Proposed Implementation

intro

To implement our project in the real world, we covered various aspects of our project while following a typical product development process; creation of MVP and Beta product, considering primary users, and prospecting product release.

MVP(minimum viable product)

We will start this page with envisioning the MVP(minimum viable product) version of Thermopatch.

Design:

The basic functional components of thermopatch include the adhesive component and the capsule component. The capsule component is further divided into a wet capsule and a dry capsule. The wet capsule includes the ‘wet’ components including the buffer while the dry capsule includes the RNAs. To activate Thermopatch, the contents of the wet capsule has to be released by popping it. This can be simply done by applying pressure on the capsule component. Our preliminary design is shown below.

Function:

To estimate the RNA concentration required for our system to function, we conducted dry lab experiments. According to the results, we estimate that the concentration of each substance as it is shown below would be enough for our system to function. The details of our modeling results are shown in the results section

Name	Molar concentration (M)
H1	\( 4.08 \times 10^{-06} \)
H2	\( 4.08 \times 10^{-06} \)
Cs	\( 4.08 \times 10^{-09} \)
DFHBI-1T	\( 8.15 \times 10^{-05} \)

In order to test the intensity of light emission of our stickers, we modeled our RNA system according to our design. The results show that we can achieve the brightness of a full moon

For detailed results of our modeling, go to the contribution section

Our dry lab activities provided us the confidence to proceed our project.

Beta Product

In this section, we take it a step further and consider whether Thermopatches could be produced as a tangible product. Here, we list the relevant technologies that could enable the fabrication of each component of Thermopatch.

Dry capsule:

The first challenge that has to be dealt is packaging RNA in a form that can be stored for a long period of time. We didn’t want Thermopatches to require specialized storage conditions such as deep freezers or liquid nitrogen tanks. Moreover, the transition of RNA from the dormant form to the active form should be quick. We believe that our desired functionality can be achieved by adopting ‘RNA stable technology’ developed by Biomatrica (1)(2). This technology uses a shrink-wrapping method to create a thermostable barrier. With the protection provided by the barrier, RNAs can be stored up to 3.5 years at room temperature in wells that can accommodate up to 100ug. Activation is simply done by rehydration and does not require any purification processes such as multiple washing steps that may result in loss of RNA.

Wet capsule:

The main content of the wet capsule is the tris buffer. Tris buffer is recommended to be stored at room temperature to prevent the change in pH (3). No special storing condition is required. Therefore, the wet capsule and the dry capsule both can be stored at room temperature.

Adhesive component:

There may be concerns regarding skin compatibility of the adhesive component. However, we are confident that by utilizing the already extensively researched and tested band aid adhesives, we will be able to make the adhesive component skin compatible and minimize irritation. We can construct the adhesive component with High-density urethane non-woven fabric and acrylic adhesive as it is in commercial bandages.

Primary Users

We gained confidence, at least theoretically, that Thermopatches could be produced in a tangible form as shown in the previous sections. Then we wanted to consider specifically by whom and how our product is going to be used. We first specified the context in which our stickers could be effective and evaluated the benefits that could be brought by Thermopatch. As a result, we created a user guideline and a safety notice for the users.

User benefits

Thermopatch was initially devised for use on campuses in response to the current pandemic. We wanted to improve the current monitoring process which is costly and vulnerable. Our detailed ideation processes are shown in the engineering success section.

We believe two end-users can benefit from our stickers: the university and the students.

The university can reduce their expenses currently being spent on monitoring procedures. The current temperature screening methods involving contactless thermometers and infrared cameras need substantial expenses since they require human resources. On the other hand, our monitoring policy for ‘Thermopatch’ only involves students so it will drastically cut HR expenses. Therefore, we expect ‘Thermopatchs’ to be a lot cheaper than employing staff to operate conventional monitoring procedures involving contactless thermometers and infrared cameras.

Students benefit from our stickers since they can spot and take necessary actions if anyone in the rooms is experiencing fever. Their safety is reassured from the fact that ‘Thermopatch’ can continuously monitor temperature.

In Korea, there have been incidents of people using antipyretics to dissimulate fever to hide their symptoms(link). ‘Thermopatch’ will be able to sort those people out since it can monitor body temperature for longer periods of time. If someone sneaks in using antipyretics, the medication will eventually wear off and his/her body temperature will start rising up again. Thus, students have an extra line of defense for their safety.

User scenario

We came up with a recommended user scenario that can be used with Thermopatch. This policy enables continuous monitoring throughout the time spent inside the building. Also, we incorporated a self monitoring policy so that no additional staff is required for monitoring.

1. Receive Thermopatches upon entry.

2. Release fluid components by pressing and popping the internal capsule.

3. Remove the film on the back of the sticker and apply it on your neck over the carotid artery.

4. If you notice glowing in one of your peer’s stickers, please inform them.

5. When you are informed by your peers that the sticker is lit, leave the building and ask for more accurate measurement of your body temperature.

6. Remove the sticker at the exit and dispose it into the designated bin.

*Why on the neck?

Thermopatches have to be attached on a site that accurately represents the user’s body temperature and should be visible by others. Also, the site of attachment has to be user-friendly as much as possible. Regarding these conditions, the neck is the optimal site of attachment.

The neck is a relatively exposed site and the carotid artery, which is located in the neck, makes the neck the putative site of accurate body temperature measurement (4)(5). Moreover, applying the sticker on the neck is advantageous regarding user-friendliness. If the sticker is applied on a body part that can be seen by oneself, e.g. on the wrist, students will be constantly reminded of the presence of the sticker and would fear the lighting up of the sticker. To compromise this issue, we recommend our stickers to be applied where it can stay out of sight of the user so that the user is less reminded of its presence. We believe keeping the sticker out of sight of the user, but keeping it visible to others, would be more user-friendly.

