Sensors and Actuators A 331 (2021) 112904

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Sensors and Actuators A: Physical

journal homepage: www.elsevier.com/locate/sna

Detecting gastric occult blood: A wireless capsule system for

screening upper gastrointestinal cancer
Panpan Qiao a , Luo Yu a , Jingwen He a , Ailin Zhang d , Hongyig Liu a,b,∗ , Xitian Pi a,c,∗
a
Key Laboratory of Biorheological Science and Technology of Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR
China
b
Chongqing Engineering Research Center of Medical Electronics Technology, Chongqing 400030, PR China
c
Key Laboratories for National Defense Science and Technology of Innovative Micro-Nano Devices and System Technology, Chongqing University,
Chongqing 400030, PR China
d
Pharmaceutical Science College, Chongqing University, Chongqing 400030, PR China

a r t i c l e i n f o a b s t r a c t

Article history: Surgical treatment of early cancer has a good prognosis. Prior research reported that gastric occult blood
Received 30 December 2020 detection can be used to screen early upper gastrointestinal cancer. This paper proposes a gastric occult
Received in revised form 23 April 2021 blood detection (GOBD) capsule system to detect occult blood in gastric juice for screening upper gas-
Accepted 4 June 2021
trointestinal bleeding and tumor diseases based on colloidal gold immunochromatography. In-vitro and
Available online 8 June 2021
in-vivo experiments are conducted to testify the overall function of the system. Experiments show that all
occult blood test results are displayed on the external PC. Results demonstrate that the GOBD capsules in
Keywords:
our experiments can detect the occult blood, and send the occult blood information outside from normal
GOBD capsule system
Gastric juice occult blood
saline and animal bodies. This information is then received by external receiver and displayed on a PC.
In-vitro experiment © 2021 Elsevier B.V. All rights reserved.
In-vivo experiment

1. Introduction
Gastric cancer has a high morbidity and mortality. However, sur-
gical treatment of early gastric cancer has a good prognosis, and
the 5-year survival rate can reach more than 90 % [1–3]. There-
fore, early diagnosis and timely treatment of gastric cancer are
of great significance to reduce gastric cancer mortality. Clinically,
the method witch has the highest accuracy for diagnosing gas-
tric cancer is gastroscopy plus histopathological examination [4–6].
However, gastroscopy is not only painful for patients, but also car-
ries the risk of cross-infection [7]. Although painless gastroscopy is
another solution, it requires general anesthesia. Butdrug-related
side effects and increased cost limit its use in certain popula-
tions [8,9]. Therefore, it is necessary to conduct screening before
gastroscopy, especially for those who do not have upper gastroin-
testinal disease, but only undergo routine physical examination.
Early tumor cells (esophageal cancer, gastric cancer) are easy to
damage the mucosa and cause lesions [10,11], resulting in a very
Abbreviations: FOBT, fecal occult blood test; GOBD, gastric occult blood detec-
tion; GOB, gastric occult blood; OB, occult blood; NC, nitrocellulose; C area, control
area; T area, test area.
∗ Corresponding authors at: Chongqing University, Chongqing 400030, PR China.
E-mail addresses: liuhongying@cqu.edu.cn (H. Liu), pixitian@cqu.edu.cn (X. Pi).
small amount of blood (occult blood) [12] that cannot be observed
by the naked eye leaking into the gastric juice. The detection of
occult blood in gastric juice can be used to find upper gastrointesti-
nal bleeding and tumor diseases.
The traditional occult blood test method of gastric juice is to
extract the gastric juice through intubation or other methods, and
then to detect it in vitro by chemical or immunological methods
[13]. The method of extracting gastric juice is complicated and
needs to be carried out under the guidance of the doctor. More-
over, the intubation process will bring pain to the examinee, and
may also cause scraped bleeding of the esophagus and stomach
wall, thus affecting the test results. Qin,etl [14,15] proposed occult
blood beads. The subject needs to swallow a cotton ball with a
thread. The cotton ball absorbs gastric juice, and then it will be
pulled out of the throat to detect occult in vitro. In this process, the
subject will feel nausea, vomiting and other discomfort due to the
pulling of the thin line. Several magnetic-controlled capsules for the
stomach have been reported and showed promising applications
[16,17]. However, these capsules only mimic the role of an intuba-
tion gastroscopy, which takes images of the stomach wall and does
not detect occult blood in the stomach fluid. Fecal occult blood test
(FOBT) is used to detect occult blood in human feces [18,19]. The
bleeding site may be esophagus, stomach, small intestine and colon.
The specific lesion site cannot be determined.

