Telemedicine Applications of Strip

One of the things that we liked about the strip we created is its application for telemedicine. Although it was very valuable for us to create a reader for our strips, initially we were thinking of going along the lines of having a cell phone take a picture of our strips in order to read them. Once the patient, or nurse, takes an image of our strip using a cell phone, they can send it to an off-site computer, which would analyze it for average color intensity, and send back a resulting glucose level- this would be based on experiments done previously. This process is illustrated below.


Some of the benefits of this process are:
1. The ability for a health care provider to go to poorer, and more remote areas, and use a cell phone to take images of diagnostic tests and send them back to a central facility expands the number of patients that can be reached.
2. The results for the glucose concentrations are stored in a database, and can be accessed by doctors as necesary.

We thought of some of the problems that may arise and posible solutions for them:
1. Changing ambient light- This could be solved by having a color gradient on the strip itselt, which would allow the color that eventually shows up to be matched to a color on the gradient by the computer, and so be calibrated.
2. Changing camera position- This could be solved by having a barcode on the strips that would allow the orientation of the image to be recognized by the computer- this technology does exist.

In the end, we like that our test strips will eventually be able to be used in a variety of situations, whether with the reader that we are developing, or with a cell phone, and computer application. The reader is a good solution for us to pursue first because it is cheap (camera cell phones are not so cheap), portable, easy to use, and can be used in areas with no cell phone reception (this actualy was one of the problems we learnt about in Nicaragua). There is a greater possibility of all patients having a glucose reader, but not of everyone having a camera phone. The reader was also designed with local production in mind, and that is another benefit for the local people.

Further Testing of Strips

After we had concluded that we could indeed achieve a color change by adding a concentrated glucose solution, with the concentrations of reagents that we had chosen, and by applying them in layers onto filter paper, we did some tests to learn more about the sensitivity and limitations of this method. 

Firstly, we created glucose solutions of 100 mg/dL and 150 mg/dL, and this was in order to test actual blood glucose levels on our strip. 100 mg/dL and 150 mg/dL are the concentrations glucose should lie between if the test was done at a random time interval (i.e., not after fasting for 8 hours, like some blood tests are done). When we applied these glucose concentrations to our strips, we saw a color change for the 150mg/dL, but a significant lack of change for the 100mg/dL solution. This was interesting, because it meant that our reagent concentration choices were quite good, and our strip was sensitive to tell the different atleast between the limits of real blood glucose levels. 

Secondly, we tested the order in which reagents should be applied to the filter paper. We had three reagents to apply, the dye (D0), Horseradish Peroxidase (P0) and Glucose Oxidase (G0), and we alternated the order of each. From the image, you can see that we found that the best order was the one listed above, and the one that we had initially used for our tests, dye followed by the peroxidase followed by the glucose oxidase. 

Medical Device Compass Chart

Colorimetric test strips were used for measuring glucose levels about 20 or 30 years ago, but then the technology was phased out in favor of the current glucometers, that use electrochemical reactions to measure glucose levels. The main problem with colorimetric strips was that there was no accurate way to read them and translate the color to a specific glucose level. The electrochemical reactions were able to be measured more accurately. It was because of this that the development of technology for measuring glucose concentration in the developed world was diagonal as shown on the chart.

What our goal was to create a way to read colorimetric strips accurately, so that we could develop a better way to measure blood glucose that was as effective as the current glucometers, but was a lot cheaper i.e., develop upwards on the compass instead of diagonally.

At the moment we are about halfway to our eventual goal, since our device is cheap, but needs to be more accurate before it can measure blood glucose to a similiar degree of accuracy and effectiveness as current glucometers.

