ASM Competition UTArlington Entry 2011

7/30/2019 ASM Competition UTArlington Entry 2011

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BOX 19031, 500 W. FIRST ST., 325 WOOLF HALL, ARLINGTON, TEXAS 76019-0031T 817-272-2398 F 817-272-2538 http://www.uta.edu

THE UNIVERSITY OF TEXAS AT ARLINGTON

MATERIALS SCIENCE AND ENGINEERING

06-13-2011

Ms. Jeane Deatherage

Administrator, Foundation Programs

Materials Park, OH 44073

RE: Undergraduate Design CompetitionDear Jeane:

I am pleased to inform you that the Undergraduate Design Competition Submission

entitled Controlled Release Drug Delivery System by Letia Blanco, ChristopherAlberts, Kyle Godfrey, Andrew Patin and Chris Grace is the only one from the Materials

Advantage-University of Texas at Arlington Chapter. The students have committed to

make sure that in the event that they win the competition at least one of them will come

to the MS&T meeting this fall. If you have any questions please do not hesitate to contact

me. Best wishes.

Sincerely yours,

Pranesh B. Aswath Ph.D.

Professor and Associate Chair

Faculty Advisor: Materials Advantage-University of Texas at Arlington

Materials Science and Engineering Department

University of Texas at Arlington

Arlington, TX 76019

817-272-7108

[email protected]


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eam Members

2011

Team Members

Letia Blanco

Christopher Bryan Alberts

Kyle Godfrey

Andrew Patin

Chris Grace

Advisors

Dr. Shiakolas

Dr. Aswath Correspondence Address

2620 Bauer Drive

Denton TX 76207


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Table of Contents

Executive Summary 1

Report Body

Introduction 1

Device Design 3

Analytical Thermal Model 13

ANSYS IcePak Finite Element Model 19

Release Rate Testing 23

Project Conclusions and Recommendations for Future Projects 27

Appendices

Appendix A: Fabrication Processes

Appendix B: Bibliography

Appendix C: Dimensioned Drawings

Appendix D: Material Data Sheets


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Executive Summary

Half a million people in America seek medical treatment for burns every year and for

40,000 of them, their injuries are severe enough to require hospitalization. Treatment of thesevery painful injuries consists of applying multiple topical medications to fight bacterial infection,keep the wound moist, reduce pain and stimulate tissue growth. This often requires that thewound dressing be opened multiple times a day. This process is extremely uncomfortable for thepatient and it exposes the wound to the environment, significantly increasing the chance ofinfection. If a system could be designed to increase the amount of time between dressingchanges, both pain and the likelihood of infection could be reduced.

The Controlled Release Drug Delivery Device is specifically designed to increase theamount of time between wound dressing changes. This goal is accomplished through theimplementation of two key concepts. We use a hydrogel that can be both hydrophilic andhydrophobic depending on its temperature, by controlling the temperature of the hydrogel using

thermoelectric devices we are able to both heat and cool the hydrogel when necessary, ensuringexcellent temperature control and thus controlled drug delivery. Our bandage consists of manyseparate modules capable of distributing multiply medication all on their own time schedule.These modules are connected by a flexible plastic allowing the bandage to comfortably conformto any wound. A lateral wiring scheme allows for bandage size customizability and removablemedicine trays allows spent hydrogel to be removed and the electrical components sterilized,then recharged and reused.

We have created a device that offers controlled delivery of multiple medications withoutthe removal of wound dressings. We believe this device will be a profitable product that willreduce infections, diminish patient discomfort, shorten hospital stays, lessen medical costs andsave lives.

Introduction

Background and Motivation

Every year approximately 500,000 Americansreceive treatment for burn related injuries. 40,000Americans require hospitalization and 24,000 requiretreatment at specialized burn care facilities (AmericanBurn Association). For the vast majority of theseindividuals a long and painful process is required for thetreatment and healing of the wounded areas.