https://doi.org/10.1016/j.sna.2021.112904
0924-4247/© 2021 Elsevier B.V. All rights reserved.
P. Qiao, L. Yu, J. He et al.
We propose a gastric occult blood detection (GOBD) capsule
system. The capsule is taken orally into the stomach, immersed
in gastric juice, detects the occult blood information in the gastric
juice, and transmits the detection results to an outside computer.
The device has applied for and disclosed national invention patent
[20]. We conduct in vitro and in vivo experiments to verify that the
capsule can detect occult blood and transmit the test information
to the outside of the body and display it on the computer.
2. Material and method
2.1. Structure of capsule system
The structure of GOBD capsule system, shown in Fig. 1, includes
GOBD capsule and external device. The GOBD capsule contains
GOB detection unit, image acquisition module, wireless transmit-
ter, reed switch and button batteries. External device contains a
receiver, signal converter and PC. GOB detection unit is used to
detect occult blood. The occult blood information is acquired by
image acquisition module and transmitted outside. After the out-
side receiver obtained the occult blood information, the final occult
blood detection result is displayed on the PC through the signal
converter.
2.2. GOBD capsule
2.2.1. GOB detection unit
The GOB detection unit is an important component that directly
contacts the gastric juice and performs occult blood detection. Since
the capsule system is used for the detection process in the human
stomach, it should have a unique structure to meet the environ-
mental requirements. We design the structural scheme by carefully
considering the physiological structure of the human stomach and
the composition of gastric juice, as shown in Fig. 2(a).
GOB detection unit is cylindrical, including holes, absorbent
material, OB (Occult blood) test strip and strip carrier. There are
six holes, round and symmetrically distributed at the front end of
the capsule to facilitate the flow of gastric juice into the capsule.
In order to avoid the saliva and water in the mouth entering into
the capsule, a layer of edible gelatin is used to cover the holes.
The edible gelatin can dissolve in the gastric juice within 2 min,
exposing the holes to the gastric juice. The absorbent material is
German-made collodion, which absorbs gastric juice while filter-
ing the viscous material in the gastric juice. The collodion prevents
the viscous material from blocking the cellulose membrane molec-
ular sieve of OB test strip made by the principle of colloidal gold
immunity, avoids resulting in false negatives. The pH value has an
impact on the stability of colloidal gold and the labeled protein.
Some experimental studies have shown that when the pH value is
5∼7, the positive rate of the test result is the highest. While the pH
value of normal gastric juice is less than 3.0 [21], the test result is
prone to false negative. To neutralize the influence of pH value of
gastric juice, it is necessary to keep the pH value of gastric at 5∼7.
So, we aerosolized an appropriate amount of Al (OH)3 powder on
the absorbent material. Strip carrier is a very thin silicone sheet
that servers as a carrier for OB test strip while isolating the gas-
tric juice and the electronic components inside the capsule. OB test
strip is prepared by colloidal gold immunochromatography, includ-
ing sample pad, colloidal gold labeled antibody pad, nitrocellulose
(NC) membrane and absorbent pad. The NC membrane has two
areas covered with antibodies: control area (C area) and test area
(T area). When test sample is dropped on the sample pad, with cap-
