Jpn J Extra-Corporeal Technology 46（2）：119 − 124, 2019

Effects of bubble size differences on the bubble-trapping
performance of arterial line filters
Atsushi Nakamura，Masahiro Kikuta

Abstract
Microbubbles inside a cardiopulmonary bypass circuit are captured by a venous reservoir or by the artificial
lung, and ultimately, an arterial line filter (ALF) prevents gaseous micro-emboli (GME) from getting injected into
the patient’s body. In our study using ALFs with pore sizes of 40 μm ( PS40) and 20 μm ( PS20), bubbles with amean bubble diameter of 50 μm, 100 μm, and 180 μm were injected into the ALF. Arterial line filter GME removal was examined using different bubble sizes.
In the bubble group with various bubble sizes, the number of bubbles and the rate of bubble removal were determined for 50 μm bubbles ( PS40＝44.5±0.7％, PS20＝56.1±0.6％, P<0.001), 100 μm bubbles ( PS40＝13.7±1.9％,
PS20＝9.9±3.8％, P＝0.205), and 180 μm bubbles (PS40＝－7.0±1.5％, PS20＝－29.3±1.8％, P<0.001). Air bubble shrinkage and bubble volume removal rates were significantly higher with PS20.
The bubble’s internal pressure becomes lower as the bubble size is larger, which suggests that air bubbles caneasily change shape and disrupt. This suggests that GME removal capability increases when all microbubbles thatflow into the ALF are maintained at a diameter of 40-50 μm or less.
Key words：gaseous microemboli (GME)，microbubbles，bubble trap performance，arterial line filter

Ⅰ．Introduction

circuit to prevent microbubbles from being transport-

One reason that cardiopulmonary bypass (CPB) is

ed into the body. However, according to a report oninvasive for the body is the gaseous micro-emboli

GME removal for CPB circuits, bubbles larger than(GME) in, for example, thin blood vessels such as thethe ALF pore size have been confirmed at the exit

capillaries and cerebral and peripheral blood vessels.

site of the ALF 2). An increasing number of GMEs

Microbubbles during a CPB can be caused by drug

have been found to have been detected after passing

administration, collection of blood samples, suction inthrough the ALF, and results have shown that many

the surgical field, or other events . When microbub-

GMEs pass through the ALF 3-6). These research re-bles are mixed in the blood, they can cause an em-

sults suggest that the capacity for GME removal isbolus in thin blood vessels, with the potential danger

affected by the size of the bubbles flowing into theof vascular damage or brain dysfunction. Bubbles in

ALF；however, how different bubble sizes affect the

the CPB circuit are captured in the venous reservoir,

capacity for GME removal remains unclear.

1)

the artificial lung, or elsewhere, and an arterial line

Therefore, in the present study, bubbles of three dif-filter (ALF) acts as the last line of defense in the CPB

ferent sizes were used on ALFs with pore sizes of 40○Department of Clinical Engineering, Faculty of Health Sciences, Kyorin University
Corresponding Author：Atsushi Nakamura
Department of Clinical Engineering, Faculty of Health Sciences, Kyorin University
5-4-1, Shimorenjaku, Mitaka, Tokyo, 181-8612, Japan［Received May 1, 2019：Accepted April 15, 2019］

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μm (“PS40”) and 20 μm (“PS20”) to study how differ-of the ALFs and Probe2 (Out) placed 10 cm after theent bubble sizes affect the capacity of the ALF in

ALFs. The bubbles were generated for 20 seconds,

terms of GME removal.

from 10 seconds after the measurement was started.
Three measurements were taken for each of the set-

Ⅱ．Study methods

tings.
2．Date analysis

1．Measurement methods
A hard-shell venous reservoir (CAPIOX-RR-40：Teru-

The bubble count and volume removal rates (％)mo), an artificial lung (CAPIOX-FX25：Terumo), andwere calculated based on the bubble count and vol-a centrifugal pump (CAPIOX：Terumo) were used forume measured with Probe1 ( In) and Probe2 (OUT) of

the experimental circuit design. Multiple pre-bypass

the BC100, respectively. The mean bubble size mea-

filters ( PP3802：Pall) with a filter pore size of 0.2 μm

sured before and after passing through the ALF andwere lined up before the bubble generator to preventthe bubble size shrinkage rate (％) from before to

bubbles from recirculating in the circuit. The experi-

after passing through the ALF were determinedmental circuit was filled with an aqueous solution ofusing the following formulas：glycerol (2.35 cP, 37℃). The centrifugal pump was set

Mean bubble size＝

to a flow rate of 4 L/min, and the internal circuit pressure, to 200 mmHg (Fig.1).