Elevator pitch at the MIT Museum

So all of the D-lab teams presented a one-minute pitch about their project at the MIT Museum last Saturday. This is what I said about Glucotank:

“Diabetes is a disease in which the body cannot effectively regulate blood glucose levels. Thus, patients with diabetes have glucose levels which can fluctuate dramatically in a few hours. These patients could fall into low blood glucose levels, which can cause a coma, or high blood glucose levels, which can cause long term complications like kidney or even heart failure. Patients in developed countries typically measure their glucose levels four to five times a day which a glucose machine, also known as a glucometer. They drop a finger prick of blood onto a test strip, which the glucometer then reads to measure glucose levels. By measuring their own blood glucose levels, these patients can act quickly and correct for swings in their glucose concentrations – such as by eating sugary foods or taking an insulin pill. However, current glucometers are not appropriate for patients in developing countries. Test strips are expensive and proprietary, and poor supply distribution in developing countries prevents patients from easily getting compatible test strips and glucometers. This is a problem, because each year 6 million people develop diabetes, and 80% of these new cases of diabetes will appear in developing countries several years from now. We have developed an open-source platform for reading blood glucose levels, which can be locally manufactured and sold at a significantly lower cost than existing glucometers. Our test strips change in color intensity depending on the concentration of glucose, and our reader measures the color intensity to determine the approximate glucose concentration range. Thank you and be sure to check out our poster to learn more!”

Initial Prototype Video Comments (Part 2 of 2)

Three more comments about the initial prototype videos were made. I’ll summarize them below.

The third reviewer mentioned the possibility of using urine strips. The problem (I believe) with this approach is that glucose is normally not found in urine. Glucose transporters in the kidneys reabsorb almost all of the glucose filtered, so unless there is a lot of glucose in the filtrate such that not all of it can be reabsorbed, glucose will not appear in urine tests. Diabetics who have high blood glucose levels will have kidneys that excrete excess glucose, which can then be detected in urine. However, we want to be able to measure glucose concentrations at all levels. Also, I’m not sure how representative glucose concentration in urine is of glucose concentration in the blood.

The reviewer also challenged the idea of using a cell phone, making the point that not everyone has a cell phone. A question that I have in response is whether it would be simpler to provide a cell phone to the user, given that they are rather cheap, and also the point that the patient could benefit from a having a cell phone.

The reviewer also questioned the need for having software to read the results, or to send the measurement off to a doctor. I would respond that the software will be able to more accurately compare the reading to the standardized gradient, and that if the glucose concentration appears to be out of normal, the doctor can be notified (and the doctor can then read the data accumulated over time).

Lastly, this reviewer questioned the use of cell phones as a diagnostic tool. The reviewer proposed having a health worker come to the patient instead and read his/her glucose level. The health worker would then use the cell phone to transmit data. I would respond that the power of this technology comes from using what patients may already have (cell phone) and combining it with a need (reading blood glucose levels). Ideally, patients would want to read their glucose levels multiple times a day, so having a health worker visit them routinely might not be possible. Also, it might not be a bad idea to let the data collection and storage happen instantaneously after the measurements are made (so that the information does not become lost on random paper sheets). Of course, we could be wrong about our assumption that cell phones are widely available/accessible.

The fourth reviewer liked that fact that we had a multi-layered solution, which gives us flexibility in implementing this project is such a short time. The reviewer also liked the fact that we were creating a new platform for reading colorimetric assays that would eventually be open source.
The reviewer makes the neat point that we took an old technology and combined it with newer technology to create a product that can solve current problems. The reviewer also agreed with the idea of having a controlled light system and the CCD camera (since the test strip would be placed against the glass plate, and thus no outside light would reach the interior of the box). The reviewer suggested that we could build this with a cell phone light for the time being.

In addition, the reviewer suggests that we should better work out the details of the reader, and reduce the number of steps to use the reader down to 2 or 3. The reviewer also asks that we make a budget to make sure that the device will remain affordable. Surprising, this reviewer sounds a lot like our course instructor (=P).

The fifth (and last) reviewer made the great suggestion of collecting more information: How much do we currently know about the needs of diabetic patients? What challenges do they currently face? How are they meeting those challenges? We know that diabetics in developing countries certainly are not getting their blood glucose levels checked several times a day, if at all. What risks does this pose for the patient?