illary action, the sample fluid moves forward to the colloidal gold
labeled antibody pad, soaked the colloidal gold pad and dissolved
the gold labeled antibody. If the antigen to be tested is present in
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Sensors and Actuators A 331 (2021) 112904
the sample, the combination of the antigen and the gold-labeled
antibody continues to move upward with the liquid. When passing
through T area and C area, the antigen-antibody complex will be
captured by the antibodies coated in the two areas, forming two
red regions, which is a positive result. If there is no antigen to be
tested in the sample, the gold-labeled antibody will move upward
with the liquid and be captured when passing through C area, but
will not be captured when passing through T area, making only
C area turn red, which is a negative result. Absorbent pad absorbs
excess water and makes capillary force stronger. Three possible test
results are shown in Fig. 2(b), positive: both C and T area turn red;
negative: C area turns red, while T area has no color change. Invalid:
no color changes in C area, T area turns red, or no color changes in
either C area or T area.
2.2.2. Image acquisition module
The image acquisition module is required to be small dimen-
sions. Here we applied imaging sensor OV6922 (Omni Vision
Company, USA), size of chip 2.1 mm × 2.3 mm, resolution 320 × 240
(NTSC standard), sampling rate 60 frames per second. The module
has two green LED lights to provide the lighting environment.
2.2.3. Wireless transmitter
RTC6701 (Rich Wave, Taiwan) is used to design wireless trans-
mitter. RTC 6701 is a frequency modulation (FM)/frequency-shift
keying (FSK) transmitter intended for application on 2.4 GHz
industrial scientific medical (ISM) band analog FM or digital FSK
transmission. Its driving voltage is 3.1V∼3.5 V and 2∼3 button bat-
teries can meet the requirement.
2.2.4. Reed switch
There are two types of reed switch: normally open and normally
closed. The reed switch in GOBD capsule is normally closed. When
storing the capsule, it is positioned close to magnet with a specific
magnetic field direction. When the capsule is not in use, the reed
switch disconnects due to the effective magnetic field; when in
use, taking the magnet far away from the capsule, the reed switch
returns to on state, and the capsule will start to work.
2.2.5. Packaged capsule
Fig. 3 shows the 3D drawing of GOBD capsule and its assembled
prototype with size of 53 mm*␸14 mm. The size of image acqui-
sition module is 14*5 mm, and the size of wireless transmitter is
12mm*6 mm.
2.3. External device
RF chip RTC6711(Rich Wave, Taiwan) is utilized in the receiver
to cooperate with RTC6701. RTC6711 is intended for application
on 2.4 GHz band analog FM or FSK demodulation. The video signal
obtained by external receiver is an analog signal. We use signal
converter EASY CAPTURE to convert the NTSC analog video signal
into a digital signal, and then connect to a PC to display it.
3. Experiments and results
3.1. Performance test of reed switch
The reed switch is the main switch inside the capsule. The type
of reed switch used in this study is normally closed. In order to keep
the capsule in a power-off state when it is not working, the capsule
needs to be stored in an effective magnetic field. When the capsule
is away from the magnetic field, the reed switch is closed and the
capsule starts to work.
We prepare three capsule prototypes and use permanent mag-
nets to generate magnetic field. When the magnets are close to and
P. Qiao, L. Yu, J. He et al. Sensors and Actuators A 331 (2021) 112904