ΣN i×D i
ΣN i

Ni＝number of bubbles

The bubbles flowing into each of the ALFs were mi-

Di＝respective bubble size
(MBS1－MBS2)
Bubble shrinkage rate (％)＝
×100
MBS1

crobubbles generated by the electrolytic bubble method, in which a perfusion solution is electrolyzed to produce bubbles 7 ). Groups of bubbles with a mean bubble



MBS1＝probe1 (Mean Bubble Size)

size of 50, 100, or 180 μm were generated right beforeMBS2＝probe2 (Mean Bubble Size)entering the ALFs and were passed into the ALFs.

Statistical processing was performed with SPSS

The ALFs of both pore sizes had a fill volume of 100

Statistics ver21 ( IBM ), with the significance set tomL, maximum blood flow rate of 8 L/min, and mem-

P<0.05.

brane surface area of 550 cm 2 .

Ⅲ．Results

Bubbles before and after the ALF were counted

1．Measurement resultswith Bubble Counter BC100 (GAMPT). The measurement site was 30 cm from the bubble generation de-

Table 1 shows the bubble count, bubble size, andvice to the ALFs, with Probe1 (In) placed 10 cm ahead

bubble volume removal rates (％) calculated from the

Thermometer
Oxygenator

Bubble Counter
BC100
Reservoir
Pressure Meter

Arterial Line
FilterElectrolysis Bubble
Generator
Probe 1
10cm

Centrifugal Pump
Pre-Bypass Filter

Fig.1

120

Probe 230cm

Schematic layout of the experimental circuit

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10cm

Jpn J Extra-Corporeal Technology 46（2），2019

Table 1
Bubble
Pore
Size
Size
（μm） （μm）
40
20

50

Bubble Count

Measurement results according to bubbles size

Mean Bubble Size
（μm）
In
Out

Bubble Volume
（nL）
In
Out

Bubble Count
Bubble Size
Bubble Volume
Removal Rate Shrinkage Rate Removal Rate
（%）
（%）
（%）

In

Out

887.7

492.7

50.9

35.1

172.6

16.0

44.5

30.9

90.6

（84.2）（45.1）

（1.5）

（0.6）

（32.6）

（1.9）

（0.7）

（2.4）

（1.3）

968.3

425.0

51.9

29.3

231.5

7.0

56.1

43.6

97.0

（42.1）（20.2）

（0.6）

（0.6）

（17.9）

（0.6）

（0.6）

（0.4）

（0.1）

P-values

0.212

0.077

0.346

＜0.001

0.52

0.002

＜0.001

0.001

0.001

40

2675.32307.7

100.4

51.0

2720.5

239.3

13.7

49.2

91.2

（2.0）

（0.3）

（1.9）

（1.1）

（0.5）

96.8

41.2

9.9

57.5

94.7

（0.4）

（3.5）

（3.8）

（3.4）

（1.4）
0.017

（185.5） （113.0）
20

1002724.02454.3（44.2） （139.3）（190.5） （19.3）
2437.0129.1（105.6） （40.3）

P-values

0.681

0.23

0.037

0.008

0.087

0.013

0.205

0.016

40

3115.33332.7

182.0

87.6

16077.6

1812.8

−7.0

51.9

88.7

（18.2）（28.9）

（6.4）

（3.7）

（1.5）

（1.8）

（1.6）

20

180

P-values

3296.34262.3

181.6

67.7

（7.6）

（49.5）

（0.4）

（0.4）

＜0.001＜0.001

0.926

0.001

（934.4） （259.6）
1245.1

−29.3

62.7

92.5

（235.1） （15.1）

16578.5

（1.8）

（0.3）

（0.2）

＜0.001

0.001

0.419

0.019

0.014
Mean
（Standard deviation）

bubble count and bubble volume measured with
Probe1 ( In) and Probe2 (Out) when groups of bubbles

（％）
100
90

with a mean bubble size of 50, 100, and 180 μm were

80
70

passed into each of the ALFs.

