Team:UCAS-China/Hardware

HARDWARE——cPLUS

What is cPLUS?

In order to assist in the treatment of thermosensitive bacteria, our hardware is designed to provide limited and stable heating at the lesion. "c" stands for "capsule", also for "℃". "PLUS" means our hardware shows higher function integration and stronger practicability.

Introduction:

We developed an innovative electronic capsule, cPlus, which can perfectly assist diagnosis and treatment of intestinal diseases. cPlus consists of a heating system, a sampling device, a clamping device, a positioning device and a remote-control system. With the accurate positioning(<1cm) and heating (<1000s to reach the target temperature within 1cm range) control, cPlus can be precisely located and heat the specific lesion to assist the targeted drug release from the engineered therapeutic bacteria. Not only for treatment, but cPlus contains a sampling device and can be combined with current imaging system for diagnosis. In the present research of intestinal flora, original technology of sampling from the feces is difficult to meet the requirements of sampling intestinal flora at specific location (including long-term fixed flora), cPlus fills a vacancy of intestinal flora accurate sampling. We believe cPlus will bring an evolution in the industry of medical microdevice.

Material:

Considering the small volume and high efficiency, we chose 50mm stepping motor, 5V40℃ PTC, stepping motor driver, remote conctrol receiver, rod sampler and some small electronic components to build up our model. While in our actual design, we will choose to use 5mm stepping motor and add CMOS and CCD in the capsule.

Design:

In order to demonstrate the interior design better, we made a model with most functions by using some ordinary materials.

Structure of cPLUS

Our capsule consists of 6 large parts, including heating system, sampling device, clamp device, positioning system, energy and remote control system.

Figure 1. Overview of our cPLUS

In the heating system, we used PTC thermostatic heating element as the heat source. Due to the limitation of its physical properties, the temperature of PTC heating element is constant under a certain voltage, which can well meet the requirements of constant temperature heating, safe and simple.

Figure 2. 5V50℃ PTC we use

Figure 3. PTC inside the capsule.

Our sampling device, which can take a sample at the lesion to analyze its physiological condition. When the heating temperature rises, the fuse breaks and the torsion spring drives the rod samplers to take samples.[5] In the model, we use hot melt adhesive to replace the fuse.

Figure 4. Our sampling device in the capsule

The clamping device, when the capsule reaches the designated lesion location, we can remote control the stepping motor to drive the manipulator to unfold and fix it in the intestinal tract to do the fixed work.[1]

Figure 5. The clamping device of the capsule.

Clamping device demonstration video

Our positioning system, we put a permanent magnet inside the capsule, and we measure its magnetic field through an array of magnetic sensors outside the body and figure out where the capsule is.[3]

Figure 6. The array of magnetic sensors outside the body.

Power supply system and remote control device. In the design, the battery adopts biocompatible battery and 2.4Ghz remote control module.

Figure 7. Our core component group in the capsule.

Figure 8. External remote control

The functioning process

The mechanism of our hardware is as follows.

1. After the capsule is ingested, it enters the body and travels through the digestive tract to the small intestine. In the process of its movement, it is located in real time by wearable magnetic field sensor array, and the path length of the electronic capsule is recorded.

Figure 9. The positioning process

2. When the magnetic induction device detected that the capsule has reached the designated position, the clamping system(mechanical arms) can be opened through a remote control device, and the capsule will be stuck. At the same time, the heating system, which is opened under remote control. Offering continuous heating and steady temperature, our capsule manages to cooperate with the microbial treatment of our project.

Figure 10. The heating and clamping process

3. While heating, the hot-melt adhesive melts due to the rising temperature, and then the torsion spring loses its binding, which will drive the ultra-elastic Nitinol wire to rotate, and three biopsy needles successively reach out of the capsule to collect intestinal tissues. [5]

Figure 11. The sampling process

4. After treatment, the external remote control device is used to stop the heating and retract the robotic arms. It is then allowed to creep along the digestive tract to the next heating point or out of the body. After that, the product will be processed.

Figure 12. Finish treatment

This is the general function and working process of our electronic capsule. With our design, the treatment using our portable capsule with high precision can be easily operated. Therefore, it’s possible for patients to complete the above operations at home. It not only achieves biosafety, but also guarantees high efficacy and convenience. We believe that our hardware can provide a promising tool for further relevent treatment.