We should investigate the living conditions of diabetics, what access to medical care they have, what are conventional diabetes management procedures in the region.

Commenting on our video, the reviewer said that we could have used the doctor-patient scenario in the video to better explain diabetes, since the audience might not know about the basics of diabetes and why testing is important. This is a great idea. The reviewer also suggested that we make an elevator pitch (which will come shortly!)

Thanks to all of the reviewers! We certainly got some good ideas on directions that we should pursue.

Initial Prototype Video Comments (Part 1 of 2)

We’re starting to receive comments about the about the initial prototype videos we made. I’ll summarize the comments we currently have.

The first reviewer did not understand why there was a separate cell phone application and a self-contained diagnostic machine. The reviewer liked the idea of test strips, but did not see the need for the gradient, saying that the strips did not need to be most accurate.

My response: We did not make it clear that the colorimetric assay could not be precisely read by the naked eye. Having a machine to read it (by converting it into grayscale and then comparing it against a standardized gradient) is more accurate. But then, one could argue that our test strips do not need to be that accurate – having 6 boxes is enough. I would say, though, that we should not limit our initial conceptual designs to be “just approximate enough” when we know how to make it better – if we are successful, we might even be able to market our product in developed countries. So perhaps we should make different technologically advanced levels of our product for different types of consumers.

The second reviewer liked the idea of having different levels of reading, which allows for redundancy – the lowest is reading the strips with the naked eye, the middle is using the cell phone, the highest level is using the CCD camera. The reviewer also liked the idea that one could save data on cell phone or send it to a central database (for the doctor to monitor the patient’s health).

The reviewer misunderstood how we plan to calibrate the strips. We are not using the white background to calibrate the strips - instead, we are using the gradient that appears next to the test strip for calibration. The reviewer makes a good point about the fact that shadows could significantly distort the reading – perhaps we could place two standardized calibration gradients on the strip – one on either edge (left and right).

The reviewer also makes the great point that we should have some detection method that asks the user to retake the photo if some condition fails (the background is not uniform because of a shadow). Indeed, having “sanity checks” increases the reliability of our program – it ensures that the reading falls into a certain range. Perhaps our program can even return a confidence estimate. Another simple check would be to display the result to the user and wait for a confirmation response.

The reviewer questioned how we were going to exactly develop the box – the reviewer pointed to the fact that it could potentially be cheaper (in addition to being more accurate), but it might be too complex, given the limited time that we have.

Glucophone

One of our ideas is to create a glucophone – the glucometer would be attached to the cell phone. An increasing number of people in developing countries have cell phones, so we thought that it would be a neat idea to combine glucose measurement and data collection with cell phones.

The pros of such an approach are that the cell phone can be used to display, power, and store data. The data can also be sent to a central database for remote patient monitoring. The doctor could have access to this data, and thus look at long terms trends in the patient’s blood glucose concentration should problems arise.

The cons of such an approach are that such a technology is expensive to develop and is technologically challenging to build(given the few weeks we have remaining in D-Lab Health). It would also be difficult to design a component attachable to all cell phones. There is also a company already doing this: http://glucophone.net/ However, it is not clear if this company still exists. Their copyright label at the bottom of the webpage goes to 2007 only…

Why bother measuring blood glucose concentrations?

Someone we talked to today asked a good question. How does knowing one’s blood glucose concentration help a diabetic patient? The goal of diabetes management is to keep a diabetic’s blood glucose concentration with the normal values of 70-130 mg/dl – this is called glycemic control. If the patient manages to keep their glucose concentration in this range, then the patient can protect him or herself from the negative consequences of diabetes. Poor glycemic control means that the patient allows his or her glucose concentration to stay in the range of 200 to 500 mg/dl over several months. This can have severe health consequences.