＊

60

2．Bubble size shrinkage and bubble volume remov-

50

al rates＊＊

P＜0.05＊＊

P＜0.01■ PS40P＜0.01■ PS2040
30

The bubble size reduction for PS40 and PS20 in the20groups of bubbles according to size were as follows：

100

50 μm, 30.9±2.4％ and 43.6±0.4％ ( P<0.01)；100 μm,
49.2±1.1％ and 57.5±3.4％ ( P<0.05)；and 180 μm, 51.9

Fig.2

±1.8％ and 62.7±0.3％ ( P<0.01), respectively, with
PS20 having a significantly higher rate of bubble size
reduction from before to after the ALF for all bubble

（％）
100

sizes. The bubble volume reduction rates were as fol-

98

50μm

＊＊

＊

P＜0.0594

μm, 91.2±0.5％ and 94.7±1.4％ (P<0.05)；and 180 μm,

180μm

P＜0.0196

lows：50 μm, 90.6±1.3％ and 97.0±0.1％ ( P<0.01)；100

100μm

Bubble size shrinkage rate according to bubble size＊

92

P＜0.05■ PS409088.7±1.6％ and 92.5±0.2％ ( P<0.05), respectively, rep-

■ PS2088

resenting a significantly higher rate of bubble volume86

reduction for PS20 (Figs.2 and 3).

84
82

3．Bubble count removal rate

80

The bubble count removal rate in the group of 50
μm bubbles was 44.5±0.6％ for PS40 and 56.1±0.4％

Fig.3

50μm

100μm

180μm

Bubble volume removal rate according to bubble sizefor PS20, showing a significantly higher bubble countremoval rate for PS20 (P<0.001)；when the bubble size

－29.3±1.8％ for PS20, with both having an increased

was 100 μm, it was 13.7±1.9％ for PS40 and 9.9±3.8

bubble count at the exit site as compared with that at％ for PS20, indicating no significant difference ( P＝

the entrance. The results also showed that PS20 had

0.205). When the bubble size was 180 μm, the bubble

a significantly greater increase than PS40 ( P<0.001

count removal rate was －7.0±1.5％ for PS40 and；Fig.4).

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（％）
100

Surface tension : γ
Bubble internalpressure

80
60

＊＊＊

P＜0.00140■ PS400−20■ PS20

NS

20

＊＊＊

50μm

100μm

ΔP

P＜0.001

180μm

−40

Fig.4

Bubble count removal rate according to bubble size

Circuit pressure

Fig.5

Ⅳ．Discussion
1．Bubble count removal rate

‌Relationship between the circuit and bubble internalpressures

BPP＝In their report on GMEs at ≦100 μm, Jabur et al.

4・γ・cosθD………… (1)showed that an ALF with a pore size of 20 μm removed

γ：liquid surface tension

admixed emboli at a significantly greater rate than aθ：bubble contact angle,

40 μm filter (33.4％ vs 62.1％, P＝0.0029) 8). Riley et al.,D：pore size

who studied the capacity for bubble removal of 10 dif-

The relationship between the pressure inside and out-

ferent ALFs with pore sizes ranging from 20 to 43

side the bubbles is the sum of the internal pressure of

μm, showed that ALFs with a pore size of ≦27 μm

the circuit, as per Fig.5, and the internal pressure of

removed more GMEs 9). The present study also yield-

the bubbles according to the Laplace equation, thus

ed similar results where the group of 50 μm bubbles

yielding the formula (2).

passed through each of the ALFs (40 μm：44.5％ and20 μm：56.1％, P<0.001).
The bubble count reduction rate in the group of 100
μm bubbles was decreased in contrast to that in thegroup of 50 μm bubbles wherein more bubbles passed

Bubble internal pressure ( P)＝Circuit pressure＋

4×γ
BUbble diameter ………………………………………………………… (2)Pressure difference (ΔP )＝4×γ
BUbble diameter…… (3)

through the ALFs. The mean bubble size at the ALF

If the circuit has a constant internal pressure, the in-exit side was 51.0±0.3 μm for PS40 and 41.2±3.5 μm

ternal pressure P of the circuit is inversely propor-

for PS20, confirming the presence of bubbles larger

tional to the size of the bubbles, and the pressure in-than the pore sizes of the ALFs. This suggests thatside the bubbles increases. With the bubble size andbubbles may have been deformed while passing throughsurface tension, the pressure differential ΔP for in-

the pores of the filters. With the 180-μm bubbles, theside/outside the bubbles can be calculated using thefact that both PS40 and PS20 had an increased bub-formula (3).