Experiments

1. To select the most suitable PTC element for our capsule, we carried out heating experiments on pig’s small intestine using 2 different kinds of PTC elements.

● This is the first set of data that we measured

Figure 13. The PTC element is connected to a 6V voltage to heat the pig's small intestine at 5V 40℃

Data4: less than 1cm away from the heat source, it can reach over 40 ℃after 500s heating, and basically stable at 43-44 ℃ after 1500s

Data2:1-1.5cm away from the heat source, it can reach more than 40 ℃after 1500s, and basically stable

Data1&Data3: 1.5cm away from the heat source, heating to more than 40 ℃may take longer

● This is the second set of data that we measured

Figure 14. The PTC element is connected to a 6V voltage to heat the pig's small intestine at 5V 50℃

Data4: less than 1cm away from the heat source, the heating temperature continues to rise to more than 45℃ and will be higher, so it is not suitable

Data1 &2&3: 1.5cm away from the heat source, it may take longer to heat above 40 ℃

Of course, there are many other sets of test data, and here is just the conclusive data we found after comparing them

The conclusion was that we found the right PTC element and the right heating voltage to meet the requirements of our experiment -- that is, the PTC element was connected to the 6V voltage at 5V40℃

2. After building the positioning device, we did the following experiment to determine its location precision.

● We randomly selected 13 points for magnetic induction positioning test. According to a special location algorithm, we finally found that the average error was less than 1cm, which could well meet our requirements.[3]

Figure 15. The circle represents the position error and the possible range of the actual position

Expectations

There are some of the expectations that we have for hardware projects, what we want to achieve is that it's smaller, it's easier to operate, and patients can do it themselves.

Our anticipated design will also use a miniature CCD or CMOS camera to build an image transmission system that will allow our electronic capsules to work more accurately and efficiently, and to assist in the treatment of intestinal diseases by sending out images that will also function as colonoscopes. The 1.2mm miniature camera utilizes high quality components, including visual elements for the target and specially designed CMOS sensor technology. The tiny camera has a dedicated biocompatible component that opens a door to a new market for medical diagnosis and treatment.

Figure 16. Capsule with camera

The second is the use of new materials. In order to prevent capsule retention or adverse reaction between the manipulator and intestinal contact, we made our manipulator with natural biocompatible materials (chitin) from shrimp shells and crab shells, which could control the degradation time by adjusting the material proportion to meet our requirements.[4]

More intelligent operation, we expect to apply artificial intelligence technology in the design. After the input of the lesion coordinates, the computer will determine whether the lesion has been reached through the positioning system, image transmission and time, and then carry out the next instruction issuance and operation. The capsule condition can be monitored in real time during the whole treatment. After input coordinates, the whole process is operated by the computer, which is more simple and convenient, reduces labor input and reduces the incidence of failure.

The drug release device is to carry the bacteria and drugs we need to release at the lesion through the capsule cabin, release them at the right time, and control the diameter of the release hole to control the release rate.

Figure 17. Capsule with drug release device

The new sampling device is expected to be more powerful than the original one. In the design, stepper motor can be used to drive, more samples can be carried, and the sampling times of different sample points can be controlled for multiple sampling.

There are many parts that can be optimized and improved in our electronic capsule. We will continue to improve our capsule and try our best to make our product a medical device that can be operated easily by every patient.

Precautions for capsule use

One day before the inspection:

● The day before lunch into a light digestible diet, no water and food after 10PM

Smoking is prohibited for 24h.

● Strict bowel preparation requirements, otherwise it will affect the quality of the image and treatment.

Methods: take 20% mannitol 500ml electrolyte orally, and drink 1500ml to 3000ml.

On the day of inspection:

● Clothing should be loose, avoid tight clothes.

● Fix the sensor through a sticky pad on the tester's abdomen and hang it. The data recorder is connected to the waist belt.

● Take the electronic capsule with a small amount of warm water and move freely after taking it.

After swallowing the capsule:

● Do not eat or drink food or water for at least 2 hours after swallowing capsule. Water can be appropriate after 2 hours, and a small amount of liquid diet can be taken after 4 hours.

