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Revision as of 18:42, 20 October 2019

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Introduction

Through different influenza screening method, we can collect the testing data to the Cloud database of influenza.
Therefore, we can predict where the epidemic influenza will break out, give standard precaution, and administer the medication to patients to prevent the spread of influenza.

screening High false negativity
High price
High time cost
Not enough added value
Prediction Insufficient spatial resolution
Insufficient time resolution
Diversity
Prevention Unwanted price
Lack of people’ compliance
Treatment Side effect

If this formula of public health can be utilized to combine the upstream and downstream tightly, it can give the disease a heavy strike and suppress the expansion.
However, the four key factors, screening, prediction, prevention, and treatment, have problems below that lead to the vulnerability of disease control.


Let’s see how our design reconnect these parts!

Rapid diagnostic strip

Strip design

In the reagent, there are aptamers that can bind with influenza virus.
One end of the aptamer is bond with dye, and the dye is connected with biotin.
On the strip, there is a DNA strand which complements to the aptamer at the check point as test group, and another check point is avidin which is referred to as control group.

The relation of biotin and avidin: Binding with high specificity and high affinity.

The principle of results:
Negative:
The aptamers in the solution will bind with the complementary DNA at the check point of test group, and the biotin which labeling aptamer will bind with the avidin at the control group.
The result of negative displays two lines because the aptamer is carried with nanogold.


Positive:
In the existence of influenza virus, the aptamers are bond with the virus.
This situation leads to the configuration change of aptamers and the unbinding of complementary DNA at the check point of test group.
However, the biotin will still bind with the avidin at the check point of control group.
Thus, the result of positive displays only one line.



casing design

There are two versions of influsensor: Easy-to-use version and Professional version

Easy-to-use version of influsensor Professional version of influsensor
User Doctors in countryside or developing country Clinics and hospitals
Function Rapid screening Data uploading and precise surveillance

Easy-to-use version of influsensor

There are two components on the rapid diagnosis strip:

  1. The area for placing sample
  2. the window for observing the result.

There are three check points on the strip:

  1. The aptamer for detecting influenza A as test group
  2. The aptamer for detecting influenza B as test group
  3. The avidin for binding with biotin as control group. Because of the design of control group, we can assure that the reagent flow through the whole strip.

The outer casing of the rapid diagnostic strip is 3D printed with green material for the protection of the Earth.

Professional version

Utilize machine to read the testing data to acquire the precise information and upload the data to the Cloud database in time.
The professional version can achieve the greatest use of the predicting system.
Also, the data can be submitted through the internet and process subsequently.


User guide:
The throat swab is specially designed to have the reagent inside the swab tube.
After taking the sample from tonsil with the designed throat swab, doctors will
1.Squeeze the back end of the swab for letting the reagent flow to the fore end to meet the sample on the cotton.
2.Pipet the reagent with sample.
3.Put the swab to the placing sample area on strip directly.

The reagent will diffuse the reagent mixed the sample, and get the result afterwards.
The whole process can be completed with only five minutes and the manipulation is simple.
Later, upload the inspection data to the Cloud through the Internet and the authority concerned will assist the subsequent processing.

Characteristic
Low Cost, Fast Production and Development, High Stability, Low False-negative Rate, and Animal Free.

Low Cost
Description:
The aptamer is made of nucleic acid so that we can synthesize the sequence directly.
However, antibodies are proteins that need cells to mediate its production. That is the reason why the cost of antibody is expensive.
The advantage for the public health:
With the advantage of low cost, it means we can use the aptamer rapid diagnostic kit as a routine examination.
When we doubt that a patient is infected by influenza, the kit can be used as a primary diagnostic test to increase the spatial and time resolution of the data and prevent the spread of the virus under unclear clinical symptoms which are because of the differences of Individual physique.
The huge data which include the position and time can be submitted to the database as the use of epidemic prevention.

