Problem-analysis Groningen

Introduction

This page describes the analysis of the problem we are solving in the iGEM project. The method of this analysis is based on the design method taught in the Bachelor Life Science and Technology with the major Biomedical engineering at the University of Groningen. During the courses Designing Biomedical Products 1, 2 and 3 of the Bachelor, this is always the first step of the project when you want to design a product for a biomedical application. Part of the framework for the problem analysis is based on information from [1] since this document is also focused on developing a medical device for measuring a physiological signal. In this problem analysis first the problem is defined in the problem definition where the stakeholders and a cause-effect order diagram are given. Then the goals of the product are described which can be used for the description of the assignment we are finishing in this iGEM project. After this, a list of requirements for the biomedical product is given. The last part is the function analysis which describes in an abstract way all the functions the product should have to fulfill the goals of the assignment.

Problem definition

The stakeholders are the ones that have an influence in/or are influenced by the problem of biofilm infections in patients. The stakeholders should be considered because they are important for the product's success. The stakeholders' characteristics, expectations, potentials and deficiencies, and implications for the project can be found in Table 1. A different stakeholder analysis is performed in the Stakeholder analysis on the wiki page. The one performed here is more in-depth for certain stakeholders while the other one is more stakeholders but in a more general way.

Stakeholder	Characteristics	Expectations	Potentials and deficiencies	Implications for the project
Patient	Has an implant or will get one because of a not properly functioning body part Will wear the implant 24/7 Reluctant to proceed with major surgery for diagnostic purposes ^[2] Hesitant to use less invasive diagnostic techniques which are developed by researchers because they need further evaluation^[2] If the patient has a biofilm, it is difficult to treat through conventional means such as antibiotics One of the major causes of implant failure is infections at the site of implantation ^[3] Pain if there is infection Stress (does not know if they have an infection or not) Needs a new implant if the infection is too severe May not have enough money or does not want to spend money on a product	No infection If there is an infection, the patient wants to get rid of the infection Insight into infection level Want early detection and treatment of biofilm The implants needs to be able to function properly The product does not hinder his work or personal life The product has the lowest price or is provided for free Personal data protection	Is the user of the product Product will be used 24/7 Can test the prototype Decides if he will use the product Most of the users will not have technical knowledge	Needed to test the prototype The product needs to be suited to him so that it does not hinder his work or personal life Preferably a non-invasive product The product will be worn 24/7 The product should respect his personal data Acceptance of the product is crucial for success of the product The product needs to give insight into whether there is an infection or not The product needs to reduce biofilm formation The product should have the lowest price possible or be provided for free The product should be well-evaluated so the patient sees the potential of the product
Hospital	Is not able to perfectly monitor the status of a possible infection Wants to give the best health care possible Needs money from the insurance company Might have too many patients for the available resources Reluctant to proceed with major surgery for diagnostic purposes Hesitant to use less invasive diagnostic techniques which are developed by researchers because they need further evaluation^[2] Patients with biofilms usually have a medical history of antibiotic failure and infections ^[2]	Wants to be able to monitor the status of a possible infection If the biofilm can be prevented from forming, this would be better for the patient than giving treatment of the bioflim	Gives care to the patient Has the resources to treat the patient	It would be best if the biofilm would not form instead of treating the biofilm or removing the implant If it is not possible to prevent biofilm formation, then an early detection of the biofilm is favourable. After this, the biofilm should be removed as fast as possible
Family and friends	Care about the patient’s health and wellbeing	Want the patient to be healthy and that his well-being is ensured	Not all of them have a technical background	Want the best possible solution for the patient
Engineer	Designs the product	A product that meets the MoSCoW criteria which is mentioned in the requirements section	Must take into account the stakeholders into the design process	Should use the MoSCoW criteria to design the best possible product
Insurance	Provides the best possible care at the lowest price Wants to make profit	The costs of the implant / treatment of the biofilm should be reduced	If the product has a high price, money from the insurance is needed The product needs to be cheaper than other products or treatments in the long term	If the product has a high price, money from the insurance is crucial for the acceptance of the product The product needs to save health care costs in the long term
Manufacturing Company	Wants to invest in innovative products with low development costs Manufactures the product	Wants to make profit	Can manufacture the product Knows manufacturing and market potential	Needed to manufacture the product Can be used to gain insight into manufacturing and market potential
Society	Interested in high-quality and cheap health care Wants the patient to be as healthy as possible Are affected by antibiotic-resistant bacteria ^[2]	Wants a high quality and cheap product	Decides on the public image of the product	Needs to receive clear information about the product

Table 1: Stakeholders of the project

Cause-effect order

Our "Bye-O-Film" software represents a comprehensive solution designed to address the challenge of detecting and treating biofilm infections on prosthetic joints. In this section, we will delve into the key architectural features of our software, explaining why these features are crucial in delivering an effective tool for both patients and medical professionals.