The wound site is very sensitive to any amountof stimulation. This means that every time the wound isinspected and subsequently dressed, the patient must

endure a large amount of pain. Since dressing changes Figure 1 - Example of Wound, AppropriateApplication for our Bandage


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must be made on a very regular basis, every 8-12 hours, the treatment process becomes a never-ending struggle with pain.

The second problem in burn wound treatment is the risk of bacterial infection. Onaverage bacterial infection accounts for between 50-60% of all deaths in burn patients (SallyAbston MD). Bacterial infection is often prevalent in burn victims due to a combination of dead

tissue, a weakened immune system and the destruction of the skin's barrier to infection. Thisallows bacteria to penetrate deep into the skin and permits travel through the lymph system.Physicians are forced to inspect the wound site on a regular basis to ensure that burn wounds arenot becoming infected. Repeated wound inspection exposes the wound site to potential infectioncausing contaminants.

Along with painful treatment, burn victims must also deal with large financial burden. In1992, a burn that covered 30% of the victims body could cost around two hundred thousanddollars to treat. The average cost of burn related hospitalization was $17,300 versus $9,000 forall other types of stays. The average hospital stay for burn patients was 8.9 days versus 5.1 daysfor all other types of patients (United States Department of Labor). If we can create a device thatcan improve the effectiveness of burn treatment, we can save lives, lessen suffering, shorten

hospital stays and save money.

A New Approach

The MicroMed Controlled Release Drug Delivery Devise has been designed to be a newapproach to burn wound and skin graft donor site management. With this device the patient willexperience a much less traumatic rehabilitation process due to a reduced amount of pain duringtreatment as well as a reduced likelihood of infection. The devise accomplishes this task byallowing a longer period of time to pass betweendressing changes.

The MicroMed Controlled Release DrugDelivery Devise is a drug release mechanism whichoffers the medical practitioner complete control overthe drug time rate of release. It is a modular devicewhich can be custom sized for individual burn woundneeds. It consists of individual modules that areloaded with medications to treat the wound. ReferFigure 2 Drug Delivery Device. Each module allowsthe operator to choose exactly when, how long and at

what intensity the drug is released. When the modulehas delivered its entire drug supply it can be reloaded

with a fresh supply of drugs.The MicroMed Controlled Release Drug Delivery Device is a significant breakthrough in

the way burn wounds and skin graft donor sites could be treated. By allowing physicians toeffectively treat wounds in a much less invasive way this devise promises to reduce pain andinfection and give patients higher levels of comfort during treatment than they have ever hadbefore.

Figure 2 Drug Delivery Device


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Device Design

The purpose of our design is to produce a flexible bandage that can release multiple medicationson any time schedule determined by a doctor. Figure 3 Bandage Visualizing Multiple

Medication Placement and Release Control, imagine the blue modules could be releasing anantimicrobial every hour, the yellow modules a growth hormone every four hours and the greenmodules could be releasing a pain killer continuously. In general,we determined that any good design would need to:

1. Allow for significant customizability, both in the shapeand size of the bandage and the specific configuration of

medication within the device

2. Be easy to manufacture by minimizing the number andcomplexity of individual parts while incorporating

available materials and off the shelf parts

3. Be robust enough to survive transport and use4. Be comfortable for the patient and easy to use

Thermally Responsive Hydrogel

The fundamental building block of our design is a thermally responsive composite hydrogel.This Composite Hydrogel consists offour parts:

Thermally responsive polymer Therapeutic nanoparticles Photo-initiator Irgacure 2959 Matrix polymer

Poly[N-isopropylacrylamide-co-acrylamide] PNIPAM-AAm) is ourthermally responsive polymer, it canbe loaded with drugs and experiences aphase change at a lower criticalsolution temperature (LCST). Below theLCST the PNIPAM-AAm is hydrophilic,allowing it to be loaded with an aqueous solution containing therapeutic nanoparticles. In ourdevice this could be antimicrobial agents, analgesics or growth hormones for wound treatment.When exposed to temperatures above the LCST, the PNIPAM-AAm becomes hydrophobic andrejects the aqueous solution of medication into the surrounding hydrogel at which time themedicine travels by diffusion to the wound site. The acrylamide was added to increase the LCSTfrom about 80 F to about 100 F, thus ensuring that normal contact with skin would not beenough to activate the medication release. The temperature sensitive polymer, PNIPAM-AAm, isimpregnated with medicine and is then mixed with a photo-initiator, Irgacure 2959, and a matrix