Diabetics typically measure their blood glucose levels 4 to 5 times a day. This allows patients to act quickly to correct for swings in their glucose concentrations – for instance, if they find that their glucose concentration is too low, they can eat something sugary to prevent fainting, and if they find that their glucose concentration is too high, they can take an insulin pill. Thus, by knowing their own blood glucose levels on an almost hourly basis, diabetes can work to keep their own blood glucose levels within the healthy, normal range.

Diabetes in developing countries

Developing countries are increasingly baring the burden of diabetes. Rapid cultural changes, increasing urbanization, dietary changes have lead to an increase of diabetes in the developing world. Less than half the people with diabetes in developing countries are diagnosed, and two-thirds of deaths caused by diabetes occur in developing countries. It is predicted that 80% of all new cases of diabetes will appear in such countries by 2025.

Below are prevalence estimates of diabetes in 2007:



And in 2025:



Notice the prevalence of diabetes in Central America (in particular, Nicaragua, where D-Lab Health visited this past IAP)

Our product has the potential to serve people in developing countries who cannot access currently available but expensive glucometers.

What is diabetes?

Diabetes is a disease in which the body cannot effectively regulate blood glucose levels. The patient’s glucose levels can fluctuate dramatically within a few hours. The patient faces health risks if their glucose concentration falls outside the normal range of 70 to 130 mg/dl. If the patient has low blood glucose, the patient might develop short term complications, such as a coma. If the patient has high blood glucose, the patient might develop long term complications, such as kidney or heart failure.

Diabetes has reached epidemic levels around the world. The disease currently affects about 246 million people, which is 6% of the world’s adult population. Each year, 6 million people develop cases of diabetes. Diabetes also causes 3.5 million deaths each year. Diabetes is the largest cause of kidney failure, and it increases the risk of heart disease and stroke.

More statistics about diabetes can be found here: http://www.worlddiabetesfoundation.org/composite-35.htm

How cheap will this actually be...?

We keep talking about how important it is for our reader and strips to be cheap so I guess we should go into the cost breakdown of these components a bit more. I'm just going to talk about the reader in this post. The cost of building our prototype reader is about $10-15 depending on where you get parts from, but we estimate that the actual device could be produced for under $10. It should be cheaper because a final design will need less of our currently expensive parts because the circuit itself can be redesigned that way and because some parts that are currently useful for testing the device will no longer be necessary. Buying parts in bulk also should reduce costs somewhat. The housing is currently cardboard and eventually would probably be plastic, which is generally pretty cheap.


Another cool thing about the device is that it has the potential to be locally manufactured (easier with a basic analog reader like this than with a more complex normal glucometer). It also could be much easier to repair.

Future directions for reader

Team Glucotank wants to continue working on this project so I'm going to talk about some of our ideas. Now that we have a working prototype, we're looking at the ways in which we could improve or extend it. We would really like to eventually have a device that lights up a panel of 10-15 LEDs, meaning that the ranges of glucose concentration indicated will be smaller. Right now we can basically only give a high/medium/low reading. This is useful for screening or very basic monitoring. This is important given that there is very little monitoring at all right now but still not the level of accuracy we want to achieve. Even though a panel of LEDs would still only give ranges of glucose concentration, this is really all that is needed for patients. We realized this when talking to someone looking at our display at the museum. Since recommended insulin dosages are based off of ranges of glucose concentration, patients can just be told how much insulin to take based on whichever range our device indicates. In this way, our device can be simpler but still as accurate from a practical standpoint as a typical glucometer that gives an actual numerical reading for glucose concentration.

We are also playing around with different ideas about how we could take our design and make it something that applies to different types of colorimetric diagnostic strips. Rather than having a circuit that works only with our set glucose concentration ranges, it would be more versatile. We want to look into using a simple processor to compare light intensity from a sample to light intensity from a gradient scale on the strip (similar to our first design). With something like this, different types of strips would all have their own control gradient scale and could be read by the same device. Programming something to perform these more complicated operations could definitely be tricky though.