Fast Production
Description:
The component of the aptamer is nucleic acid so that we can synthesize the aptamer through PCR.
However, antibodies are proteins that need the processes of cell culture, protein extraction, and protein purification.
That is the reason why the aptamers can be produced fast.
The advantage for the public health: For emerging infectious disease such as Ebola, the time cost of one month may pay the price of thousands of people’s lives.

Fast Development
Description:
Aptamers are selected by the method of SELEX, so we can find out the target nucleic acid with only two weeks.
However, if we want specific antibody, we need to inject the antigen to the mouse. After taking out the spleen, make the B cells and the tumor cells to fuse together, then we can finally start to produce the antibody. It takes about three months to get the target antibody.
That is the reason why one of the advantages of the aptamer is fast development.
The advantage for the public health: The advantage of fast development is the same as the fast production. For emerging infectious disease such as Ebola, the time cost of one month may pay the price of thousands of people’s lives.

High thermal stability
Description:
The aptamer is a short DNA fragment so that it can afford the denaturation pressure of high temperature and turn back to functional structure after the ambient pressure is removed.
However, the antibody cannot turn back to functional structures after denaturing because its structure is protein.
The advantage for the public health:
With high stability, the storage life of products can be extended and the amount of damage can be reduced. We can provide highly efficient medical care to the people lived in remote districts or under extraordinary circumstance.

Low False-negative Rate
Description:
The biggest problem of the antibody- type diagnostic is the high false-negative rate. The high affinity of the aptamer can effectively lower the possibility of false negatives.
The advantage for the public health:
We can reduce the potential infectious source to suppress the prevalence of the disease and acquire the accurate information for epidemic prevention.

Animal Free

Description From the paragraph of Fast Production and Development, we know that the production of antibodies is using the spleen of mouse as raw material, and it will consume a large amount of animal’s lives.
As a medical product of the new era, when we use animals as tools for production, we should adopt the idea of animal welfare theory.
We should use animals as experiment materials only under necessary circumstance and should ease their pain.
Our product indeed reduce the unnecessary sacrifice of animal’s lives.
We achieve the goal of living in harmony with the animals.

User’s manual

The Public:
Using rapid diagnostic strip as household appliance for prevention of influenza.
Uploading the inspection data to the Cloud.

Doctors:
Using rapid diagnostic strip for diagnosing and preventing influenza.
Uploading the inspection data to the Cloud.

Government:
Using rapid diagnostic strip, and ecological monitor of wetlands as long-term surveillance system.
Uploading the inspection data to the Cloud.

CSMU_Taiwan Influsystem

CSMU_Taiwan System

Screening

  1. Rapid screening
    1. Principle

      In the reagent, there are aptamers that can bind with influenza virus.
      One end of the aptamer is bond with dye, and the dye is connected with biotin.
      On the strip, there is a DNA strand which complements to the aptamer at the check point as test group, and another check point is avidin which is referred to as control group.

      The relation of biotin and avidin: Binding with high specificity and high affinity.

      1. Sample is pre-mixed with the reagent
      2. The principle of results:

        Negative:
        The aptamers in the reagent will bind with the complementary DNA at the check point of test group, and the biotin will bind with the avidin at the check point of control group.
        The result of negative displays two lines because the aptamer is carried with dye.

        Positive:
        In the existence of influenza virus, the aptamers are bond with the virus.
        This situation leads to the conformational change of aptamers and the unbinding of complementary DNA at the check point of test group.
        However, the biotin will still bind with the avidin at the check point of control group.
        Thus, the result of positive displays only one line.


    2. Design

      There are two versions of influsensor: Easy-to-use version and Professional version

      Easy-to-use version of influsensor Professional version of influsensor
      User Doctors in countryside or developing country Clinics and hospitals
      Function Rapid screening Data uploading and precise surveillance
      Easy-to-use version of influsensor

      1. There are two components on the rapid diagnostic strip:

        the area for placing sample and the window for observing the result.