Fig. 1. Functional block diagram of GOBD system.

Fig. 2. (a) Structural scheme of GOB detection unit. (b) three possible test results: positive, negative, invalid. (For interpretation of the references to colour in this figure text,
the reader is referred to the web version of this article).

Table 1 body in real time. At 3.3 V operating voltage, the working current
Status of LED lights when the magnets were close to and away from capsule.
of image acquisition module is about 19 mA, and wireless transmit-
Capsule prototype Status of the LED lights Status of the LED lights when ter is about 12 mA. The total working current of the GOBD capsule
when the magnet is close the magnet is away from the is about 31 mA.
to capsule capsule

1 Not lit Lit

2 Not lit Lit
3 Not lit Lit
far from capsule prototypes, we observe and record the status of the
LED lights inside the capsule. Fig. 4 shows the experimental process.
Results (in Table 1) show that when the magnets are close to the
capsule prototypes, the LED lights in the three capsules are not lit,
indicating the capsules are in a power-off mode. When the magnets
are away from the capsule prototypes, the LED lights are lit, indi-
cating the capsules are in working mode. The result demonstrates
that the reed switch used in the experiment works properly.
3.2. Capsule power consumption
When the GOBD capsule starts working, image acquisition
module and wireless transmitter start to work. Image acquisition
module acquires images at a frame rate of 60 frames per second,
and the wireless transmitter sends the images to the outside of
3.3. GOB detection unit experiment
OB test strip has a detection range for hemoglobin concentra-
tion. If the hemoglobin concentration is too low, T area of OB test
strip will not change color, and hemoglobin will not be detected;
if the hemoglobin concentration is too high, T area of OB test strip
will also not change color due to “post-zone phenomenon” (anti-
gen excess) [22]. Previous studies have shown that the detection
range of hemoglobin concentration of the GOB detection unit is
6∼1800 ␮g/mL [23]. One question here is that, what is the relation-
ship between the hemoglobin concentration and the color intensity
of the OB test strip on the GOB detection unit? We design the
following experiment to find their relationship. The experiment
is conducted to the GOB detection unit. Normal human blood is
from a consenting adult female, with hemoglobin concentration of
139 g/L. Protocols of this study is approved by Ethics Committee of
Chongqing University Cancer Hospital and the volunteer signed the
informed consent after being explained the procedure of the study
in detail. Simulated gastric juice (sodium chloride 2.0 g, pepsin

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P. Qiao, L. Yu, J. He et al. Sensors and Actuators A 331 (2021) 112904

Fig. 3. (a) 3D view of the GOBD capsule. (b) prototype of GOBD capsule. (c) image acquisition module. (d) wireless transmitter.

Fig. 4. Experimental process. (a) the magnet is close to capsule prototype. (b) the magnet is away from capsule prototype.

3.2 g, hydrochloric acid 7 mL) is prepared [24,25]. The Hb con- the grey value of T area changes from high to low and then back
centrations of test samples are prepared with different settings: to high (the lower the grey value, the darker the color). When the
6 ␮g/mL, 10 ␮g/mL, 20 ␮g/mL, 50 ␮g/mL, 200 ␮g/mL, 800 ␮g/mL, hemoglobin concentration is 20 ␮g/mL, the color of T area on OB
1200 ␮g/mL, and 1600 ␮g/mL. Each concentration is tested 5 times. test strip is deepest and the grey value is the lowest.
Only six holes are immersed in the liquid with fixture holding the
GOB detection unit. The detection processes are recorded and the
3.4. In-vitro experiment of GOBD capsule
grey values of T area on OB test strip are calculated.
Fig. 5 is the OB test strip after detection of different hemoglobin
3.4.1. Experiment in the condition of air
solutions and Fig. 6 shows the grey values of T area on OB test strip
The experiment is conducted to verify the overall function of
with different hemoglobin concentrations in line chart. With the
the GOBD capsule prototype, that is, whether it can correctly detect
increase of hemoglobin concentration, the reaction color of C area
occult blood information and send the information outside the body
and T area changes from light to dark and then back to light, and
in an air environment. 20 ␮g/mL hemoglobin solution is prepared

