compact CUSP having roughly the same volume, GEM area and FFU as the T-CUSP.Turn it off after burning for a period of time, and measure the oxygen and carbon dioxide concentrations in the CUSP as a function of time.The gas concentration control ability of the GEM can be examined by monitoring the internal air conditions.3.Experimental results and discussion3.1.Airborne particle reduction experimentAs shown in Fig.3, 10 min after turning on the FFU, the number of PM0.5 and PM1 particles stabilized at a very low level.Although the number of PM0.3 occasionally fluctuated, the dust/microbe density decreased down to zero (note that

Fig. 2 . 5 ©
Fig. 2. (a) Conceptual diagram of T-CUSP; (b) inside view of T-CUSP, the air purifier works uninterrupted when people are present, gradually reducing the amount of particle matter.The observation window provides experimental personnel with conditions for medical observation, and the real-time cleanliness and gas concentration can be seen.(c) Object in T-CUSP.017003-5

Fig. 3 .
Fig. 3. Particle/microbe counts as function of time in T-CUSP.The solid diamonds, squares, and triangles denote particle counts with diameters of, respectively, 0.3 μm, 0.5 μm, and 1.0 μm or larger.The particle count 0 is plotted at 0.1 for the sake of avoiding −∞.

Fig. 4 .
Fig. 4. Changes in O 2 and CO 2 concentration: blue circles show O 2 and red show CO 2 .

Fig. 5 .
Fig. 5.An example of analyzing the correlation between CO 2 and actigraphy.The sudden increase in CO 2 concentration clearly reflects a waking stage with large body movements.The horizontal axis shows the number of epochs (1 epoch = 30 sec).

Fig. 6 .
Fig.6.Filtration efficiency and transmissivity for different filters.Green line is for a medium-efficiency filter with γ ∼ 95%, blue line for HEPA filter with γ ∼ 99.97%, and red for ULPA filter with γ ∼ 99.9995%.

Fig. 7 . 8 ©
Fig. 7. Multi-layered approach for improvement in health enabled by closed airflow system.