Sterilization Device for Liquid Sterilization Device for Liquid Chromatography SolventsChromatography Solvents
Design TeamDesign TeamNick Roulleau, Michael VoseNick Roulleau, Michael Vose
Michael Racette, Michael McKayMichael Racette, Michael McKay
AdvisorAdvisorProfessor Mohammad TaslimProfessor Mohammad Taslim
Introduction Introduction
• Background Background
• Problem StatementProblem Statement
• Past ArtPast Art
• Design RequirementsDesign Requirements
• Design ConceptsDesign Concepts
• Prototype DesignPrototype Design
• Component AnalysisComponent Analysis
• RecommendationsRecommendations
What is Liquid Chromatography?What is Liquid Chromatography?
A substance comprised of components A and B is dissolved A substance comprised of components A and B is dissolved in a solvent and enters the analytical column, where it is in a solvent and enters the analytical column, where it is separatedseparated
Basic Components of an HPLC SystemBasic Components of an HPLC System
From http://www.waters.com/WatersDivisionFrom http://www.waters.com/WatersDivision
ProblemProblem
From http://www.waters.com/WatersDivisionFrom http://www.waters.com/WatersDivision
Design GoalDesign Goal
To mitigate the risk of blockage at the To mitigate the risk of blockage at the inlet frit due to bacterial contamination inlet frit due to bacterial contamination and extend the useful life of the UPLC and extend the useful life of the UPLC column.column.
Existing SolutionsExisting Solutions
• In-line filtersIn-line filters
• Guard columns and cartridgesGuard columns and cartridges
• Pre-filtration of samples and Pre-filtration of samples and mobile phase liquidsmobile phase liquids
Product RequirementsProduct Requirements• Mandatory:Mandatory:
» Must be adaptable for use worldwideMust be adaptable for use worldwide» Must extend the useful life of columnsMust extend the useful life of columns» Must meet safety standards (ISO, UL and CE)Must meet safety standards (ISO, UL and CE)» Must operate for 1 year w/o user interventionMust operate for 1 year w/o user intervention
• Desirable:Desirable:» Should be able to filter two bottles simultaneouslyShould be able to filter two bottles simultaneously» Should meet customer acceptance criteriaShould meet customer acceptance criteria
– Low-maintenanceLow-maintenance
– Easy to use Easy to use
– CostCost
ConstraintsConstraints
• Cannot change the chemical compositionCannot change the chemical composition» Of the solventOf the solvent» Of the sampleOf the sample
• Cannot create risk of causing pump cavitationCannot create risk of causing pump cavitation
• Cannot hinder bottle accessibilityCannot hinder bottle accessibility
• Cannot negatively impact system resolutionCannot negatively impact system resolution
Initial Design ConceptsInitial Design ConceptsUV Probe
Pump/filter--External enclosure
Pump/filter--Cap enclosure
Preliminary Design – UV ProbePreliminary Design – UV Probe
• InexpensiveInexpensive
• Simple DesignSimple Design
Why Not Use Ultraviolet Radiation as a Why Not Use Ultraviolet Radiation as a Primary Solution?Primary Solution?
• Degradation of organic solvent modifiers Degradation of organic solvent modifiers (Low Risk)(Low Risk)
• Degradation of aqueous additives Degradation of aqueous additives (Low Risk)(Low Risk)
• User safety from UV-C exposure User safety from UV-C exposure (Medium Risk)(Medium Risk)
• UV can inactivate but not remove UV can inactivate but not remove bacteriabacteria
• How many bacteria could be generated per year?How many bacteria could be generated per year?