Figure 2: Diagram showing how the CUG-China 2022 team’s ci-di-GMPT-induced promoter works. Created with BioRender.com

Goals

For each problem in Figure 2, a goal can be defined. The goals are usually the opposite statement of the statements mentioned in the text boxes in the Cause-effect order diagram. For instance, the first cause (a not properly functioning body part) can be formulated as the goal (a properly functioning body part). Preferably, the most fundamental goal should be used for the design of a product. The most fundamental goals are the ones in the first step of the goals cause-effect order diagram in Figure 2. When the fundamental goal is fulfilled, the rest of the goals will be as well. When it is not possible to realize the most fundamental goal, another goal should be chosen that is almost as fundamental but is realizable.

The first fundamental goal is to have a functioning body part. The project would become too broad if we would develop a solution for all non-functioning body parts. Other fundamental goals would be to have no bacteria in the environment of the implant. However, it is very hard to fully prevent bacteria from getting in contact with the implant. Other goals would be to make the conditions for bacteria to settle on the implant less favorable. Or make the conditions for the biofilm to form less favorable. However, until this moment there are no solutions yet to fully prevent all bacteria from settling on the implant and forming a biofilm. Therefore, it is needed to work on the next fundamental goals as well, namely reducing biofilm formation and informing the patient and doctor about the biofilm. This way the other goals in the cause-effect scheme will also be realized.

Assignment

As discussed in the previous section, the most fundamental goals that are possible to achieve are reducing the biofilm formation on the implant and informing the patient and physician about the biofilm infection. The design assignment is as follows:

Design a product for patients of 18 years and older with an orthopedic implant who are at high risk of infections that measures clinically relevant physiological changes that are a promising indicator for biofilm formation, inform the patient and doctor and which reduces the biofilm formed on the implant.

The following steps can be performed to fulfill the design assignment:

Find promising indicators for biofilm formation through literature research
- choose the best one for this project
Find promising methods to reduce biofilm formation
- choose the best one for this project
Find promising methods to inform the patient and doctor about biofilm formation
- choose the best one for this project
Combine the three previously listed components into one product
Test the previous components of the product
Discuss the results of the tests and provide feedback about the product to make it fulfil the most requirements.

The best solution will be the one that fulfils the requirements listed in the next section the most.

List of requirements

The MoSCoW criteria for the product are listed below. The M stands for must-have, the S for should-have, the C for could-have and the W for will not-have. The must-haves are mandatory for the product. The should-haves are important but not vital for the product. The could-haves would be good to have in the product but are less important than the must-haves or should-haves. The will not-haves are not a priority for the product in this project but they could be in another project. The stakeholder analysis (Table 1) was used to make the criteria. Some of the MoSCoW criteria are an estimate and need more research to confirm the exact requirement. However, it can already give a direction for product development and can always be adjusted if really needed. It is important for product development to start thinking about the requirements of your product while designing the product.

Must-have

Performance

The product can derive clinically relevant parameters that are an indicator for biofilm formation from the raw data of the sensor
The product can give an overview of the likelihood of biofilm formation in the patient for 12 hours a day
The usage of the device should not increase biofilm formation meaning that the average biofilm formation of 90 out of 100 persons that use the product over one week should be similar to the average biofilm formation over one week when they are not using the product.
The battery of the product lasts at least 24 hours or the battery of the product can be easily replaced without causing problems for the other must-haves and should-haves.
If the product has a battery, it should be possible to recharge it within 6 hours
The product should give a signal when it is not able to perform its function correctly

Safety

The product can withstand pH ranges between 4.0 and 7.0 if the product is attached to the skin ^[4]. If it is attached it is in contact with other parts of the body, the corresponding pH ranges should be looked up.
The product can withstand indirect sunlight for 16 hours a day for five months.
The product can withstand indoor light for 16 hours a day for five months.
The product can be used in indoor spaces where the temperature is between 10 and 30 degrees Celsius
The part of the product that is on the outside of the body has an IP69 rating (rating for water and dust) ^[5]
The product does not harm the body
1. The outside of the product is made of material that is biocompatible with the skin of the user and the other parts of the body the product is in contact with
2. The product does not have sharp pieces on the outside
3. The product does not emit dangerous levels of radiation
The product complies with relevant data protection legislation like the General Data Protection Regulation.

Safety

The product fits the body of adults with a BMI under 30.