At the museum we spoke with one of the Dlab ICT instructors about collaborating with students from his class on this project. He's very interested in sitting down and learning more about the details and capabilities of the chemistry involved with our glucose strips. We're thinking of combining our understanding of the biochemistry/health/community aspects of this project and his students' knowledge of how to actually build these more complex circuits and write more complicated programs (for this reader deivce and perhaps for cellphones eventually). At this point we have definitely learned that a big part of getting this type of project to succeed is knowing how to ask the right questions from the right people...so this seems like a great potential partnership! Also, some of the people who helped us out with these initial designs are very interested in continuing to help us out, so things are looking pretty good!

Pugh Chart

Here's our pugh chart - it shows the different options we weighed when deciding how to approach our problem. It's gone through several different versions so far, this is the latest one (it was updated by Yi and Mike). We weighted the different design parameters differently to indicate the importance we think they have to our device design.

The design parameters that we gave the most weight were long-term effectiveness, reliability, accuracy, economy, maintainability, and of course, safety. Long-term effectiveness includes the device's ability to address immediate and long-term needs and its ability to do so in a efficient manner, both of which we consider crucial. Reliability, accuracy, and safety are all important in ensuring that our device will actually help our patients monitor their blood glucose levels in a way that is useful to them and that the device itself cannot cause them any further harm. Economy and maintainability are important because if these aspects are lacking, then even a "perfect" device will never make a difference to patients in this developing setting because it will remain inaccessible or unuseable to them.

Homeless Diabetes Patient

Notes from talking to a homeless diabetes patient:
-Strips are the most expensive part; Medicare pays for strips
-Tests twice a day, at least once a day. Because he has Diabetes I, he can't use pills and can only use injections of insulin.
-Background: He used to be a drug addict, now he's off. First in his family to get diabetes I. Has hypertension. Used to work at Shaws. Wants to get out of the homeless shelter, but not sure if he can because of medical issues.
-Has had diabetes for 18 years. Now familiar with the numbers (highs and lows). Knows what can eat, what food causes fluctuations. If number goes over 300 (did not know it was mg/dl), he will have to go to the hospital. He may have to stay in a hospital for 4 or 5 hours - sometimes even 4 to 5 days. Records glucose measurements for nurses to check. When levels are low, nurses personally make sure he uses the glucometer and monitor levels properly.
-He has to worry about glucose levels getting too low as well. He can recognize symptoms of it being too low. He may have trouble walking or operating. But sometimes the complications occur too fast for him to do anything about it. He may pass out or get seizures - doesn't know if it is due to glucose level being too high or too low. He said he'd be lucky it he only had seizures once in four or five months. One time he was in the bathroom when he had a seizure, fell on a urinal, and broke half his face. He was unconscious for 6 days.
-Regarding lancet: not painful, used to it. Just need 1 drop of blood. Finger seemed to heal very well, not need bandaid- just put on some alcohol. The strip never touches the meter so the meter doesn't need to be cleaned.
-When asked if he would test more if the strips were cheaper, he said maybe and maybe not because sometimes he doesn't want to know, fear that it might be high.
-Teared up with appreciation for the nurses at the shelter - saving his life, regarding seizures and being unconscious.

Old style colorimetric glucometer

"An older style portable blood glucose meter. A blood sample is applied to an inserted strip (see image above) and color changes caused by reaction with blood glucose are measured by the meter." Wikipedia

Poster problem/background/specs

Problem
At the Regional Hospital in Esteli, Nicaragua, they only had one glucometer shared among 15 clinics. As a result, diabetes patients were not able to monitor their blood glucose levels on a regular basis, a crucial part of controlling their disease. The key expense of glucometers is the test strip, which is proprietary. Our design challenge is to design a fast, cheap, safe and reliable way of measuring glucose levels that can be used widely by diabetes patients, even in poor resource settings.