4
P. Qiao, L. Yu, J. He et al.
Fig. 5. OB test strip after detection of different hemoglobin solutions.
Fig. 6. Grey values of T area on OB test strip with different hemoglobin concentra-
tion.
Fig. 7. Photo of OB test strip after the test.
by using human blood and simulated gastric juice, and placed in a
beaker. We test three prototypes, which are clamped by a clamp
and immersed holes of capsules in the hemoglobin solution. Other
electronic circuits in the capsules are not soaked, allowing the wire-
less signals to travel in the air. The external device is placed 1
m away from the prototype to receive signals and display image
information.
Fig. 7 is the photo of OB test strip after the experiment. The
results show that the color changes of C area and T area on the
OB test strip can be seen on PC during the occult blood detection
process of the three prototypes, indicating that the entire capsule
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Sensors and Actuators A 331 (2021) 112904
system could work properly in the air environment. Our system can
not only detect the occult blood information, but also receive and
display the image outside the body.
3.4.2. Experiment in the normal saline
The above experiment has proved that the developed capsule
can detect occult blood information and transmit the signal in the
air. However, radio frequency signals will be attenuated when trav-
elling through human body. In this experiment, we will verify that
our capsule system can still send occult blood information to the
outside of the body in the artificially configured saline that sim-
ulates the environment of human body. There is no hemoglobin
and artificial gastric juice in the saline (easy to recover the capsule
prototypes). OB test strip in GOB detection unit adopts test papers
that have already been used with color rendering of T area and C
area. The configured normal saline (0.9 % sodium chloride aqueous
solution) [26] is filled in a 50*24*25 cm transparent water tank. We
put the capsule prototypes (n = 3) into the water tank and place the
external device outside the water tank to receive and display sig-
nals, shown in Fig. 8. In Fig. 8, we can see that the two-color areas
on the OB test strip from PC, indicating that the capsule system can
send occult blood information outside the normal saline, and the
information can be received and displayed on PC.
3.5. In-vivo experiment of GOBD capsule
The purpose of this experiment is to verify whether the capsule
can detect the occult blood in an animal body, and send the occult
blood information outside to be received and displayed. All proce-
dures are conducted in accordance with the protocols approved by
the Laboratory Animal Welfare and Ethics Committee of the Third
Military Medical University. The test objects are three live Bama
Miniature pigs weighing approximately 46−51 kg. Before the trail,
the animals were fasted for 24 h, then were anesthetized by intra-
venous injection and the limbs were fixed with ropes. In the fasted
state, the gastric juice volume of a 50 kg pig is 162.20 ± 8.39 mL [27].
We prepare 160 mL hemoglobin solutions with a concentration of
40 ␮g/mL in beakers. A gastric tube is inserted into the stomach
through the pig’s mouth and esophagus (Fig. 9a). The hemoglobin
solution in the beaker flows into the pig’s stomach through the gas-
tric tube. The volume of liquid in the pig’s stomach is about 320 mL,
and the hemoglobin concentration is about 20 ␮g/mL, which is the
concentration with the deepest color reaction of the OB test strip.
After that, we take out the gastric tube, attach GOBD capsule at
the end of the tube, and then insert the tube into the pig’s stom-
ach again. An iron wire enters the hollow gastric tube, pokes the
capsule off (Fig. 9b). Each Bama Miniature pig is assigned with one
capsule prototype. The external device is placed outside the animal
body (about 1 m away from the animal body) to receive and display
signals. Capsule prototype is followed with x-rays.
In Fig. 9c, we can see that the reaction process of OB test strip
in the capsule on PC, indicating that the capsules have detected
P. Qiao, L. Yu, J. He et al. Sensors and Actuators A 331 (2021) 112904

Fig. 8. Experiment in the normal saline.

Fig. 9. In-vivo experiment. (a) The hemoglobin solution in the beaker flows into the pig’s stomach through the gastric tube. (b) GOBD capsule is introduced into the pig’s
stomach. (c) photos of experimental process. (d) X-ray photo of the capsule prototype in the pig’s stomach.