Should-have

Performance

The product has a 95 percent selectivity (the ability to respond only to the measurand of interest)
The product gives feedback about the biofilm formation to the patient and doctor
The product gives suggestions for further steps to the patient when there is biofilm formation

Use

It should not take more than 180 minutes for 90 out of 100 users who finished secondary education to understand how to use the product properly.
The product does not irritate the skin of the user
The weight of the product fulfills the following requirement
According to ^[6], if the product is attached to the following body part the weight is not more than
1. 194,4 g for the collar area
2. 170,0 g for the shirt pocket
3. 113,8 g for the forearm
4. 186,4 g for the upper arm
5. 313,1 g for the pant pocket-front
6. 339,3 g for the pant pocket-back
7. 503,0 g for the waist-front (one side)
8. 853,0 g for the waist-front (both sides)
9. 513,2 g for the waist-back (one side)
10. 828,1 g for the waist-back (both sides)
11. if the product is not attached to the body of the user the weight is not more than
  1. 5000 g
The volume of the product fulfills the following requirement
1. According to^[6] , if the product is attached to the following body part of the user the volume is not larger than
  1. 49,3 cm3 for the collar area
  2. 92,0 cm3 for the shirt pocket
  3. 51,1 cm3 for the forearm
  4. 88,1 cm3 for the upper arm
  5. 62,7 cm3 for the pant pocket-front
  6. 59,2 cm3 for the pant pocket-back
  7. 92,8 cm3 for the waist-front (one side)
  8. 94,2 cm3 for the waist-back (one side)
If the product is not attached to the body of the user the volume is not larger than
1. 40000 cm3
The surface area of the product fulfills the following requirement
1. According to ^[6], the surface area of the product if it is attached to the body of the user should not be more than
  1. 31,3 cm2 for the collar area
  2. 44,1 cm2 for the shirt pocket
  3. 32,8 cm2 for the forearm
  4. 42,3 cm2 for the upper arm
  5. 39,9 cm2 for the pant pocket-front
  6. 45,3 cm2 for the pant pocket-back
  7. 43,4 cm2 for the waist-front (one side)
  8. 43,5 cm2 for the waist-back (one side)

Costs

The product costs less than the medical costs for an implant replacement plus infection treatment

Could-have

Performance

The product has a 95% reproducibility (the ability to produce a similar signature when the sensor is repeatedly exposed to a specific measurand)
The product has a 95% specificity (the ability to classify that the user does not have a biofilm on their implant when the user does not have a biofilm on their implant)
The product has a 95% sensitivity (the ability to classify that the user does have a biofilm on their implant when the user has a biofilm on their implant)
The resolution (the accuracy of the measurement of the measurand concentration) of the product is 95%)
The product gives an indication of the probable location of the biofilm infection
The product gives background information to the user about the biofilms in general
The product has a contact option to talk to the doctor for questions

Use

The product is non-invasive
1. No cuts in the skin of the user have to be made
2. As little as possible of the product is inside the body of the user
The product fits the body of adults with a BMI over 30

Will not-have

Use

The product can be used in other contexts than users with the risk of biofilm formation on their implants

Function analysis

The functions of the product are described in Figure 3. They are described as abstract as possible to make it easier to produce many concepts during the design phase of the product.

The function analysis is focused on the electrical sensor. The other part of the product is reducing the biofilm formation and biologically sensing whether there is biofilm formation. This will be done by using synthetic biology.

The function analysis for the electrical sensor is as follows: The first function is to connect material. Then some kind of energy needs to be transformed into another kind of energy (e.g. electrical energy) by a sensor. The energy needs to be transported to for instance an Arduino microcontroller. For this step, energy needs to be converted. The input energy needs to be transformed into different output energy. The output energy needs to be transported to a computer. For this step, energy needs to be converted. The energy needs to be transformed into information and after that, it needs to be stored. The last step is to disconnect the material.

Figure 3: Function analysis of the product

References

[1] M. Boon. (2021) “Analysis of a physiological sensor for stress measurement in office workers,” Groningen.

[2] Ronin, D., Boyer, J., Alban, N., Natoli, R. M., Johnson, A., & Kjellerup, B. V. (2022). Current and novel diagnostics for orthopedic implant biofilm infections: a review. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 130(2), 59–81.

[3] McConoughey, S. J., Howlin, R., Granger, J. F., Manring, M. M., Calhoun, J. H., Shirtliff, M., Kathju, S., & Stoodley, P. (2014). Biofilms in periprosthetic orthopedic infections. Future microbiology, 9(8), 987–1007.

[4] Lambers, H., Piessens, S., Bloem, A., Pronk, H., & Finkel, P. (2006). Natural skin surface pH is on average below 5, which is beneficial for its resident flora. International journal of cosmetic science, 28(5), 359–370.

[5] IP ratings | IEC. (n.d.). Www.iec.ch.

[6] Park, H., Pei, J., Shi, M., Xu, Q., & Fan, J. (2019). Designing wearable computing devices for improved comfort and user acceptance. Ergonomics, 62(11), 1474–1484.

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