● Contact your doctor immediately if you experience any of the symptoms of abdominal pain, nausea or vomiting after taking the electronic capsule.

● Cannot be close to the strong electromagnetic source area, such as amateur radio transmitter, nuclear magnetic resonance, etc. Avoid contacting with other patients undergoing capsule to prevent interference of radio waves.

● Do not disconnect the check device or move the belt. Take care of the data recorder and avoid sudden movements or tapping it.

● Record any of the following conditions, such as eating, drinking or feeling abnormal, and return these records to the physician when you return the recording device.

● Avoid high-intensity activities that may cause sweating and do not bend during the examination.

After the inspection:

● The examination can be finished 8 hours after capsule endoscopy is swallowed, and the data meter and recorder can be removed and submitted to the doctor for data processing.

● Closely observe the stool, check whether the capsule is expelled, usually 8--72 hours. Magnetic resonance imaging is not allowed until the capsule has been proven to have been expelled from the body. X-ray is allowed.

● After the examination, the patient found the capsule after defecation, clean and return to the hospital.

Contraindications:

● Absolute contraindication is the absence of surgical conditions and refusal to accept any surgical procedures, suspected digestive tract stenosis or obstruction, perforation.

● Severe dyspraxia (untreated achalasia and gastroparesis)

● A patient who has a pacemaker or has implanted other electronic medical devices

● Have difficulty swallowing

●Pregnant women

Some answers to questions about capsule structure

Q: What if the capsule leaks?

First point: our whole shell and inner compartment are all made of medical polymer materials that will not be corroded by human digestive juices. IP protection level is up to IPX8, the highest waterproof standard, which can effectively prevent external digestive juices from entering the capsule and internal substances from spreading outward.

The second point: the reference waterproof cell phone technology, now our capsules inside the integrated circuit chips, circuit boards, motors and heating elements such as internal components adopt nano coating technology (EUBO coating), highest can reach IPX7 waterproof grade, can effective acid (intestinal pH6.8) at the same time, guarantee in some special cases, a small intestinal liquid into the internal circuit will not corrode the release of harmful substances.

Q: Are batteries safe in the body?

First, battery: we use the battery powered by an implanted device with high biocompatibility, which is low toxicity and harmless. In the worst case, it can prevent the battery's harmful substances from poisoning the intestinal tract or human body.[2]

Second, we have tried to use magnetic induction wireless power supply, but since our positioning part is based on magnetic sensor positioning, if the external magnetic field is used for power supply, it will affect our detection of capsule position.

Third, the surface of the battery is also made of EUBO waterproof nanomaterials to prevent corrosion of the liquid entering the capsule.

Q: Do capsules cause intestinal damage?

First, the shape of the whole capsule is very round, and there is no sharp Angle that can scratch the inner wall. Moreover, the tentacle surface of the manipulator designed by us has fine anti-slip lines. After extending the manipulator, pressure on the inner wall of the intestinal tract will prevent it from falling off. Mechanical arm use biodegradable medical polymer materials such as good compatibility, chitin), due to the degradation speed of biodegradable materials related to its physical and chemical properties (at the same time you need to determine the actual application environment of the physical and chemical properties), so we by controlling its molecular weight and component to control the degradation time, to the need of the degradation time, even if the capsule part structure of small probability of unpredictable situation happen, such as unable to remote control, motion structure of mechanical failure, damage to the battery, etc., will not be repaid for fixed parts of mechanical arm can also be degraded by human body in a short period of time and the rest will be drained out.

Moreover, as the mechanical arm is made of hard degradable material (degradable material is harmless to human body), it needs to replace the mechanical arm every time it is used. The capsule designed by us is fixed in the form of clasp. It is simple to disassemble and assemble, without affecting the portable use of the capsule.

The second point: the local effects of heating on human tissues are also being considered. The capsule will heat the lesion in the intestinal tract, similar to existing treatments such as deep heat therapy (heating center temperature is 40 to 43 degrees Celsius).The human intestinal temperature is about 37.8 degrees Celsius, containing a large number of enzymes and bacteria.

