Team:Cornell/Business

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==Business Cost Analysis==
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=Business Case=
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In forming our business analysis, we consulted with Dr. Michael Shuler (Cornell University, Biomedical Engineering Department) and Dr. David Putnam (Cornell University, Biomedical Engineering Department).
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We have created a system in which products can be created continuously instead of large batches.  The following is an analysis of how our system matches up with current industrial standards.
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We have created a system in which products can be created continuously instead of in large batches.  The following is an analysis of how our system matches up with current industrial standards.
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===Capital Expenditure===
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==Capital Expenditure==
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Batch production processes has an advantage over our system in that it requires less capital and has a better economy of scale. Our system presents a linear economy of scale since to create more product, we need to run chips in parallel.  Batch production has a near-logarithmic economy of scale since producing each extra unit of product costs less up to a reasonable point.
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The batch production process has an advantage over our system in that it requires less capital and has a better economy of scale. Our system presents a linear economy of scale because we need to run chips in parallel to create more product.  Batch production has a near-logarithmic economy of scale, since scaling up production (by increasing the size of the batch and overall machine) costs less up to a reasonable level.
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===Operating Expenditure===
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==Operating Expenditure==
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Batch production has a lower cost of operation for relatively cheap bio-pharmaceuticals.  However, operating cost can climb steeply if the yield is lowered or quality is important.   
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Batch production has a lower cost of operation for relatively cheap bio-pharmaceuticals.  However, operating cost can climb steeply if the yield is low or quality is important.   
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For most expensive pharmaceuticals, a subset of the following factors generally will raise cost:
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For most expensive pharmaceuticals, some or all of the following factors have the potential to raise costs:
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# Presence of side reactions, where resources are used to produce unwanted byproducts instead of the target product.
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# Toxic intermediates, which can often kill the host cell before large yields of the target product can be reached. 
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# Pharmaceuticals are created intracellularly. In order to extract the products, companies must lyse cells and purify the products. About 50% of the cost of creating intracellular pharmaceuticals is in the cost of purification. There are often 5-7 steps required in purification to remove all cell lysate, including organelles, unwanted proteins, DNA, etc.
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# Quality factors, such as pH, temperature, concentration, etc., must be highly regulated.
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#*Different temperature, pH, etc. may be needed for different steps in the overall reaction.  For example, even if it is known that a pH of 5 optimizes the efficiency of the first step in a reaction, the optimal pH of the second step may not be the same. It is difficult to modulate the conditions within cells effectively, so optimal reaction conditions may not be achievable for every step in production.
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#*Quality factors must be at a very specific value.  Since mixing in a batch-processing does not perfectly homogenize the solution, there may be local variation in reaction conditions.
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<p>
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'''How our system addresses the challenges in batch processing:'''
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# Presence of side reactions, where resources are used to produce unwanted products instead of the target product.
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# In the cell, the formation of byproducts would reduce the yield of the target pharmaceutical. BioFactory limits side reactions by organizing enzymes linearly in the order required by the desired biochemical pathway. Thus, intermediates immediately encounter the correct enzyme, driving them towards the target product in isolation from cellular enzymes or molecules which could participate in side reactions.
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# Toxic intermediates can often kill the host cell.   
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# BioFactory is a cell-free systemTherefore, toxic intermediates in the biochemical pathway are no longer an inhibition to production.
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# Pharmaceuticals are created intracellularIn order to get the products, companies must lyse the cell and purify out the products.  About 50% of the cost of creating intracellular pharmaceuticals is in the cost of purification. There are often 5-7 steps required in purification to remove all cell lysate including organelles, other cell junk, other proteins, DNA, etc.
