CC BY
5DOI: 10.24412/cl-37100-2023-12-180-184
V. Petrov, Dr. Y. Berdichevsky Use of TRIZ tools in biomedical research
ABSTRACT
Goal. To show that TRIZ tools in existing or adapted form can be effectively used in biological and medical research.
Novelty. This topic is still insufficiently described and covered in the worldwide TRIZ community. In the past, the use of TRIZ in biology was mainly represented by the use of bionics, an approach proposed back in his time by G. Altshuller.
Method. We applied the tool comparison method, studied the patterns of development of biology and medicine with TRIZ tools and adapted some TRIZ tools for the needs of biomedical research.
Results. Methodological recommendations on the use of specific TRIZ tools as well as examples of their successful use are provided.
The article provides an analytical review of this topic, comparing the tools, methods, and patterns in the development of biology and medicine with TRIZ tools. Implementation of TRIZ tools for biomedical research. Examples of the use of various TRIZ tools in biomedical research are provided, including examples from the personal experience of the authors.
Keywords: TRIZ, biology, medicine, biomedical research. 1. INTRODUCTION
Leonardo da Vinci was the first to use the principles and mechanisms of work and forms of animals in technology.
In the 1950s, the American biophysicist and polymath Otto Schmitt developed the concept of "biomimetics" (Bionics - Wikipedia material). The term "bionics" was coined by Jack E. Steele in August 1958 while working in the Aeronautics Division at Wright-Patterson Air Force Base in Dayton, Ohio , where Otto Schmitt also worked. Steele defined bionics as "the science of systems that have some function copied from nature, or that are characteristics of natural systems or their counterparts"
Bionics (from other Greek piov "living") is an applied science about the application of technical devices and systems of the principles of organization, properties, functions, and structures of living nature, that is, the forms of living things in nature and their industrial counterparts.
G. Altshuller in [1] proposed using the principles and mechanisms of the work of animals, especially ancient ones, for the development of technical systems.
The term Biomimicry has been around since 1982. Biomimicry was popularized by scientist and scientific author Janine Benyus in her 1997 book Biomimicry: Innovation Inspired by Nature... Benyus proposed to look at nature as a "Model, Criterion and Mentor" and emphasizes sustainabil-ity as a goal of biomimicry. Biomimetics could in principle, be applied in many areas. Due to the diversity and complexity of biological systems, the number of characteristics that can be imitated is large. Biomimetic applications are in various stages of development, from technologies that may become commercially viable to prototypes.
Today, the development of bionics (biomimetics) is going quite rapidly.
Burton's book Modeling and Differential Equations in Biology [2] describes how differential equation stability theory is used in modeling microbial competition, predator-prey systems, humoral immune response, and dose and cell cycle effects in radiotherapy, among other areas, which include population biology and mathematical ecology.
In mid-1976, V. Petrov conducted research on the possibility of transferring the laws of biology to create a system of laws for technology development. The results were reported at the TRIZ conference in Leningrad in 1977. Later, a book [3] was published based on these materials.
The papers [4] - [19] describe the application of TRIZ to biomimetics and the use of the Altshuller matrix for solving problems in this area.
The purpose of this article is to show a broader application of TRIZ tools in biomedical research. The authors will show this with various examples.
2. EXAMPLES OF THE USE OF TRIZ IN BIOMEDICAL RESEARCH
2.1. History of PCR development
A sample is taken for various DNA tests and for the diagnosis of diseases. However, there are cases when it is not possible to take a sample in the second time and this is the only material that can be used.
What to do?
The answer is obvious - we need to duplicate (amplify) DNA - this is done by using DNA replication (Replication (from lat. Replicatio - renewal) is the process of creating two DNA subsidiaries based on the parental DNA molecule. DNA replication is carried out by a complex, consisting of 15-20 different protein-garments, called a replica. With the help of special enzymes, the double spiral of maternal DNA is covered with two threads, the second thread is completed on each formed thread, forming two identical DNA molecules, which are then twisted into separate spirals. During the subsequent division of the mother cell, each subsidiary receives one copy of the DNA molecule, which is identical DNA to the original mother cell. This process provides accurate transmission of genetic information from generation to generation. The replica is a complex molecular machine that carries out DNA replication. The replica first spins a double-tension DNA into two single threads. For each of the obtained single threads, a new complementary DNA sequence is synthesized. The final result is the formation of two new dual-chain DNA sequences, which are accurate copies of the original dual-chain DNA sequence).
This was done for the first time by the Norwegian biochemist Kjell Kleppe in 1971. To do this, he used the enzyme DNA polymerase, which was first isolated in 1956 by the American scientist Arthur Kornberg from the bacterium Escherichia coli.
Some clarification needs to be made.
DNA exists in the form of a double helix, consisting of two separate DNA molecules.
Synthesis of DNA in a living cell is carried out by an enzyme - DNA polymerase, using small RNA molecules as a primer
In 1983, American biochemist Kary Mullis invented PCR and received US Patent 4,683,195 on July 28, 1987. For PCR reaction, before each new cycle of synthesis, a new portion of the enzyme DNA polymerase had to be added to the mixture, because it was quickly denatured due to the high temperatures used in PCR.