      2. There are three check points on the strip:

        the aptamer for detecting influenza A as test group, the aptamer for detecting influenza B as test group, and the avidin for binding with biotin as control group.
        Because of the design of control group, we can assure that the reagent flow through the whole strip.

      3. The outer casing of the rapid diagnostic strip is 3D printed with green material for the protection of the Earth.

      Professional version

      Utilize machine to read the testing data to acquire the precise information and upload the data to the Cloud database in time.
      The professional version can achieve the greatest use of the predicting system.
      Also, the data can be submitted through the internet and process subsequently.


      User guide:
      The throat swab is specially designed to have the reagent inside the swab tube.
      After taking the sample from tonsil with the designed throat swab, doctors will

      1. Squeeze the back end of the swab for letting the reagent flow to the fore end to meet the sample on the
        cotton.
      2. Pipet the reagent with sample.
      3. Put the swab to the placing sample area on strip directly.

      The reagent will diffuse the reagent mixed the sample, and get the result afterwards.
      The whole process can be completed with only five minutes and the manipulation is simple.
      Later, upload the inspection data to the Cloud through the Internet and the authority concerned will assist the subsequent processing.

    3. Characteristic

      Low Cost, Fast Production and Development, High Stability, Low False-negative Rate, and Animal Free.

      1. Low Cost

        Description:
        The aptamer is made of nucleic acid so that we can synthesize the sequence directly.
        However, antibodies are proteins that need cells to mediate its production. That is the reason why the cost of antibody is expensive.

        The advantage for the public health:
        With the advantage of low cost, it means we can use the aptamer rapid diagnostic kit as a routine examination.
        When we doubt that a patient is infected by influenza, the kit can be used as a primary diagnostic test to increase the spatial and time resolution of the data and prevent the spread of the virus under unclear clinical symptoms which are because of the differences of Individual physique.
        The huge data which include the position and time can be submitted to the database as the use of epidemic prevention.

      2. Fast Production and Development
        Description:
        The component of the aptamer is nucleic acid so that we can synthesize the aptamer through PCR.
        However, antibodies are proteins that need the processes of cell culture, protein extraction, and protein purification.
        That is the reason why the aptamers can be produced fast.

        Aptamers are selected by the method of SELEX, so we can find out the target nucleic acid with only two weeks.
        However, if we want specific antibody, we need to inject the antigen to the mouse. After taking out the spleen, make the B cells and the tumor cells to fuse together, then we can finally start to produce the antibody. It takes about three months to get the target antibody.
        That is the reason why one of the advantages of the aptamer is fast development.

        The advantage for the public health:
        For emerging infectious disease such as Ebola, the time cost of one month may pay the price of thousands of people’s lives.

      3. High Stability

        Description:
        The aptamer is a short DNA fragment so that it can afford the denaturation pressure of high temperature and turn back to functional structure after the ambient pressure is removed.
        However, the antibody cannot turn back to functional structures after denaturing because its structure is protein.

        The advantage for the public health:
        With high stability, the storage life of products can be extended and the amount of damage can be reduced. We can provide highly efficient medical care to the people lived in remote districts or under extraordinary circumstance.

      4. Low False-negative Rate

        Description:
        The biggest problem of the antibody- type diagnostic is the high false-negative rate. The high affinity of the aptamer can effectively lower the possibility of false negatives.

        The advantage for the public health:
        We can reduce the potential infectious source to suppress the prevalence of the disease and acquire the accurate information for epidemic prevention.

      5. Animal Free

        From the paragraph of Fast Production and Development, we know that the production of antibodies is using the spleen of mouse as raw material, and it will consume a large amount of animal’s lives.
        As a medical product of the new era, when we use animals as tools for production, we should adopt the idea of animal welfare theory.
        We should use animals as experiment materials only under necessary circumstance and should ease their pain.
        Our product indeed reduce the unnecessary sacrifice of animal’s lives.
        We achieve the goal of living in harmony with the animals.

