General introduction 1.1 Introduction Humans have always envisioned swimming like a fish. Throughout history, having enviously watched the fishes swimming in water and breathing through their gills, humans have always longed for a device that functions as gills. In the past century, several underwater swimming and diving equipments were developed. One of these equipments was an oxygen-supplying device that supplies oxygen from the atmosphere to an underwater diver through a hose. This air-pumping hose limits the diver’s area of free movement, and in most cases, it entangles, thereby resulting in several accidents. In recent years, scuba-diving equipment bearing tanks of compressed air or oxygen was developed. This device is referred to as an “aqualung” and is widely used for recreational purposes since it eliminates the entangling of air pipes and provides complete freedom of movement. However, after exhaustion of the compressed air or oxygen in the tanks, the diver must return to the surface. These previously developed equipments have not attempted and succeeded in providing any equivalent to fish gills, whereby dissolved oxygen is extracted from the water and whereby carbon dioxide is disposed of by passing it to the water. Humans, hence, tried to develop the device that takes up oxygen from water like a fish gill. The device, which is called “artificial gill”, has been studied by several researchers, and several artificial gills were developed. However, these artificial gills have not yet practical, because the oxygen transfer rate form water is not adequate, and the oxygen partial pressure provided in the air is too low for human respiration. In the present thesis, novel artificial gills that efficiently transfer oxygen from water to air were developed on the basis of methodologies in chemical and 2
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General introduction 1.1 Introduction
Humans have always envisioned swimming like a fish. Throughout history,
having enviously watched the fishes swimming in water and breathing through
their gills, humans have always longed for a device that functions as gills.
In the past century, several underwater swimming and diving equipments
were developed. One of these equipments was an oxygen-supplying device that
supplies oxygen from the atmosphere to an underwater diver through a hose.
This air-pumping hose limits the diver’s area of free movement, and in most
cases, it entangles, thereby resulting in several accidents.
In recent years, scuba-diving equipment bearing tanks of compressed air or
oxygen was developed. This device is referred to as an “aqualung” and is widely
used for recreational purposes since it eliminates the entangling of air pipes and
provides complete freedom of movement. However, after exhaustion of the
compressed air or oxygen in the tanks, the diver must return to the surface.
These previously developed equipments have not attempted and succeeded
in providing any equivalent to fish gills, whereby dissolved oxygen is extracted
from the water and whereby carbon dioxide is disposed of by passing it to the
water. Humans, hence, tried to develop the device that takes up oxygen from
water like a fish gill. The device, which is called “artificial gill”, has been
studied by several researchers, and several artificial gills were developed.
However, these artificial gills have not yet practical, because the oxygen transfer
rate form water is not adequate, and the oxygen partial pressure provided in the
air is too low for human respiration.
In the present thesis, novel artificial gills that efficiently transfer oxygen
from water to air were developed on the basis of methodologies in chemical and
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biomedical engineering. These gills enhanced the oxygen transfer from water to
air and provided high oxygen partial pressure in air, which was suitable for
human respiration. This thesis would be a step toward the realization of artificial
gills and the fulfillment of the dream of swimming under water.
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General introduction
1.2 Conditions for designing an artificial gill
The artificial gill is a device that transfers oxygen from water to underwater
divers. Hence, the artificial gill is designed based on human respiration and
oxygen concentration in seawater. The oxygen consumption rate in humans
determines the required oxygen transfer rate from water to air, and the oxygen
concentration in seawater determines the required flow rate of seawater and the
driving force for oxygen transfer. The conditions for designing the artificial gill
are described in this section.
1.2.1 Supply of oxygen and removal of carbon dioxide
The most important function of an artificial gill is to supply oxygen. The
amounts of oxygen consumption and carbon dioxide production in human
respiration are 250-300 cm3/min and 200 cm3/min, respectively [1,2]. These
values increase more than 10 times during physical exercise. The minimum
required oxygen partial pressure during inspiration is 13.3 kPa; however, for
stable breathing, a pressure greater than 17.3 kPa is desired. It is known that a
very small concentration of carbon dioxide is required during inspiration. Since
the central nervous system is sensitive to carbon dioxide, a carbon dioxide
concentration higher than 0.1% could pose serious problems [1].