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# Purification steps in BioFactory would be significantly cheaper than those currently required by industry methodsWhile some purification steps may still be needed, as 100% yield is impossible, the cell-free method eliminates many steps in the purification process. The key potential for eliminating purification steps lies in the cell-free aspect of BioFactory; as the pathway's enzymes are extracted from the cell lysate via the streptavidin-biotin interaction, output from BioFactory would be free of cell components such as DNA or cell debris.
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# Quality factors, such as pH, temperature, concentration, etc., must be tightly controlled.  
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# A modular system allows for optimal reaction conditions at each step, because each step occurs in a different section of the system. In our system, each step would occur in a different microfluidic chip. This feature may enable our process to significantly increase yield as compared to the batch process system. Furthermore, our reaction mixture will be homogenous due to smaller volumes of reaction.
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#*Different factor values are needed for different parts of the overall reaction.  For example, if a pH of 5 is needed for the first step and then a pH of 8 is needed for the second step. Cells have a hard time with these reactions.
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</p>
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#*Quality factors must be at a very specific valueSince mixing in a batch-processing is not perfect and the solution is not completely homogenized, and often you get different values (of concentration, pH, etc.) at different locations.
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==Other Benefits==
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# Cheaper research and development stages for finding new pathwaysTesting new biochemical pathways using microfluidic devices instead of batch production means faster results and smaller volumes used, which will make R&D both faster and cheaper.
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# Highly exothermic reactions are safer in microfluidic devices since they dissipate heat more efficiently than batch processes.
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'''How our system solves the previously stated problems often found in batch processing:'''
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==Case Study==
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A particularly useful application of our system would be in the synthesis of 1,2-propanediol and 1,2,4-butanetriol. Both substances are incredibly useful in industry; 1,2-propanediol is used extensively in the pharmaceutical industry and 1,2,4-butanetriol is used in the production of jet fuels.
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# In the cell, a wide variety of enzymes can often contain pathways for the creation of other products that reduces the yield of the target pharmaceutical. We avoid side reactions because our system only includes the enzymes for a single biochemical pathway.
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There is strong interest in producing these chemicals through biological systems. However, bacterial production is hindered by side reactions and the accumulation of toxic secondary products. Our system’s linear and compartmentalized reaction pathway will limit these side products and reactions. Furthermore, since our manufacturing process is cell-free, unwanted toxic products will not affect the overall yield of useful product. This will allow for exceptionally efficient production of these chemicals [1,2,3].
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# Once the microfluidic chip is coated, there will be no need of cells.  Therefore, toxic intermediates in the biochemical pathway are not a factor.
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# Purification of our system would be much cheaper than what is used in industry. There will a some intermediates in our solution since we will not be able obtain 100% yield, but our method still eliminates most steps in the purification process.
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==References==
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#
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# Altaras NE, Cameron DC (1999) Metabolic engineering of a 1,2-propanediol pathway in Escherichia coli. Appl Environ Microbiol 65: 1180-1185.
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#*Our system allows us to have different quality factor values at each step, because each step occurs in a different microfluidic chip.  For example, we can have different pH or temperature in each chip. Therefore, in this scenario, our process would have much higher yield than the batch process.  
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# Altaras NE, Cameron DC (2000) Enhanced production of (R)-1,2-propanediol by metabolically engineered Escherichia coli. Biotechnol Prog 16: 940-946.  
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#*Since we have only a small volume of reactions at a given time, we have a more homogenized solution and can control quality factors much more closely than what can be done in large batches.
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# Altaras NE, Etzel MR, Cameron DC (2001) Conversion of sugars to 1,2-propanediol by Thermoanaerobacterium thermosaccharolyticum HG-8. Biotechnol Prog 17: 52-56.