Figure 4 Description of Thermally Responsive Composite Hydrogel (Sabnis)

Figure 3 Bandage Visualizing Multiple Medication

Placement and Release Control


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polymer. Poly[ethylene glycol] diacrylate (PEGDA) was chosen as the matrix polymer for itscross linking abilities. Next, this mixture isexposed to UV light, resulting in a gelatinoussubstance subsequently referred to as theComposite Hydrogel. Please see Figure 4

Description of Thermally ResponsiveComposite Hydrogel (Sabnis). For moreinformation on the fabrication of thehydrogel please see Appendix A: FabricationProcesses.

When held continuously at a temperatureabove the LCST, the therapeuticnanoparticles experience three types ofrelease phases. The Initial Burst Phase,

usually completed in the first hour, is the highest rate of release. The second phase, Sustained

Burst, lasts usually 1-8 hours and is significantly slower than the Initial Burst release. The lastphase is the Plateau Release phase, which is a period of very small but still continuing release.Please see Figure 5 Example Graph of Drug Release Rates (Sabnis). By instead exposing thehydrogel to cycles of heating and cooling, we minimize the amount of medication releasedduring the burst phase, thus enabling uniform doses.

Hydrogel Containment Chamber

In order to enable individual control, about .062 cm3 of Composite Hydrogel is held in separatecontainment chambers, each tray containing a single medication.. Stainless Steel was chosen asthe chamber material due to its excellent thermal conductivity, its biocompatibility, its ability to

be sterilized and its established ubiquity in medical devices. (Note: due to material availability,containment chambers in the proof of conceptprototype were made from Aluminum.) Holdingthe hydrogel in a container that can be removedfrom the overall device allows us to easily photo-polymerize the Composite Hydrogel directly in thetray, ensuring repeatable shape and volume. In trayphotopolymerization also results in a small amountof adherence between the hydro gel and the wallsof the tray, helping to prevent the hydrogel fromshifting within the device. These removable trayscould allow the doctor to easily recharge theirbandage with disposable medicine trays whileallowing the more expensive electrical componentsto be sterilized and reused. For more informationon tray fabrication, please see Appendix A:Fabrication Processes. For a dimensioned drawingof the tray, please see Appendix D: Dimensioned Drawings.

Figure 5 Example Graph of Drug Release Rates (Sabnis)

Figure 6 - Tray with Composite Hydrogel


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Temperature Regulation using Thermoelectric Devices

To control the release of the medication, we must be able to control the temperature of thehydrogel. Each tray containing Composite Hydrogel is heated to release temperatures by contactwith a thermoelectric device (TED). Thermoelectric devices take advantage of the Peltier effect

to move heat both with, and more importantly against a temperature gradient. N-type and P-typesemiconductors are wired in series and sandwiched between two ceramic plates. Due to theirsolid-state construction, thermoelectric devices are dependable. They are also available in verysmall sizes and they have sufficient heating and cooling capabilities. Thus, each cavity ofComposite can be controlled individually. Thermoelectric devices act as reversible heat pumps.

If current is passed through the thermoelectric in one direction, the thermoelectric will functionas a heater see Figure 7Thermoelectric Device as a Heater. If current is passed through thethermoelectric in the opposite direction, it will function as a cooler; see Figure 8 -Thermoelectric Device as a Cooler. For more information about the thermoelectric device wehave chosen, see Appendix C: Material Data Sheets.