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1.2.2 Oxygen concentration in seawater
For designing an artificial gill, knowledge regarding the oxygen
concentration in seawater is important because the required flow rate of
seawater and driving force of oxygen uptake vary with a change in the oxygen
concentration (oxygen partial pressure). Seawater contains several gases such as
nitrogen, oxygen, carbon dioxide, etc. As shown in Fig. 1.1, the concentration of
oxygen and carbon dioxide in seawater vary with water depth. Oxygen is
absorbed from the atmosphere and spreads throughout seawater by convection.
In addition, photosynthesis of seaweeds also contributes to the oxygen content in
seawater. Oxygen concentration is constant at approximately 5-6 cm3/m3 (STP)
at a depth of up to 100 m. In the depth zone, oxygen concentration decreases
with increasing water depth because oxygen is consumed during respiration by
sea animals and seaweeds. Carbon dioxide concentration is also constant at 46
cm3/m3 (STP) at a depth of up to 100 m, and it increases with water depth
greater than 100 m [1,3].
Fig. 1.1 Oxygen (a)
(a)
and carbon dioxide (b) con
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(b)
centrations in seawater
General introduction
1.3 Previously developed artificial gills
Several artificial gills have been developed by researchers in the field of
chemical engineering and medical science. First, a prototype of the artificial
gills was developed using a gas permeable membrane. Next, novel artificial gills
were developed using an oxygen adsorbent and an oxygen carrier solution.
These artificial gills possess certain characteristics for transporting oxygen from
water to air. The characteristics of these artificial gills are described in this
section.
1.3.1 Membrane-type artificial gill
In one of the earliest studies on artificial gills, Ayres developed artificial
gills using a flat silicone membrane that only permeated gas and not water [4].
The expired air came in contact with water through the membrane, and the
oxygen dissolved in water was transferred to the expired air through the
membrane. This transfer was driven by the oxygen partial pressure difference
between water and expired air. Carbon dioxide was also transferred from expired
air to water, as shown in Fig. 1.2. This type of artificial gill is termed
“membrane-type artificial gill.” Bodell reported a gas permeable apparatus with
coils of capillary tubes made of silicone rubber with a length of 600 m, as shown
in Fig. 1.3; this apparatus could keep a rat alive for 25 h [5,6]. Paganelli et al.
reported artificial gills developed using a porous membrane. At an oxygen
partial pressure of 13.3 kPa in air, the required membrane surface areas were 8
m2 at rest and 80 m2 during exercise [7]. Yang and Cussler [8] developed an
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artificial gill using hollow fiber membranes composed of porous polypropylene.
They successfully kept a dog alive by using this artificial gill. Matsuda and
Sakai designed an artificial gill module consisting of a hollow fiber membrane
by computer analysis [9].
Over the years, gas permeability of the membrane has been greatly
improved. Thus, a greater portion of oxygen transfer resistance of the
membrane-type artificial gills is located on the waterside of the laminar film.
Hollow fiber arrangement and module structure were improved by disrupting the
water flow to decrease the laminar film resistance [7-9].
However, the oxygen transfer rate from water to air obtained using either
the hollow fiber arrangement or module structure is not sufficient for human
respiration because of the small driving force involved in oxygen transfer, which
is the oxygen partial pressure difference between water and air. Furthermore, the
oxygen partial pressure provided in air is significantly lower than that in
seawater [7]. Therefore, a large membrane surface area and device volume were
required to apply these models to humans.
Fig. 1.2 Partial pressure profiles of oxygen andcarbon dioxide in membrane-type artificial gills
Fig. 1.3 Artificial gills using capillary tubes composed of silicone rubber [5]
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General introduction
1.3.2 Adsorbent-type artificial gill
Bonaventura et al. developed an artificial gill using an oxygen adsorbent,
which was made by immobilizing hemoglobin in porous polyurethane (Fig.