ble count at the ALF exit site implies that bubbles

The pressure differential inside/outside the bubbles

may have burst inside and flowed out from the ALF.

that was calculated for each bubble size from the rep-

2．Bubble deformation and bursting

resentative values of the surface tension of the solu-

Normally, when a bubble is stuck onto a filter, it doestion ( Table 2) showed that the larger the bubbles, thenot pass through the filter if it is larger than the poresmaller the pressure differential inside/outside thesize. However, when the pressure outside the bubbles

bubbles ( Table 3). Bubbles with a diameter of 50 μm

exceeds the pressure inside the bubbles, the bubbles

had a pressure of 34.8 to 43.8 mmHg, higher than theare deformed, causing them to pass through the pores.

internal pressure of the circuit, but this decreased

The pressure at this time is called the bubble pointfrom 21.9 to 17.4 mmHg for 100 μm bubbles and frompressure ( BPP), which is represented by the following

12.2 to 9.7 mmHg for 180 μm bubbles, such that theformula (1)larger the bubbles, the smaller the pressure differ-

10).

ence between inside and outside the bubbles, and themore readily the spherical bubbles deform and pass122

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Jpn J Extra-Corporeal Technology 46（2），2019

Table 2

Surface tension of liquids

gest a decreased GME removal efficiency due to thedeformation and bursting of the bubbles.

Surface tension（mN/m）
Water（20℃）

73

Glycerin（20℃）

63

Blood（37℃）

58

The size of the bubbles flowing into the ALFs affects the venous reservoir filter size. Comparison offilter sizes of 100 to 105 μm and 40 μm for the venous reservoir has yielded results that showed that

Table 3Differences in pressure inside and outside

the GME removal rate was higher with a pore size of
40 μm for the venous reservoir 12). Groom et al. foundBubble diameter（μm）

Water

Glycerin

Blood

50

43.8

37.8

34.8

100

21.9

18.9

17.4

180

12.2

10.5

9.7

27 μm reduced the number of microemboli coming

250

8.8

7.6

7.0

from the arterial line of the CPB circuit by 85.7％,

350

6.3

5.4

5.0

from 596 to 80, and reduced the number of microem-（mmHg）

boli detected in the patient’s left and right middle ce-that changing the venous reservoir filter size from 105
μm to 30 μm and the ALF pore size from 40 μm torebral arteries by 66.1％, from 407 to 138 13). Thesethrough the pores. The results of the present study

reports and the results of the present study suggest

also show the possibility that some 100 μm bubbles

that to increase the GME removal rate of a CPB cir-were deformed while passing through the pores. Hav-

cuit, use of a venous reservoir with a small filter size,

ing an outside pressure that exceeded the internal

keeping all of the bubbles flowing into the ALF be-pressure of the bubbles may have caused the 180 μm

tween the sizes of 40 to ≦50 μm, and use of an ALF

bubbles to burst, which would explain the increased

with a pore size of 20 μm may be useful to prevent

bubble count on the ALF exit site.

the bubbles from deforming or bursting.

3．Bubble size and volume reduction rates

Ⅴ．Conclusion

The results for the bubble size shrinkage and bubble volume removal rates showed that PS20 had

According to the present study, the larger the bub-greater shrinking effect on the bubbles and reduced

bles, the lower the internal pressure inside the bub-the bubble volume. Microbubbles that flow into thebles, and thus, the more readily the bubbles deform or

ALFs have little buoyancy, and are thus, expected toburst while passing through the filter. Therefore, al-

not flow with the stream, and stick to the filter andthough the ALFs havea higher GME removal capacity

remain there. Fiore et al. anticipated that results fromfor bubbles with a size of 50 μm, bubbles with a size

simulation using a numerical model for the trajecto-of 100 μm deform and pass through the ALF pores.

ries of microbubbles would show that a significant

The 180 μm bubbles were also shown to burst, increas-

number of bubbles with a maximum size of 1,000 μm

ing the number of bubbles.

would be in contact with the filter

11). A pore size of

The authors declare that they have no COI.

20 μm would theoretically have a two-fold increase
from a 40-μm BPP, so PS20 would have a longer time

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