Alignment Structure

Each thermoelectric device and tray of hydrogel fits into a poly(methyl methacrylite) or PMMA

insert. This insert provides rigidity while ensuring that the thermoelectric and the tray ofhydrogel remain properly aligned during use. The sub-assembly the tray of Composite Hydrogelin contact with the thermocouple and the TED, all inside the PMMA insert will subsequently bereferred to as a Module. For an exploded view, please see Figure 8 - Module Exploded View. Foran assembled view, please see Figure 7 - Module Collapsed View. For a photo of a fabricatedmodule please see Figure 9 - Completed Module. For the manufacturing processes used in thefabrication of the PMMA insert, please see Appendix A. For more information on PMMA,

Figure 7 Thermoelectric Device as a Heater Figure 8 - Thermoelectric Device as a Cooler


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please see the Material Data Sheet in Appendix C. For an engineering drawing of the PMMAinsert, please see Appendix D.

Connecting the Modules

Each individually controlled module fits into a cavity of a housing made frompolydimethylsiloxane (PDMS). This strong, flexible material is common in biomedicalapplications. Connecting the rigid modules with this flexible material reduces the rigid footprint

of the device allowing thebandage to conform to thewound. This separation betweenmodules also reduces heat

bleeding between cavities,allowing each module to heat andcool properly no matter thetemperature of the surroundingmodules. For information aboutPDMS, see its Material DataSheet in Appendix C. For thefabrication process, please see

Figure 11 - Lateral Wiring

SchemeFigure 10 - Variable Length Bandage

Figure 8 - Module Exploded View

Figure 7 - Module Collapsed View

Figure 9 - Completed Module


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Appendix A. For an engineering drawing of the PDMS Casing please see Appendix D. Eachmodule will be wired laterally into strips several modules long. Each of these strips would beindependently wired so the bandage could be cut in between strips without compromising theintegrity of the wiring. The width of thebandage is fixed by the number of modules in

a strip, but the length of the bandage iscustomizable to the size of the treatment site.See Figure 10 - Variable Length Bandage andFigure 11 - Lateral Wiring Scheme. Eachmodule has the wires from the thermocoupleand the wires to the thermoelectric each willmeet at a connection pin that will plug into avariable length wiring harness that willconnect to a battery operated portablecontroller. Thus, this bandage could work inany situation from the hospital setting to a

soldier in the field.

Closed Loop Control System

Figure 13 - Control Diagram

SBC -68 Connecting Block

3 IC H-Bridges

3 Devices

12V Power Supply

Figure 12 - PDMS Casing with Single Module


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Our control system hardwarde includes a 12V power supply capable of delivering 4A, an IC H-bridge to allow for current switching and voltage control, thermocouples to read the temperatureand a National Instruments SCB-68 connecting block to allow for wire connection to the NI PCI-6221 DAQ card installed in a Dell Optiplex 745 PC running Windows XP SP3 with LabVIEW2010.

One 40 gauge K Type bi-metallic thermocouple is inserted in between the thermoelectric deviceand the tray of hydrogel and held in place by thermal epoxy. Another thermocouple is inserteddirectly into the tray of hydrogel. First the thermocouple feeds back the voltage, which isconverted to a temperature via a calibration curve. The raw thermocouple data was thencompressed at a rate of twenty to one, reducing the number of data points being recorded. Thecompressed signals were then linked to a graph in order to monitor the temperatures. In additionto a graph the data is written to an excel file to monitor the temperature history of each moduleduring testing. If the temperature is outside the desired range, LabVIEW will send the signal toan IC H-bridge which changes the direction of current flow through the thermoelectric deviceenabling heating or cooling.

The IC H-bridge has two inputs to control itsbehavior. The first input, on pin 3, controlswhether the H-bridge passes current in onedirection (5V applied by LabVIEW), or theother direction (0V applied by LabVIEW);this current direction switching is whatallows the user to select heating or coolingvia the computer. The second input, on pin4, controls whether the H-bridge is allowing

current to pass or not; this on / off capabilityacts as a relay allowing us to electronicallycycle the device on and off.