1.4), and they increased the oxygen transfer rate from water to air [10]. The
oxygen adsorbent was termed “hemo-sponge.” Oxygen was adsorbed by the
contact of water with the hemo-sponge and released by changing the pH. It was
possible to supply highly concentrated oxygen with this artificial gill. Shimada
et al. developed the same system using a photo bridge formation matrix and
hemoglobin [11]. Oxygen was released into the air by the oxidation of
hemoglobin. The oxygen adsorbent has a film structure, which results in rapid
oxygen adsorption as compared to that on hemo-sponge. On the other hand, an
artificial gill was developed by circulating nitrogen gas and using an adsorbent
[12-17]. Oxygen was transferred to nitrogen gas through a membrane with large
oxygen partial pressure difference (driving force) and was concentrated using an
adsorbent. However, these artificial gills were not portable because a large and
complicated apparatus was required to dissociate oxygen from the oxygen
adsorbent.
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Fig. 1.4 Adsorbent-type artificial gill [10]
Fig. 1.5 Adsorbent-type artificial gill fabricated with a gas permeable membrane and by circulating nitrogen gas [12-17]
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General introduction
1.3.3 Oxygen carrier solution type artificial gill
Haramoto et al. developed an artificial gill using two hollow fiber
membrane modules and an oxygen carrier solution [18,19].
Perfluorooctylbromide (PFOB), one of the perfluorocarbons, was used as the
oxygen carrier solution. Oxygen was absorbed from water into the oxygen
carrier solution through one module and released into expired air through the
other module (Fig. 1.6). The oxygen solubility of PFOB is approximately twenty
times larger than that of water. Therefore, the oxygen carrier solution served as
an oxygen storage tank during oxygen shortage in seawater.
Matsuda et al. developed an artificial gill using red blood cell suspension as
a thermoresponsive oxygen carrier solution [20,21]. Fig. 1.7 shows the artificial
gill with the circulation of an RBC suspension. During oxygen uptake from
water to the oxygen carrier solution, the oxygen carrier solution was cooled to
293 K. This enhanced oxygen uptake because the oxygen affinity of red blood
cells was increased due to cooling. During the release of oxygen into the expired
air, the oxygen carrier solution was heated to 310 K. In this case, the oxygen
release was enhanced because the oxygen affinity of red blood cells decreased
with heating.
This artificial gill system significantly enhanced oxygen transfer from water
to air. The oxygen transfer performance of these artificial gills depends on the
oxygen carrier solution. Hence, these artificial gills require a novel oxygen
carrier solution that provides high oxygen carrying performance for an optimal
operating condition.
In this thesis, the novel oxygen carrier solutions were developed, and an
optimal operating condition was determined to transfer oxygen more efficiently.
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Fig. 1.6 PFOB circulating type artificial gill [18]
Fig. 1.7 Artificial gill with the circulation of an RBC suspension [20]
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General introduction
1.3.4 Clarification of the fish gill mechanism and its application to artificial gill
A fish can exchange gases effectively by the indirect contact of blood with
water in its gills. A comparison of respiration in fishes and humans is shown in
Table 1.1. For example, water contains a small amount of oxygen as compared
to air, and the oxygen diffusion rate in water is smaller than that in air. It would
be useful to elucidate the mechanism of a fish gill for developing an efficient
artificial gill.
Table 1.1 Comparison of respiration in fishes and humans [22] Fishes Humans
Structure of respiratory organs Gill filament Alveoli
Ventilation Single pass Tidal movement Circulation Counter current flow Complex mixed flow
Respiratory medium Water Air Body temperature Variable Constant
O2 pressure of inspired medium 1-200 mmHg 80-100 mmHg CO2 pressure of inspired medium 0-3 mmHg 40-45 mmHg
O2 diffusion rate Low (in water) High (in air) O2 capacity of the medium Low High
Density of the medium High Low
Hazelhoff and Evenhuts [23] reported the importance of water flow
direction in fish gills. Water was made to flow in the same as well as opposite
directions to blood flow in the fish gill. Further, oxygen utilization in water was
obtained by measuring the oxygen concentration at the inlet and outlet of the
fish gill. The utilization in the opposite direction was found to be larger than that
in the same direction. This suggested that water and blood flow are in opposite
directions in fish gills. This countercurrent system is important for effective
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oxygen uptake in fish gills.
Mizoguchi et al. [24] observed fish gills with a fiberscope and measured
water flow velocity in the vicinity of the gill filament. The linear velocity of
water in the vicinity of the gill filament was 5 cm/s. The water flow in the
buccal cavity was in one particular direction; however, it was disturbed in the
vicinity of the gill filament. They suggested that the turbulent flow in the
vicinity of the gill filament disrupts the waterside film resistance and enhances
oxygen uptake from water.