1. Through investigation, we found that in the environment of 40 to 45 degrees Celsius, these enzymes and bacteria will not be inactivated, but will affect their activity during the treatment time. However, the heating range of our capsules is within 1 to 1.5cm, and the range and its influence are small, so it will not cause irreversible damage.

2. Our hardware is due to adjuvant biotherapy, and most patients with colorectal cancer have chronic inflammation in the digestive tract environment. Our capsule shell refers to the shell of capsule enteroscopy, which has good biocompatibility, and local fixed point short-term contact will not aggravate intestinal inflammation.

3. If clinical and other studies find that prolonged heating will cause some adverse effects on the intestinal tract, we can choose intermittent heating to reduce the effect of heating on the intestinal tract.4. Heating itself is an effective routine treatment for cancer.

Third point: in rare patients, capsule retention is caused by unknown symptoms (small intestine tumor, Crohn's disease, etc.), which can be removed by ordinary endoscopic technology, and the previously undetected symptoms can be detected.

Q: Do the magnetic fields and radiation in your capsules affect you very much?

First point: as for the magnetic field, the magnetic field used for magnetic induction positioning is small in volume and the magnetic field intensity is not very big. It is much weaker than the magnetic field (electronic equipment, etc.) the human body is usually exposed to. Besides, the capsule has a short time in the human body.

The second point is about radiation. Limited to the capacity of carrying batteries, the system modules used in the capsules are all low-power, and the radiation is far less than that of electronic products such as mobile phones. The eventual design may include a tiny CMOS camera, but the power of its image transmission system is still small (see the image transmission and system setup for the capsule enteroscopy).

Q: Is it possible to reduce the capsule size?

1. The internal circuit will be designed as an integrated circuit chip. We deliver blueprints to almost any integrated circuit company to miniaturize the circuit. Existing integrated circuit chips also exist remote integrated chips and dedicated control chips.

2. The shell is made of biocompatible medical polymer material, and the mechanical arm is cut or cast with degradable material.[4] The size is determined according to the actual needs.

3. The motor adopts miniature stepping motor with length less than or equal to 5mm.

4. Batteries use high energy biocompatible batteries.[2]

Q: Is the sampling process safe?

1. Safety: We use the medical sampling rod after restructuring, the actual sampling structure and the medical sampling rod structure is consistent, safe and effective.

2. Sampling contamination: Two baffles will be embedded in a track on the inner wall of the capsule shell. When the sampling structure is rotated and finished, the rigid rod on the structure will move the first baffle, slide along the track, open the sampling port, and the sampling rod will extend the capsule for sampling. After sampling, the second hard rod will push the second baffle to close the sampling window. This will prevent contamination of the sampling chamber.

3. Save: After sampling, the sample stick will remain in the sampling chamber and the sample will be attached to the sample stick until the capsule is out of the body for recycling.

It is used in much the same way as enteroscopy, but cannot be used if the patient has perforated or ulcerated bowel at the lesion.

Q: How will the bacteria be delivered?

Our engineered bacteria will be released into the intestinal environment through enteric capsules in advance. The purpose of releasing the engineered bacteria without using electronic capsules is to make the distribution of engineered bacteria more even.

References

[1] CHEN Wen-wen. The Reshearch Of Micro Robot System For Gastrointestinal Diseases Diagnoses And Treatments Based On Wireless Power Transmission System[D] Shanghai Jiao Tong University,2013.

[2] Zhang, G., Geng, F., Zhao, T., Zhou, F., Zhang, N., Zhang, S., & Deng, C. (2018). Biocompatible Symmetric Na-Ion Microbatteries with Sphere-in-Network Heteronanomat Electrodes Realizing High Reliability and High Energy Density for Implantable Bioelectronics. ACS Applied Materials & Interfaces, 10(49), 42268-42278.

[3] Wu, X., Hou, W., Peng, C., Zheng, X., Fang, X., & He, J. (2008). Wearable magnetic locating and tracking system for MEMS medical capsule. Sensors and Actuators A: Physical, 141(2), 432-439.

[4] Juan Lu. Preparation and characterization of chitosan-based controlled-release material[D]. Southwest University. 2011

[5] ZHU Guo-xin. The research of a biopsy mechanism for capsule robot. Machinery Design and Manufacture. 2013(06):168-170.