Using DoE in R&D Projects A Practical Case Study. Ron Stites Stites & Associates, LLC

Transcription

1 Using DoE in R&D Projects A Practical Case Study Ron Stites Stites & Associates, LLC

2 Ron Stites Former Director of Research for Range Fuels Three US Patents in Alternative Fuels Analytical Chemist -- BS Chemistry KU MBA Finance and Accounting Independent Consultant in Research Management Consulting Since LinkedIn: Ron Stites Blog: Main Lab: Brighton, CO, USA

3 Context Industrial R&D Questions are Fairly Well Defined Results Can be Translated into Financial Benefit An Application NOT Pure Science Cost Well Monitored Cost versus Financial Benefit a Frequent Discussion Generally in the Area of Sustaining Technology and not Disruptive Technology Evolutionary or Revolutionary For Society Success of Industrial R&D as Critical as Academic and Government Sponsored R&D

4 The Unique Nature of R&D Projects In General Many Unknowns Key Factors Key Results Causal Relationships Value of Solution Real Budget Real Time Line Real Goals Technical Programmatic It is often the Case that there is LESS Time and Money than Officially Budgeted

5 Where to Start? Problem/Opportunity Definition What is the Purpose of the Project? What does a Successful Project Look Like? What Factors are Important? What Results Need to be Measured? What is the Necessary Time-Line? What has been Done in the Past? Internal External Can We Put into Writing Something that Seems Do-able? Research Plan Project Charter/Plan This is an Intuitive Process that is Messy but MUST NOT be Skipped

6 What Next? Evaluate the Factors and Results Desired Do Measurement Techniques Exist? Do We Know the Ranges of Interest? Do We Know the Required Accuracy and Precision? Two Separate Questions Can We State Measureable ypotheses About the Relationships Between Factors and Results? Are We Ready for a DoE? What are the Gaps? In Many Cases the Answer is NO! Often New (or Modified) Measurement Techniques are Needed These Must be Developed and Tested Again in a more Intuitive Fashion

7 Guidance for Starting from Scratch Keep it Simple Keep it Cheap Avoid Going Directly to the Lab Go to the Library First Avoid Buying the Quantum Electromechanical Nuclear Pile to Measure p Use p Paper to Start Don t Spend More than about 25% of Budget on First Try Keep it Moving Forward Gets Bits of Knowledge at a Time Keep Trying Things and Taking Good Notes Keep Evaluating What are the Gaps? Be onest Even Cynical about what You KNOW

8 Case Study The Situation: Industrial Equipment Supplier Selling an Existing Devise into a New Market Corn Ethanol Not Much Known About Corn Ethanol Technology Devise is Known to Mix and eat Slurries Well Anecdotal Evidence that the Devise Improves Ethanol Yield Some Inconsistency in Data Art Expensive to Test at Plant ope to Learn ow the Devise Works to Improve Consistency of Performance

9 Preliminary Work Learn About Corn Ethanol Technology Starch to Glucose to Ethanol NOT Sugar Directly to Ethanol Key Opportunity is in Breakdown of Starch Key Gap is Measuring the Breakdown of Starch to Glucose Stepwise Starch to Maltodextrins Maltodextrins to Glucose

10 Many 1-4 α Glucoside Bonds ~O ~O O 4 O 6 4 C2O O O O 6 C2O O O O O O - 2O (Dehydration) O 4 6 C2O 4 6 C2O O O O O O Forming Long Chains Results in Starch Amylose in Particular (DP 300 to 3000) Only 1 Reducing End per Chain O

11 Additional 1-6 α Bond Branching ~O O 4 6 C2O ~O O O Yeast Cannot Digest These Macromolecules They Must be Broken Down at Least to Maltose but Much Preferred is Glucose 4 6 O O C2O O O (Dehydration) O O This Branching Results in Amylopectin another form of Starch (DP 2,000 to 200,000) O 4 6 C2O O O O~

12 Basic Process Grind Cook (~70C) React with Amylase and Glucoamylase Enzymes (~85C) Process More Complex Than Sugarcane Initial Cook is Called Slurrying olding at Temperature is Liquefaction Enzymes Present Throughout Distill Ferment (~32C)

13 What is the Opportunity? Speedup the ydrolysis Use Less Enzymes Minimize Burning of the Starch Shorter Chain Sugars Can React Together and with Proteins to Form Polymers that Yeast Cannot Digest Some are Even Toxic to Yeast Monitored by DP Analysis of the Maltodextrins But Measurement of Maltodextrins is Not Common New Methods are Needed Specialized Techniques are NOT Available in the Plant Samples Must be Sent to a Lab BUT WORSE Samples are NOT Stable ydrolysis Continues This Careful Thinking Resulted in a Very Specific R&D Project ow to Preserve Samples for Maltodextrin Analysis This Took Several Months to Accomplish

14 Clear Problem Definition Is There a Practical Way to Treat Samples to Stop the ydrolysis Reaction so that Samples Can be Shipped to a Lab for DP Analysis? What Methods are Practical? What Methods do not Change the DP Profile? What Lab Methods are Available and Practical? Internal? External?