Matsuda and Sakai [9,21] evaluated the secondary lamella of fish gills by
computer simulation analysis. They established a secondary lamella model, as
shown in Fig. 1.8. They found that waterside and blood side film resistances
were small because the water and blood paths were remarkably narrow, and the
oxygen transfer across the biological membrane is a rate-determining step for
oxygen transfer through the secondary lamella.
Fig. 1.8 Secondary lamella model established by Matsuda and Sakai [9,21]
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General introduction
1.3.5 Controlled Ecological Life Support System with artificial gill
The Controlled Ecological Life Support System (CELSS) has been studied
for its application to space exploration. It is an ecological system in which
several creatures coexist in a closed system such as a space station. An artificial
gill system was used to exchange respiratory gases between the algae cultivation
tank and animal habitation space. As shown in Fig. 1.9, oxygen is produced by
photosynthesis in cultivated algae and is supplied to the animal habitation space
through an artificial gill module. In contrast, the expired carbon dioxide from an
animal is transferred to the algae cultivation tank, and carbon dioxide is used in
photosynthesis by the algae.
Bowman and Thomae [25,26] were successful in sustaining a mouse for 66
days in a closed chamber. Oxygen that was produced due to photosynthesis in
the algae was supplied from the algae cultivation chamber through a gas
permeable membrane. Mastumoto et al. designed a water-water CELSS in order
to culture fish [26-28]. They demonstrated that it was possible to exchange
dissolved oxygen and carbon dioxide between the aqueous phases in algae
cultivation and fish habitation tanks in opposite directions by the contact of
these phases in an artificial gill module.
Fig. 1.9 Schematic of a Controlled Ecological Life Support System (CELSS)
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1.4 Relevant study for artificial gill
Several relevant studies provide hints on further improvement of the
artificial gill, such as the study on the blood oxygenator, hollow fiber module,
blood substitute, oxygen carrier complex, gas separation, etc. For example, a
blood oxygentor possesses the ability to enhance oxygen transfer to venous
blood, and a blood substitute can carry oxygen to tissues. These characteristics
are useful for developing a more efficient artificial gill.
1.4.1 Blood oxygenator and hollow fiber module
The blood oxygenator, referred to as “artificial lung,” is a device that
supplies oxygen to venous blood. It replaces the pulmonary function during
cardiac surgical procedures that require cardiopulmonary bypass. In the past,
several cardiac surgeons used a bubble oxygenator [30] and a film oxygenator
[31], which enable direct contact of venous blood with oxygen (Fig. 1.10).
These oxygenators cause significant blood damage because of exposure to
oxygen gas. Hence, a membrane oxygenator, which transfers oxygen to venous
blood through a hollow fiber membrane, is widely used at present because of its
excellent blood compatibility [32-34]. These membrane oxygenators use hollow
fiber membranes, such as porous polypropylene, having high gas permeability
[35-46]. The rate-determining step of oxygen transfer is located at the blood side
boundary layer because the membrane and oxygen gas-side resistances are
negligibly small as compared to the blood side resistance [35,47].
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General introduction
Thus, various hollo
resistance. A blood
1.11) [47-56] and fo
was developed to
researchers demons
are perpendicular
[72-77]. Currently,
arrangement. In an
solution, flowing o
oxygen transfer to
blood oxygenator m
artificial gill.
Fig. 1.10 Film and bubble oxygenators [30,31]
w fiber modules were designed to disrupt the blood side
oxygenator for blood flowing into coiled hollow fibers (Fig.
r blood flowing outside the hollow fibers (Fig. 1.12) [57-71]
enhance the oxygen transfer. After several attempts, some
trated that a hollow fiber module in which the hollow fibers
to blood flow exhibit a high gas exchange performance
almost all membrane oxygenators use this hollow fiber
artificial gill, a fluid, such as seawater or oxygen carrier
utside and perpendicular to the hollow fibers may enhance
or from the outer hollow fibers. The theory of designing a
ay be useful to optimize the hollow fiber arrangement in the
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Chapter 1
Fig. 1.11 Blood oxygenator for blood flowing into coiled hollow fibers [49]