6
P. Qiao, L. Yu, J. He et al.
gastric occult blood in the animal body, and successfully sent the
occult blood information outside the body. Fig. 9d is an X-ray photo
of the capsule prototype in the pig’s stomach.
4. Discussion
Chemical method and immune method are commonly used
to detect occult blood [28]. Chemical method is easily interfered
by animal blood, drugs and some vegetables, with poor speci-
ficity and low sensitivity. Immune method can specifically detect
human hemoglobin without interference from food and other fac-
tors, and it is non-toxic and harmless to human body. Meanwhile,
the sensitivity and specificity of immune method are superior to
chemical methods [29,30]. Therefore, this paper uses the colloidal
gold immunochromatography principle to design the GOB detec-
tion unit.
When there is mouth, esophagus or stomach bleeding, the blood
will flow into the gastric. Therefore, the detection of occult blood
in gastric is not only an early screening for gastric cancer, but also
an early screening for cancer of upper gastrointestinal tract.
Since the circuit board of the image acquisition module and
wireless transmitter are rectangular and a bit large, when build-
ing the GOBD capsule prototype, the long side of the rectangular
circuit board can only be parallel to the central axis of the capsule
cylinder, which makes the lens center point of the image acquisi-
tion module deviate from the central axis, resulting in the acquired
OB test paper images not in the center of the field of view, but this
does not affect the function of the entire capsule system. Although
the design of rectangular circuit board does not affect the function
of the capsule prototype, it is undeniable that this design makes
the capsule too large. Therefore, in future studies, we will continue
to optimize the design of the circuit inside the capsule, strive to
design a circular circuit board and reduce the size of the capsule.
The overall power consumption of GOBD capsule is about 31 mA.
Although it is very large, the capsule can complete the detection
process within half an hour, and the power of the alkaline button
batteries is sufficient.
In our in-vitro and in-vivo experiments, considering that the cap-
sule detection time is relatively short, there is no need to place the
test object far from the external device in practical application. The
external device is placed about 1 m away from the capsule in the
experiments.
The color reaction on the OB test strip is red, while the green
and red colors are complementary [31,32]. When the complemen-
tary colors are juxtaposed, they will cause a strong contrast of
color perception, making the red is redder and the green is greener.
Therefore, the light source in the capsule adopts green LEDs.
5. Conclusion
In this study a gastric occult blood detection capsule system
is proposed and developed to detect gastric occult blood. In-vitro
and in-vivo experiment of GOBD capsule indicate that the sys-
tem can work properly in the condition of air, normal saline, and
animals bodies, and transmit signals to the outside. These signals
then can be received and displayed on a PC. We also have iden-
tified directions for future research: minimize capsule size and
power consumption, semi-quantitative detection of occult blood.
With advantages of non-invasiveness and easy operation, this new
device system provides a novel method for early cancer screening
of upper digestive tract. With the deepening of follow-up research
and development of technology, the proposed system is promising
to be applied on the clinical applications.
7
Sensors and Actuators A 331 (2021) 112904
Author statement
Panpan Qiao: Methodology, Investigation, Writing - Original
Draft, Visualization
Luo Yu: Formal analysis, Validation
Jingwen He: Data Curation
Ailin Zhang: Software, Validation
Hongying Liu: Resources, Writing - Review & Editing, Funding
acquisition
Xitian Pi: Conceptualization, Supervision, Project administra-
tion
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgments
The authors thank Dengke Wang and Liudi Luo for help with the
in vivo porcine work. The authors also thank Chongqing University
Cancer Hospital and the Third Military Medical University for pro-
viding experimental materials. This study is funded by the National
Natural Science Foundation of China (Grant Number 81671850).
Appendix A. Supplementary data
Supplementary material related to this article can be found,
in the online version, at doi:https://doi.org/10.1016/j.sna.2021.
112904.
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Biographies
Panpan Qiao is a PhD candidate of Biological Engineering College of Chongqing
University now. Her doctoral research is “Gastrointestinal diagnosis microsystem”.
Luo Yu is a PhD a PhD candidate of Biological Engineering College of Chongqing
University now.
Jingwen He is an undergraduate student of Biological Engineering College of
Chongqing University now.
Ailin Zhang is an undergraduate student of Pharmaceutical Science College of
Chongqing University now.
Hongying Liu is an associate professor of Biological Engineering College of
Chongqing University and a master tutor. From December 2008 to December 2009,
she accessed to learning in Vanderbilt University (USA). She received her PhD in
biomedical engineering from Biological Engineering College of Chongqing Univer-
sity, in 2010. Her major research areas are the Research of Regional Drug Absorption
based on RCC and Smart Pill & Lab in a Chip.
Xitian Pi is a professor in Biological Engineering College of Chongqing University. He
did postdoctoral research work at new micro-nano device and system Defense Key
Laboratory of Chognqing University in 2007−2010. He received his PhD in biomed-
ical engineering from Biological Engineering College of Chongqing University, in
2004. His current research primarily focuses on Biological micro-mechanical elec-
tronic systems (BioMEMS), lab on a chip as well as terminal and personal health
information management system.