Therefore, we strongly encourage the application of our sticker on the neck above the carotid artery since it can achieve high accuracy and cannot be seen by the user.

Safety guidelines

In the Safety section under the project tab, we have documented the safety considerations about Thermopatch. We compiled the safety guidelines for each component contained in Thermopatch. Here we focus on the user and present an overall safety guideline which the user should keep in mind.

1. Do not damage the capsule component and detach your sticker if the contents leak.

2. If the liquid gets on your skin, rinse with water.

3. After usage, stickers should be disposed in designated bins to minimize environmental harm.

Product release

In this last step, we evaluate the competitiveness of Thermopatch and consider a situation in which our stickers are released. Is our product going to bring economic benefits? Can Thermopatch be produced in large numbers? If it was actually released as a product, what are some laws that it may be subject to?

Economic benefit

To answer the first question, We focused on how the long-term monitoring enabled by Thermopatches can help close the loophole of the current monitoring system. In korea, there was a case in which antipyretics were used to circumvent the monitoring system at airports. According to a news article, a student who returned to South Korea from the U.S. in April 2020 evaded quarantine inspections by taking 20 pills of antipyretics (6). This can make it difficult to identify and keep track of the transmissions COVID-19, which could be especially threatening for high-risk groups of our society.

Another news article estimates that the total costs (epidemiological research costs, data management costs, etc.) caused by a single COVID patient would be 349,040 dollars, under the assumption that the patient infects 21 people four days later and those 21 people infects 3.5 people later on (7).

This incident proves that the detection by the current monitoring process can be easily evaded by the use of antipyretics. The vulnerability of the current system can be improved by the use of our stickers. Since Thermopatch monitors body temperature for a long time, the temporary reduction of body temperature by the use of antipyretics cannot evade the monitoring system of Thermopatch. Therefore, we prospect that the use of our products will be able to substantially reduce the costs generated by losing track of patients.

Mass production

Then, can we produce thermosensing RNAs in sufficient amounts for mass production? To provide an answer for this, we looked for already existing technologies that suit our purpose. Recombinant RNA technology seems to be a promising solution.

Recombinant RNA technology is used for constitutive production of large amounts of recombinant RNA using a tRNA-scaffold approach. For this method, RNA can cost-efficiently be obtained in multi-milligram quantities(7.5~15mg/L) without in vitro enzymatic manipulation (8). Since a single Thermopatch contains only <그람수 >g of RNA, this production scale is sufficient.

Relevant legislations

All medical-use products fall into one of the four categories(explained below) and registration is required. We wanted to know which category Thermopatch belongs to and the registration process it would have to go through if it were to be released as a product.

Definition of ‘Medical Appliance’ is an instrument or similar product used alone or in combination for used in humans or animals under any of the following:

1. Products used for the purpose of diagnosis, treatment, prevention or mitigation of disease. (Thermopatch)

2. Products used for the purpose of diagnosis, treatment, mitigation, or correction of injury or disability.

Products used for the purpose of inspecting, replacing, or transforming structures or functions

Among these categories, Thermopatch belongs to external diagnostic medical appliances. (Regulations on Medical Device Permission, Reporting, Examination, etc. (Article 2, Notice 13 of the Food and Drug Administration))

Class	Classification criteria for medical appliances	Classification criteria for external diagnostic medical appliances
1st class	Medical appliances with negligible potential risk	Little potential risk to individual and public health
2nd class	Medical appliances with low potential risk	Moderate potential risk to individual and low potential risk to public health
3rd class	Medical appliances with moderate potential risk	High potential risk to individual and moderate potential risk to public health
4th class	Medical appliances with the high risk	High risk to individual and public health

To be categorized as 1st class medical appliances, a manufacturing report is required. Reporting procedure of 1st class medical appliances is as follows

1. Online registration / application (Online civil application window for medical appliances)

2. Acceptance of report(Medical Device Information & Technology Assistance Center)

3. Receive registration document

From envisioning a minimum viable product to imagining actual production of Thermopatch, we considered various aspects that are necessary for the implementation of this product. We listed the relevant technologies and created guidelines that go with Thermopatch.Through this activity, we gained a clearer concept on the design and the usage of Thermopatch

References:

(1) https://www.labmanager.com/how-it-works/protecting-rna-samples-at-room-temperature-20965

(2) https://www.biomatrica.com/product/rnastable-ld/

(3) https://eng.bioneer.com/literatures/msds/MSDS_BufferTotal/C-9006_1M%20Tris-HCl(pH%208.0)_kr.pdf

(4) Imani, Farsad et al. “Skin Temperature Over the Carotid Artery, an Accurate Non-invasive Estimation of Near Core Temperature.” Anesthesiology and pain medicine vol. 6,1 e31046. 17 Jan. 2016, doi:10.5812/aapm.31046

(5) Selvaraj, et al., “Evaluation of skin temperature over carotid artery for temperature monitoring in comparison to nasopharyngeal temperature in adults under general anesthesia.” Anesthesia, essays and researches vol. 10,2 (2016): 291-6. doi:10.4103/0259-1162.172722

(6) https://www.donga.com/news/Society/article/all/20200405/100511077/1

(7) https://www.yna.co.kr/view/AKR20200518000600017

(8) Nelissen, F. H., Leunissen, E. H., van de Laar, L., Tessari, M., Heus, H. A., & Wijmenga, S. S. (2012). Fast production of homogeneous recombinant RNA—towards large-scale production of RNA. Nucleic acids research, 40(13), e102-e102.