A new problem has arisen.
How to make DNA polymerase enzyme be more robust and work longer?
In such cases, TRIZ uses function-oriented search (FOP), which is a technology transfer.
Thus, you need to find an area where this function is performed in difficult conditions and massively. It means that you need to find the 'thermostable' DNA polymerase where it would work at high temperatures.
In 1985, Cary Mullis at Cetus Corporation began using thermostable Taq polymerase (isolated from the extremely thermophilic bacterium Thermus aquaticus) in PCR reactions, which greatly simplified the work. Taq polymerase was isolated in 1976 by US scientists Ellis Chien, David Edgar, and John Trela. This enzyme remained active even at temperatures above 75 °C.
В 1991 году ученые во главе с Эриком Матуром из биотехнологической компании Stratagene, (Калифорния), обнаружили ДНК-полимеразу Pfu (from Pyrococcus furiosus), которая демонстрирует значительно более высокую точность репликации, чем ДНК-полимераза Taq. In 1996, they received patents for exonuclease-deficient Pfu and for complete Pfu (U.S. Patent 5,489,523, U.S. Patent 5,545,552).
The advantages of Taq polymerase are its high speed of work (high processivity).
The disadvantage of this polymerase is the rather high probability of introducing an erroneous nucleotide, since this enzyme lacks error correction mechanisms (3'^5'-exonuclease activity).
The advantage of Pfu polymerase is a much more accurate copying of DNA molecules that significantly reduces the number of mutations in replicated DNA.
The disadvantage of Pfu polymerase is the low speed of polymerization (low processivity).
The contradiction of requirement 1 (CR - 1) for Taq polymerase is the high speed of their work (processivity), but the high probability of introducing an erroneous nucleotide (low proofreading activity).
CR - 2 Pfu polymerase has a low probability of introducing an erroneous nucleotide (high proof-reading activity), but has a low polymerization rate (processivity).
Property contradictions (PC -1). Why is Taq polymerase likely to introduce an erroneous nucleotide, since this enzyme lacks error correction mechanisms (3'^5'-exonuclease activity).
Ideal Final Result (IFR). High speed of work and high exact copying of DNA molecules.). High speed of work and high exact copying of DNA molecules.
The solution is hybridization. Using them together. Only advantages are remained while disadvantages are compensated.
2.2. PCR apparatus
The PCR apparatus should cycle through the following temperatures - 95, 55, 72 degrees Celsius.
The first PCR machines operated on the basis of heating with a thermal heating element, and cooling was carried out using a fan and air flow. PCR, especially for long DNA fragments, lasted 4-6 hours.
How to shorten the heating and cooling time?
As a solution to the problem, it was proposed to use the Peltier effect or the thermoelectric effect. A Peltier element was installed in the PCR apparatus, which quickly heated and cooled the reaction. It made possible to significantly shorten the process, and PCR reaction began to last 0.5-1.5 hours only, which furthermore made a revolution, especially in molecular diagnostics, particularly, in determining the presence of the coronavirus.
2.3. Quality and concentration of DNA and RNA
Spectrophotometry was used to check the concentration and quality of DNA and RNA (Spec-trophotometry - from Wikipedia). To do this, it was necessary to use special quartz cuvettes that let through and did not refract ultraviolet light (230-320 nm). Each quartz cuvette costs $100. It was
very expensive. In addition, a lot of scarce and expensive biomaterials were required to fill the cuvette. What can we do?
The contradiction of requirement (CR). Checking the concentration and quality of DNA and RNA requires an expensive cuvette and a large amount of biomaterial, which is not always available. . Those are a contradiction between the need to check and the high cost of the cuvette, and the amount of biomaterial.
Ideal Final Result (IFR). The check is carried out, the cuvette is cheap and the biomaterial costs are low.
Property contradictions (PC). To test, you need to use a large, expensive cuvette and a lot of biomaterials, and to reduce the cost of testing and to reduce the consumption of biomaterial, you need to have a small cuvette and a small amount of biomaterial. Let's allow PC in the structure.
Solution. They began to use quartz capillaries, which cost $1 only, as compared to $100 of a cuvette.
A new problem has arisen.
If it took a lot of checks and, accordingly, a lot of quartz capillaries were used. In addition, each test required a minimum of 5 microliters of biological material, which was not always available. Ideal Final Result (IFR). Do not use cuvette or capillary. Biomaterial is not overspent. Solution. Scientists began to use the technology of holding the sample, which uses only surface tension to hold the sample onto place. This eliminates the need for bulky and expensive cuvettes. A 1 |il sample is pipetted onto the end of the fiber optic cable (receiving fiber). The second fiber optic cable (source fiber) is then brought into contact with the liquid sample, causing the liquid to bridge the gap between the fiber ends. A flash xenon lamp serves as the light source and a spectrometer using a linear CCD array) is used to analyze the light after passing through the sample.
3. CONCLUSION
The article showed the possibility of using TRIZ tools for solving problems in biomedical research.
This approach allows not only a significant reducing the time for solving problems in biomedical research, but also to obtain qualitatively new results and predict new ways of biomedical research.
The authors tried to draw the attention of specialists in biomedical research and TRIZ specialists to further research in this area.
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