Latest revision as of 04:18, 29 September 2011

Project Description | Future Directions | Business Development | Outreach/HP | Safety

Business Case

In forming our business analysis, we consulted with Dr. Michael Shuler (Cornell University, Biomedical Engineering Department) and Dr. David Putnam (Cornell University, Biomedical Engineering Department).

We have created a system in which products can be created continuously instead of in large batches. The following is an analysis of how our system matches up with current industrial standards.

Capital Expenditure

The batch production process has an advantage over our system in that it requires less capital and has a better economy of scale. Our system presents a linear economy of scale because we need to run chips in parallel to create more product. Batch production has a near-logarithmic economy of scale, since scaling up production (by increasing the size of the batch and overall machine) costs less up to a reasonable level.

Operating Expenditure

Batch production has a lower cost of operation for relatively cheap bio-pharmaceuticals. However, operating cost can climb steeply if the yield is low or quality is important. For most expensive pharmaceuticals, some or all of the following factors have the potential to raise costs:

  1. Presence of side reactions, where resources are used to produce unwanted byproducts instead of the target product.
  2. Toxic intermediates, which can often kill the host cell before large yields of the target product can be reached.
  3. Pharmaceuticals are created intracellularly. In order to extract the products, companies must lyse cells and purify the products. About 50% of the cost of creating intracellular pharmaceuticals is in the cost of purification. There are often 5-7 steps required in purification to remove all cell lysate, including organelles, unwanted proteins, DNA, etc.
  4. Quality factors, such as pH, temperature, concentration, etc., must be highly regulated.
    • Different temperature, pH, etc. may be needed for different steps in the overall reaction. For example, even if it is known that a pH of 5 optimizes the efficiency of the first step in a reaction, the optimal pH of the second step may not be the same. It is difficult to modulate the conditions within cells effectively, so optimal reaction conditions may not be achievable for every step in production.
    • Quality factors must be at a very specific value. Since mixing in a batch-processing does not perfectly homogenize the solution, there may be local variation in reaction conditions.

How our system addresses the challenges in batch processing:

  1. In the cell, the formation of byproducts would reduce the yield of the target pharmaceutical. BioFactory limits side reactions by organizing enzymes linearly in the order required by the desired biochemical pathway. Thus, intermediates immediately encounter the correct enzyme, driving them towards the target product in isolation from cellular enzymes or molecules which could participate in side reactions.
  2. BioFactory is a cell-free system. Therefore, toxic intermediates in the biochemical pathway are no longer an inhibition to production.
  3. Purification steps in BioFactory would be significantly cheaper than those currently required by industry methods. While some purification steps may still be needed, as 100% yield is impossible, the cell-free method eliminates many steps in the purification process. The key potential for eliminating purification steps lies in the cell-free aspect of BioFactory; as the pathway's enzymes are extracted from the cell lysate via the streptavidin-biotin interaction, output from BioFactory would be free of cell components such as DNA or cell debris.
  4. A modular system allows for optimal reaction conditions at each step, because each step occurs in a different section of the system. In our system, each step would occur in a different microfluidic chip. This feature may enable our process to significantly increase yield as compared to the batch process system. Furthermore, our reaction mixture will be homogenous due to smaller volumes of reaction.

Other Benefits

  1. Cheaper research and development stages for finding new pathways. Testing new biochemical pathways using microfluidic devices instead of batch production means faster results and smaller volumes used, which will make R&D both faster and cheaper.
  2. Highly exothermic reactions are safer in microfluidic devices since they dissipate heat more efficiently than batch processes.

Case Study

A particularly useful application of our system would be in the synthesis of 1,2-propanediol and 1,2,4-butanetriol. Both substances are incredibly useful in industry; 1,2-propanediol is used extensively in the pharmaceutical industry and 1,2,4-butanetriol is used in the production of jet fuels.

There is strong interest in producing these chemicals through biological systems. However, bacterial production is hindered by side reactions and the accumulation of toxic secondary products. Our system’s linear and compartmentalized reaction pathway will limit these side products and reactions. Furthermore, since our manufacturing process is cell-free, unwanted toxic products will not affect the overall yield of useful product. This will allow for exceptionally efficient production of these chemicals [1,2,3].

References

  1. Altaras NE, Cameron DC (1999) Metabolic engineering of a 1,2-propanediol pathway in Escherichia coli. Appl Environ Microbiol 65: 1180-1185.
  2. Altaras NE, Cameron DC (2000) Enhanced production of (R)-1,2-propanediol by metabolically engineered Escherichia coli. Biotechnol Prog 16: 940-946.
  3. Altaras NE, Etzel MR, Cameron DC (2001) Conversion of sugars to 1,2-propanediol by Thermoanaerobacterium thermosaccharolyticum HG-8. Biotechnol Prog 17: 52-56.