15 Library Work Reviewed Published Literature on DP Analysis of Starch Considerable Work Done in Corn Ethanol Industry Much More Done in Starch Industry Contacted Plants Contacted Engineering Firms Contacted Analytical Suppliers Contacted Academic Researchers Contacted Enzyme Suppliers Found Clear Guidance on DP Analysis PLC Analysis Found A Number of Good ypotheses to Chase p & Temp Did NOT Find a Complete Testing Protocol Two Parallel Paths Develop PLC & Experimental Process

16 PLC Norm RID1 A, Refractive Index Signal ( \DP D) DP Corn Mash Slurried 0 rs DP DP DP DP DP DP DP DP min Norm RID1 A, Refractive Index Signal ( \DP D) DP5 Corn Mash Liquified 2.5 rs DP DP DP DP DP DP DP DP DP DP DP Glycerol min

17 Lab Liquefaction Difficult to Repeat Result Depends on: Time Temperature Mixing Water Content Needed a Consistent Starting Material to Measure Changes (Actually Lack of Change) Reliably Gave Up on Corn Too Difficult to Reproduce

18 Finally Worked Out a Surrogate Norm RID1 A, Refractive Index Signal ( \DP D) DP12+ 5% Maltodextrin Solution DP DP DP DP DP DP DP DP DP Purchased Maltodextrin Looked Much Like Corn Slurry Contained Large DP s and Some Small DP s Easy to Use and Control Took a Week to Work Out min

19 Protocol Development Make Up Consistent Maltodextrin Solution (10%) Add Controlled Amount of Enzyme Monitor %DP<9 as a Measure of Reaction Treat Some with 26% Sulfuric Acid (p s from 1 to 3) Treat Some with Cooling (0 and 25 C) Treat Some with Both old at a Typical Shipping Times (24 to 70 hr) Several Types of Tests were Run Over 2 Weeks Sort of Played Around to See What Made Sense

20 The Pay-Off After About 4 Weeks it Became Clear p Was the Most Important p of 2 Appeared to Work and Not Create Degradation of Sugars Temperature Might be Important Not as Clear Cut Not Sure About Time versus Temp Thought that holding at a higher temp for a few hours might help Maltodextrin Appeared to be a Useful Surrogate Reacted Rapidly with Enzyme Easy to Dissolve in Water at a Consistent Concentration (by Mass) The PLC Method Easily Detected Changes Changes in Smaller Sugars Concentrations (%</DP9) Easily Measured at Times and Temperatures of Interest We Seemed to ave Closed the Gaps Preventing a Useful DoE

21 The Actual DoE Factor 1 Factor 2 Factor 3 Response 1 Std Run A:p B:Incubate at 60C C:Store Temperature % <DP9 Units p C % No % Yes % No % Yes % Yes % No % No % Yes % After About 1 Week of Playing Around a Useful DoE was Actually Fairly Simple

22 Results Pretty Convincing Design-Expert Software Ln(% <DP9) alf-normal Plot Shapiro-Wilk test W-value = p-value = A: p B: Incubate at 60C C: Store Temperature Positive Effects Negative Effects Most Important Factor is A = p Incubation Slightly Worse alf-normal % Probability A 0 We Chose the ln Transformation because it Worked Well for Other Reaction Rate Experiments Slight Improvement ere Standardized Effect FIGURE XI ALF NORMAL PLOT OF ln TRANSFORMED DATA

23 Additional Evaluation Design-Expert Software Ln(% <DP9) A: p B: Incubate at 60C C: Store Temperature Positive Effects Negative Effects A Pareto Chart t-value of Effect Bonferroni Limit t-value Limit Rank FIGURE XII PARETO CART OF EFFECTS Adjusting p as Profound Effect As Expected

24 Does It Preserve? Sample %<DP9 %Delta Notes SX % Mother Liquor SX % 0.28% p 2, No Incubation, Store 3C SX % % p 2, Incubate, Store 25C SX % % p 2, Incubate, Store 3C SX % % p 2, No Incubation, Store 25C Only p Adjustment and Storage at 3C has Change Less Than the Standard Deviation of the PLC Method (~1%) Since These are Practical Things to Do in the Field, This was the Method Selected Took About 6 Weeks

25 Epilog Method Implemented Seemed to Work for Slurries and Liquefacts Some Strange Results with Fermentation Samples Most of the Carbohydrates Gone Discovered that the SO4(-2) was Interfering with the DP12+ Peak Throwing Off Calculations Method Modified to Remove SO4(-2) by Treatment with Ba(O)2 and Filtering Now Seems to Work Well with Ferms Also Always Remain Skeptical and Vigilent Especially When Applying to Other Conditions and Samples

26 Questions?

27 Stites Awarded Patents US Patent 7,884,253 B2, 2/8/2011; Methods And Apparatus For Selectively Producing Ethanol From Synthesis Gas; Stites and ohman. US Patent 7,919,070 B2, Apr. 5, 2011; Multi-Zone Reforming Methods and Apparatus for Conversion of Devolatilized Biomass to Syngas; Stites, Biehle, Klepper and Ridley. US Patent 8,142,530 B2, Mar. 27, 2012; Methods and Apparatus for Producing Syngas and Alcohols; Klepper, Geerstsema, Tirmizi, Robota and Stites. Additional Patents in Various Stages of Application/Approval

28 PLC Trace versus Time Malto-Dextrins (SX19) 32C p Time 0 Time 0.5 Time 1.5 Time 2.0 Time 4.0 Time 22 Time DP12+ DP11 DP10 DP9 DP8 DP7 DP6 DP5 DP4 DP3 DP2 DP1

29 Results Pretty Convincing Design-Expert Software Ln(% <DP9) Lambda Current = 0 Best = Low C.I. = igh C.I. = 1.27 Recommend transform: None (Lambda = 1) Box-Cox Plot for Power Transforms Ln(ResidualSS) We Chose the ln Transformation because it Worked Well for Other Reaction Rate Experiments Not Really Needed ere Lambda FIGURE XI ALF NORMAL PLOT OF ln TRANSFORMED DATA