Prediction

User’s manual

Government:
Using AI to predict the subsequent flu trend of expandingby utilizing the Cloud database of influenza.


AI

  1. Background

    The region with traffic congestion can be the breeding sites of viruses. If we want to predict the outbreak of the disease, we need data with high resolution to reduce the amount of incorrect information.

  2. Efficacy

    By the location that virus rage through currently to judge which region the virus might emerge. For example, if we find the influenza virus emerging in certain area of a town, there is a chance that the disease breaks out in other towns or countries nearby. Thus, we can take preventive measures to prevent the outbreak.

  3. Design

    upper picture...lower picture..


    key concept...


    Final system...


  4. The advantage for the public health

    Intensive database...

Prevention

User’s manual

The Public:
Using air purifieras household appliance for prevention of influenza.

Doctors:
Using air purifierfor preventing influenza and administer the prophylactic drug.

  1. Air purifier
    1. Background

      The outbreak of flu usually starts from a group of people with weak immune system, such as the people at school, hospital, and nursing home. Besides, the latent period of virus is 2 days. The viruses was spread before the symptom appear, and the flu outbreaks. If we can find out the virus in the latent period, we can surely prevent the outbreak of a flu epidemic. That is why we design the air purifier which can detect the influenza virus promptly.

    2. Design

      Inside the air purifier, we can place the chip of aptamer that can sense the influenza virus. When the droplets with virus are in the air, the virus will connect the aptamer on the chip, and then the connection will change the electrical characteristics such as changing the resistance of the resistor. The air purifier will tell the users that there are viruses in the environment and take preventive measures against the virus.

    3. Advantage

      We can combine the data collected from the air purifier with the Cloud database. In contrast to the inspection data, the locale data include the data of the range of clinics. The data of fixed surveillance system (spot monitoring) can also be used for another aspect of analyzing. With these two kinds of data, we can give abundant information to the Cloud database for acquiring more precise prediction.

Treatment

User’s manual

Doctors:
Using Anti-HA drugto save the patient with lower cost.

Anti-HA drug

  1. Background

    If the influenza virus want to invade cells, they all need a common key to open the door of cells. The key is hemagglutinin (HA). Therefore, if we can block the hemagglutinin of the influenza virus, we can stop the invasion of virus and prevent the expansion of the disease.

  2. Design

    We use the method of SELEX (systematic evolution of ligands by exponential enrichment) to select out the aptamer for H1 and H3. The way that we test the efficacy is observing the level that the aptamer affect the TCID50 of the virus. The efficacy testing method is hemagglutination assay. Using different concentration of the aptamer to mix with quantified amount of the virus and observe the level of hemagglutination.

  3. Advantage

    Compared with the intracellular drugs, the anti-HA drug composed of aptamer act extracellularly so that we can reduce the side effects of biochemical metabolism that occur in most of the drugs. In addition, drugs are located in the body fluid, so we also take the allergy problem into consideration. It is the advantage of the aptamer! When it comes to general medicine and therapeutic antibody, they are all macromolecular complex compounds. By contrast, the molecular weight of the aptamer is small and DNA is a common substance in the body, so the antigenicity of the aptamer is low. Therefore, the possibility of having side effects is reduced significantly when compared with general medicine.

Development potential

other application of aptamer

Anti-virus spray

  1. Background

    The influenza virus is usually spread by the way of disease cluster in the enclosed places such as hospitals, schools, and offices. If we can stop the invasion of the virus, we can reduce the possibility of the outbreak. That is the reason we have the idea of anti-virus spray.

  2. Design

    Select out the aptamer for the hemagglutinin of influenza then add them into the water. We can sprinkle the droplets containing the aptamer by sprayers or air coolers. When the droplets meet the virus in the air, the aptamer can bind the hemagglutinin of influenza, which means we destroy the key for virus to invade and inactivate the virus, achieving the efficacy for preventing the disease.