• Logarithmic growth: Logarithmic growth: » Assuming worst caseAssuming worst case
– 100% replicating100% replicating– Short generation timeShort generation time– Neglecting lag phases and cell deathNeglecting lag phases and cell death
• Filter capacity = 10Filter capacity = 107 7 CFU/cmCFU/cm22
Filter SizingFilter Sizing
Filter SizingFilter Sizing
With logarithmic bacterial growth, filter area With logarithmic bacterial growth, filter area becomes exceptionally large in a short period becomes exceptionally large in a short period
Current DesignCurrent DesignExternal Filter Enclosure with UVExternal Filter Enclosure with UV
Dual-head Dual-head
brushless DC brushless DC
pumppump
UV lamp UV lamp
with multiple with multiple
sterilization sterilization
lineslines
Pall AcroPak 200 filtersPall AcroPak 200 filters
Filter SelectionFilter Selection
• Membrane with material Membrane with material compatibilitycompatibility
• Sufficient capacity to contain 1 Sufficient capacity to contain 1 year of inactivated bacteria year of inactivated bacteria
Pump SelectionPump Selection
Micro-diaphragm pumpMicro-diaphragm pump
• Dual pump headsDual pump heads
• Ability to run dryAbility to run dry
• DC brushless motor for DC brushless motor for long lifelong life
Pump Pressure RequirementsPump Pressure Requirements
• Pump must deliver sufficient differential pressure (Δp) to move fluid through filter
• Darcy’s equation for porous media:
)(
)( 21
L
ppkAQ
Q = flow ratek = permeability constant for filterA = effective filter area (EFA)µ = viscosity
L = membrane thicknessp1 = pump-side pressurep2 = outlet pressure
UV Block Design-Initial ConceptUV Block Design-Initial Concept
UV Block DesignUV Block Design
• 99.99% inactivation requires a UV dose of at least 40 mJ/cm2 for nearly all species of bacteria
• Dose is a function of the irradiance (mW/cm2) and time of exposure (in seconds)
Dose = Irradiance x timeDose = Irradiance x time
1
1tan
1
)1(
)1(tan
2
1tan
1 11
2
121 H
H
HHY
HX
XYH
HXL
H
L
HFd
r
lL
r
hH
22)1( LHX 22)1( LHY
dA
A
UV Block DesignUV Block Design
UV Block DesignUV Block Design
13 loops necessary with an 18W UV bulb and thin wall FEP tubing13 loops necessary with an 18W UV bulb and thin wall FEP tubing
Test PlanningTest Planning
• Verification TestVerification Test
» Does the Device Meet Does the Device Meet Design Requirement?Design Requirement?
» Pump Particle-Laden Pump Particle-Laden Water from Bottles With Water from Bottles With and Without Device and Without Device
» Compare Backpressure Compare Backpressure and/or Flow Rate and/or Flow Rate
PRESSURE
0
10
20
30
40
50
60
70
80
0 100 200 300
PumpPumpDeviceDevice SensorSensor
ColumnColumn
Test ResultsTest ResultsBackpressure Test
0
2
4
6
8
10
12
1 599 1197 1795 2393 2991 3589 4187 4785 5383 5981 6579 7177 7775 8373 8971 9569 10167 10765 11363 11961
Elapsed Time (s)
Ba
ck
pre
ss
ure
(P
SI)
No Device
Device (Norm)
Backpressure was reduced by 28% when our device was usedBackpressure was reduced by 28% when our device was used
Cost AnalysisCost Analysis
• Developed target costs by estimating: Developed target costs by estimating: » Annual costs without the assistance of our device Annual costs without the assistance of our device
(excluding operational costs)(excluding operational costs)
» Savings in material costs by implementing our deviceSavings in material costs by implementing our device
• Potential savings for high-end users = $44,000Potential savings for high-end users = $44,000
• Minimum estimated annual savings = $600Minimum estimated annual savings = $600
• Target production cost = $500Target production cost = $500
• Target prototyping cost = <$1500Target prototyping cost = <$1500
Recommendations for Further Recommendations for Further DevelopmentDevelopment
• Improve manufacturability of the designImprove manufacturability of the design» Simplify tubing systemSimplify tubing system» Smaller pumpSmaller pump» Custom filter sizeCustom filter size
• Analyze effectiveness of UV with Analyze effectiveness of UV with microbiological testingmicrobiological testing
SummarySummary
• Introduction to liquid chromatographyIntroduction to liquid chromatography
• The problem and its sourceThe problem and its source
• Requirements of a good solutionRequirements of a good solution
• Design considerationsDesign considerations
• Prototype design and analysisPrototype design and analysis
• RecommendationsRecommendations
Questions???Questions???