Figure 14 - IC H Bridge


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Figure 15 - IC H Bridge on solderless breadboard

The user selects either heating or cooling on the front panel; these buttons choose whether theheating or cooling logic statement is used for each device. By cycling the thermoelectric deviceon and off a fairly uniform hydrogel temperature is produced.


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Figure 16 - LabVIEW block diagram

Figure 17 - LabVIEW front panel


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The following graphs show heating and cooling data from the excel file that is written at the end

of each test. The yellow shaded areas show the desired temperature range. The horizontal red

line shows the temperature the logic was set to toggle at in LabVIEW. The blue line is the

thermoelectric

device, notice it

changes

temperature very

quickly. The green

line is the

temperature of the

hydrogel, notice it

reaches the desired

temperature more

slowly. Once the

hydrogel reachesthe desired

temperature the

thermoelectric is

turned off; when

the hydrogel returns

to a temperature

outside of the logic

temperature the

device

thermoelectric isturned back on.

This toggling logic

allows us to cycle

the device on and

off to maintain a

desired tray

temperature within

just a few degrees.

Figure 19 - Heating Test of Single Module

Figure 18 - Cooling Test of Single Module


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Analytical Thermal Model

This thermal model was created in order to:

1. Increase our understanding of thermoelectric device functionality2. Determine if a heatsink is necessary. If so, predict the minimum size requirements3. Evaluate how the device will perform over a range of input currents and select the most

appropriate application current.

The non-intuitive behavior of the thermoelectric devices led to an interesting analytical thermal

model. The following equations describe how heat flows into the cold side and out of the hot

side of the device . As demonstrated by the following equations, heat flow is a function of

applied current, Seebeck Coefficient, thermal conductivity and electrical resistivity (thus Joule

Heating) of the internal materials.

Where

Qh is the heat flow from the hot side of the thermoelectric, Qc is the heat flow into the cold

side of the thermoelectric, Th is the temperature of the hot side of the thermoelectric, Tc is the

temperature of the cold face of the thermoelectric and I in the input current.

Approximate material properties:

= +1

2

= 1

2

,

P P N N P P N N

P N P N

A A L LK RL L A A


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Number of couples, N: 17

Element width (in), W: 0.025

Element length (in), L: 0.040

We modeled the thermal path from the interior of the body, through the skin, through thedevice and passing into the surrounding air.

Figure 20 - Exploded View of Thermal Path and Corresponding Thermal Resistance Diagram

For steady state, the amount of heat flowing from the body through the device and into the

thermoelectric device had to be equal to Qc, the heat flow into the thermoelectric. And the

heat flow out of the thermoelectric Qh had to be equal to the heat flow through the heat sink

and into the air. Thus we were able to write a pair of simultaneous equations, one for each

face of the thermoelectric device.

h = + )

) =

(


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Note: Rresultant was the equivalent resistance of the skin and device up to the cold face of the

thermoelectric device.

After substituting in the material properties, we were left with two equations and four

unknowns; the area of the heat sink, the applied current, the temperature of the cold face ofthe thermoelectric and the temperature of the hot face of the thermoelectric. By substituting a

range of values for the independent variables, heat sink area and applied current, we were able

to solve for the temperatures of the thermoelectric faces. We then used this information to

calculate the speed of heat flow for the given configuration and used this to calculate the

maximum temperature experienced by the hydrogel.

In order to visualize the results, we wrote the following Matlab program:

% One dimensional conduction from skin to TEDT_body=308; % K body temperatureA=.000044; % m^2 cross sectional area, all faces are equal area

k1=.3; % w/mk thermal conductivity of human skin/fatL1=.003; % m thickness of human skin/fatR1=L1/(k1*A); % resistance through skin/fat

k2a=.15; % w/mk thermal conductivity of PDMSk2b=.56; % w/mk thermal conductivity of waterL2=.002; % m length of composite PDMS/Water layerR2a=L2/(k2a*.5*A);R2b=L2/(k2b*.5*A);R2=1.0/(1.0/R2a+(1.0/R2b)); % resistance through parallel water and PDMS

k3=.56; % w/mk thermal conductivity of waterL3=.003; % m length of hydrogel layerR3=L3/(k3*A); % resistance through hydrogel

k4=237; % w/mk thermal conductivity of AluminumL4=.5; % length of Aluminum layerR4=L4/(k4*A); % resistance through Aluminum