Background
Glucometers are essential for monitoring glucose levels in diabetes patients. Diabetes patients lose the ability to either produce or respond to insulin, a key protein that signals cells to take in glucose. A typical diabetes patient has fasting plasma glucose level at or above 126 mg/dL. Depending on patients’ medication dosage, level of exercise, and food intake, their glucose levels can fluctuate dramatically. Persistent hyperglycemia can lead to long term complications like heart failure, while hypoglycemia may cause short-term complications like comas.

Design Specifications:
• Sample Volume: 0.3ul to 10ul
• Accuracy: +/- 10-15%.
• Testing sites: Mostly fingertips
• Processing time: 3 to 60 seconds.
• Frequency: Type 1 diabetics may test up to 10 to 12 times a day.
• Whole blood glucose vs. plasma glucose: plasma glucose 10-15% higher

Testing the effectivenes of the Colorimetric Assay

Before we could focus on making our test strips, we wanted to test and see if we could even see any color change with the reagants that we ordered. The reaction was supposed to work as discussed in one of the previous posts by YW.

Method:

1. Pipette the dye onto filter paper, let it dry

2. Pipette horseradish peroxidase onto the same spot, let it dry

3. Pipette glucose oxidase onto the same spot again and let it dry

4. Pipette glucose solution onto the spot containing the reagants, and hope for a color change.

Results:

We did see a color change!

After getting this intial results, we did several other experiments to test the robustness of this colorimetric assay, which will be discussed in later posts.

Picture

1) Finished product
2) Glucotank uncovered/in the process of making it.

Picture

Design Considerations

For our design considerations, we creative a list of the different considerations we should look at and weighted by their applicability to our situation. Here they are with the weights (3 - highest, 1 - lowest):

Long-term Effectiveness 3
Speed of Use 2
Reliability 3
Accuracy 3
Economy 3
Accessibility 2
Usability 2
Simplicity 2
Practicality 2
Maintainability 3
Aesthetic Appeal 1
Environmental Friendliness 1
Safety 3
Versatility 2
Efficiency 2
Marketability 2
Ease of Integration 1

What's available now...

So next we took a look at some of the existing technologies for glucometers and other methods for measuring blood glucose levels. We found that the predominant technologies on the market today are glucometers that directly measured blood glucose levels from a blood sample taken from the user. This was preferred because the technology has been around for quite a while. There is a newer technology that measured glycosylated hemoglobin (hba1c) levels in blood, which seems to be a better and more consistent indicator that just measuring highly-variable blood glucose levels. However, this technology is still in it's infancy stages in terms of development, and available readers are too expensive for our purposes.

Some cooler technologies that exist are devices that utilize telemedicine principles, such as the Glucophone, a glucometer attachment to a standard Samsung phone that will not only read the blood glucose level but will also send the data to a central database for data-tracking and trend analysis.

Our Design Challenge

Before we each jump in to blog about our project, we thought it would help to have a description of the problem that we are trying to solve, and a short statement of our design challenge. 

As part of Dlab Health, we went on an information collection trip to Nicaragua. In one of the poorer regions, Esteli, we visited the Regional Hospital and discovered that they only had one glucometer that was being shared between 15 clinics! As a result, diabetes patients were not able to monitor their blood glucose levels on a regular basis, and so were not able to control their disease. Not keeping glucose concentrations within safe margins increases the risk of diabetes related serious conditions. 

The reason that all the polyclinics and the regional hospital in Esteli were sharing a single glucometer was because of the expensive test strips. Though glucometers are commonly donated, boxes of test strips are not, and since these test strips are proprietary they could not afford to keep buying them. For example, we found a glucometer online for $40, however the test strips that had to be used with it cost $40 for a pack of 25. Thats over a $1 per strip! 

Therefore, our design challenge is to design a fast, cheap, safe and reliable way of measuring glucose levels that can be used widely by diabetes patients even in poor resource settings. 

- Allen, Mike, Deepali, Yi and Priyanka