TRIZ APPLICATION IN BIOTECH – MOLECULAR GENETICS

( Part 1 of 2 – continue in August eScope) 

By: Akhilesh Gulati

 

It had been a while since the Executive Council talked about Structured Systematic Innovation with TRIZ.  Collectively they had agreed to move on to other areas of interest, what with the rapidly changing marketplace, new technologies and awareness of social responsibility.  In the meantime, though, members had been trying to incorporate different aspects of TRIZ.  Some had started exploring advanced concepts within TRIZ, expanding their knowledge and understanding.  Others had stuck to the basics; often consulting with Henrietta to help them clarify their understanding as they struggled with other problems.  Yet others had been talking to people in different industries.

After a hiatus of almost a year, the council members decided it was time to share some of their experiences and learning since then.  Mike, who had recently moved to an academic environment, said that he shared the council’s TRIZ stories with some faculty and research students at the Dept. of Applied Sciences.   At one of their speaker series they had people from the pharmaceutical, medical devices and the life sciences industry.  Mike remembered the pharmaceutical examples from their council meeting a year or so ago and shared it with Erika, one of the attendees.  Interestingly, Erika responded that her Applied Life Sciences group had been having a challenging time with some analysis and they tried to use TRIZ.  She said something about PCR application for the detection of mutations in DNA.

“You know,” Mike continued, “I am not a technical person and all talk of DNA goes well over my head.  But I was drawn to Erika because she mentioned the Contradiction matrix and how her team applied it to generate solutions to their PCR challenge.  My ears became really attuned to her when she referred to the Contradiction Matrix along with the 40 Inventive Principles as the simplest instrument of TRIZ toolkit.”

Apparently she went on give him a quick synopsis of what they did, and all he could say was that he was impressed and invited her to share their application story with the group.  Mike had discussed this with the council’s facilitator, Belinda, and scheduled Erika to share the story, although in ‘layman’ terms, at least where the technical jargon was concerned.  With this, Mike introduced Erika to the council members and sat down.

Erika thanked Mike and the group for inviting her, happy to be sharing her experience.   She said, “Let me start by explaining PCR in layman terms.  PCR stands for Polymerase chain reaction.  It is a way to make many copies of a sequence of DNA.  We do this in a lab, using an enzyme called DNA polymerase.  We call this a chain reaction because the result of one cycle is used immediately for the next cycle. This allows exponential growth to happen.”

Josh, always the questioning and curious member of the council, always looking at the practical side of things, raised his hand with a question, “Why do we want to do that? Does this copying of DNA not create mutations that can be harmful?  Perhaps creating Frankenstein?”  There was a bit of a glee in his eyes as he said Frankenstein, lending a bit of levity to the session.

Erika smiled, “PCR has many uses in a biological or biochemical setting.  As you have all probably heard or read, DNA is unique for every living thing.  As experimenters we can often extract only small amounts of the DNA from a specimen.  Since these amounts are usually too little to be useful, scientists use PCR to make enough copies to start experimenting with.  For this reason, PCR is one of the most common techniques used in genetics labs around the world, making it useful in experiments on many things, including gene therapy, infectious diseases, and even forensics.  Now that might be of interest to those of you who watch the crime investigation shows on TV.  I certainly hope that we do not create Frankenstein with our lessons learned!”

The PCR method consists of repeated heating and cooling, causing “melting” or “separation” of the two strands and replication of the original DNA.

“We do this in three steps:

  1. Denaturation — Heating the sample to separate the strands
  2. Annealing — Cooling the sample to allow the primers to bind the to ends
  3. Extension — DNA polymerase attaches to the primers and makes a copy of each template strand. Attaching of the DNA polymerase to the ends to make a copy of each of the original DNA samples

I know this sounds complicated. Anyway, after the first cycle, there are 4 DNA strands. The process repeats with the 4 DNA strands, which will go on to make 8 strands, then repeat itself again to make 16 strands. In this way, PCR doubles the amount of DNA in a sample after each cycle, making it possible to make millions of copies of a DNA strand quickly.  These we then use for analysis.

Without getting into any further jargon, this is the basic process.”

Erika went on to explain how her team was using CADMA, a modified form of PCR.   Seeing how this was getting more technical than this forum or the time allowed, she decided to get to the issue they were having.  Her team was encountering difficulty in simultaneous analysis of several targets using multiple DNA samples in a single thermocycler.  They were unable to achieve satisfactory results by standardizing the quantity of template DNA, by adjusting the primer concentration and even the annealing temperature and buffers.  Since brainstorming had so far failed to get them to satisfactory solutions, they decided to opt for the more systematic TRIZ methodology.

“A year ago, our Director of Quality had approached us to consider TRIZ methodology for our research, but we were not exactly open to it, especially since it has not been systematically applied to address challenges in molecular genetics!  Now we thought it would be a good test of this methodology.   This being our first time with TRIZ, we wanted to stay with the simplest TRIZ method, the 39×39 Contradiction Matrix and 40 Inventive Principles.

“We started by first formalizing the problem: Optimize Reactions for multiple targets in CADMA PCR.

Next, we set to identifying our technical contradictions:

We wanted to obtain an unambiguous signal for two different types of templates with similar fluorescence intensity for each of the genetic targets.  I can see the bewildered look on your faces. Let me try to explain.  Remember I said that we create copies of the DNA strands.  Well, once the reaction is complete, it is tested on an electrophoretic gel where the fluorescent signal of copied DNA is checked for confirmation. If the PCR cycling conditions are not suitable for the above process to take place, there may be extra or absent fluorescent bands that interfere with accurate interpretation of the results. This is an ambiguous result.  This makes it difficult to accurately interpret and form conclusions.  We need an unambiguous signal if we want reliable results.

To be continued ………

 

Ref: This article is based on a paper “Surmounting a PCR challenge using a Contradictory matrix from TRIZ” by Jiri Drabek, Molecular Geneticist at IMTM.

About: Akhilesh Gulati

Akhilesh Gulati is a Principal of Pivot Management Consultants helping companies implement change strategies through Lean, Six Sigma and TRIZ.  He was also the CEO of PivotAdapt, a Data Analytics company that he rolled into Pivot Management Consultants.  He has over 25 years of experience in operations and process improvement, design, lean, Six Sigma, strategic planning, and TRIZ (structured innovation) training and consulting.

Akhilesh has been active with ASQ for over 25 years, is a past chair of Section 702 and most of us know him through his presentations to our Section and his Radical Thinking articles.  Akhilesh holds M.S. in Naval Architecture and Marine Engineering from the University of Michigan, Ann Arbor, and an MBA from UCLA.

 Learn more about Akhilesh Gulati at www.pivotmc.com