  3. Advantage

    General disinfectants cannot be sprayed into the air for preventing. Take alcohol as example, the nature of flammability may cause dangers. Take liquid bleach as another example, the high toxicity will stimulate the respiratory tract. Yet, the aptamer we selected is just a fragment of DNA. The aptamer will affect the virus only and there is no harm for human beings.

  4. Obstacle

    When releasing the free DNA fragment, we cannot assure the influence of the enviornment. However, we consider the product promising as long as the safety problem can be solved.

Broad application of aptamer

Taking influenza as a start, we can construct a medical system based on aptamers. We can expand our system horizontally and vertically. In horizontal aspect, we can expand the system to different species. In vertical aspect, we can develop aptamer-based systems of various kinds of diseases. Highly efficient suppression of species originally should be the natural enemy of creatures, mostly various kinds of disease. Diseases even attack the conservative target of different kinds of species to solve the problem of the competition relationship between hosts and parasites. The Red Queen hypothesis says “Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”
That is the concept!


We take avian flu as example below.

  • Background

    We can classify the bird species into two group: wild fowl and poultry.

    Wild fowl:
    We can classify the wild fowl into the groups of migratory birds and resident birds.
    For migratory birds, they are the source of introducing new virus gene, causing other species of birds transforming the low pathogenic avian influenza strain into highly pathogenic avian influenza strain.
    For resident birds, they act as the bridge between the migratory birds and the poultry. They are also the source for viruses to recombine their genes.

    Poultry:
    We can classify the poultry into the groups of waterfowl and terrestrial bird.
    For waterfowl, they are hosts for storing the virus and usually appear asymptomatically. Therefore, it is difficult for veterinarians to find out, and the disease spreads silently. What is worse is that the breeding equipment of waterfowl are displayed openly, so that the waterfowl contacts the wild birds more frequently and increase the possibility of spreading the disease. Moreover, waterfowls are like a culture room of viruses because of the low surveillance ratio.
    For terrestrial bird, they are the primary victim that we care about. It always cause a large amount of deaths when breaking out the avian flu. Because of the enclosed environment for breeding the terrestrial bird such as chicken, they are not easy to be infected by the wild birds. The main route of infection is because of the individual causes, such as the cross contamination of feed carriers and transport vehicles. It is difficult to judge which one is the route of infection because the complicated interaction. Furthermore, the labor cost and time cost of screening are considerably high. It is hard to do the general survey, causing the leakage of epidemic prevention.

  • Screening

    Poultry:
    The government can regulate the host of hennery to set the air purifier on the fence. We can detect the droplets of the chicken and upload the inspection data to the Cloud database simultaneously. Not only we avoid the inconvenience of census and the asymptomatic infection spreading, but we acquire higher quality data for analyzing subsequently.

    Migratory bird :
    The aim to inspect the group of migratory bird is collecting the strains of the virus. Usually, only 2 to 3 percent of the stool samples collected in traditional way are positive. Applying the model of rapid screening can significantly lower the transportation cost, time cost, and the time pressure for the referral laboratory.

  • Prediction

    We can collect the data from henneries and construct a three-dimensional graphic with a number of cases and a timeline. Afterwards, we can get the characteristic through AI and predict every possible situation. In conclusion, when a hennery have cases of avian flu, we can know how many henneries are in the high risk to be infected. Cleaning, disinfecting, or taking the prevention measure below are the method we can use to minimize the loss of henneries.

  • Prevention

    Anti-virus spray: In the high risk period, we can spray the droplets containing selected aptamer into the air to stop the invasion of the avian influenza and reduce the use of antibiotic prophylaxis. As a result, we can prevent the generation of the antibiotic resistant bacteria and make chickens become healthier.

  • Treatment

    For the epidemic prevention in animals, treatment is not the main point because of the high cost.