Req=R1+R2+R3+R4 ;% equivalent resistance from skin to TED

% Heat transfer to/from the TEDap_minus_an=.00043; % V/K Seebeck Coefficientlam_p=1.4; % W/mK thermal conductivitylam_n=1.4; % W/mK thermal conductivityrho_p=1*10^-5; % Ohm-meter electrical resistivityrho_n=1*10^-5; % Ohm-meter electrical resistivityN=17; % Number of elements

Ew=.000635; % m width of element (I think the element is square so this is the widthand length)Ap=Ew*Ew; % m^2 P element areaAn=Ew*Ew; % m^2 N element areaEl=.001016; % m length of element (I think this is actually the height)K=((lam_p*Ap)/El)+((lam_n*An)/El); % w/mK thermal conductivity of TEDR=((rho_p*El)/Ap)+((rho_n*El)/An); % Ohms

% Convection from the face of the TED to the airh=15; % w/m^2K convection coefficient for free convection over TED face


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T_sur=296; % K temperature of surrounding airA_heatsink=.000044; % m^2 initial value for area of heatsink

% defining variables for the hydrogelR_hydro=R1+R2; % resistance between body and hot side of hydrogelT_hydro_max=0; % initializing the max hydrogel temperature

% setting up the 2 simultaneous equations% h*A_heatsink*(Th-T_sur)=N*(ap_minus_an*I*Th-K(Th-Tc)+.5*(I^2)*R);% (T_body-Tc)/Req=N*(ap_minus_an*I*Tc-K(Th-Tc)-.5*(I^2)*R);% rearranging to find Cx=D

% I=input current in ampsI=0;

% Th=temp of TED hot sideTh=0; % initializing Th

% Tc=temp of TED cold sideTc=0; % initializing Tc

% establishing looping vectorloop=linspace(.01,2, 100); % 250);loop2=linspace(.0022,.004, 100); % 250);Heat_Sink_Array=[];QQ=[];mydata=[];l=0;for I=loop % increasing current

%Icount=Icount+1;Heat_Sink_Vector=[];Qloss = [];Theat_cold =[];l=l+1;k=0;

for A_heatsink=loop2 % increasing AreaC1=h*A_heatsink-N*ap_minus_an*I+N*K; % coefficient of Th in first equationC2=(1.0/Req)+N*ap_minus_an*I+N*K; % coefficient of Tc in second equationC=[C1,-N*K; -N*K, C2]; % coefficient matrixD=[((N/2.0)*I^2*R+h*A_heatsink*T_sur); ((N/2.0)*I^2*R+(T_body/Req))];X=C\D; % solving for Th and TcT_hydro_max=T_body-(T_body-X(2))*(R_hydro/Req);Q=(1/Req)*(T_body-X(2));mydata=[mydata; I, A_heatsink, X(1)-273, X(2)-273, T_hydro_max-273, Q];k=k+1;Temp(k,l)=[T_hydro_max-273];

end % end for heatsink loopfprintf('I value %f \n', I)

end% end for temp max loop

% Generate 3-D plot of current, surface area and Temp[x,y]=meshgrid(loop,loop2);surf(x,y,Temp);xlabel('Current (Amps)')ylabel('Surface Area (m^2)')zlabel('Temp (C)')AZ=130;EL=30;view(AZ,EL);


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Which produces the following graph:

Figure 21 - Maximum Hydrogel Temperature as a function of Heat Sink surface area and Input Current

As we would expect, as the surface area of the heatsink increases, heat is expelled more easilyand the maximum temperature of the hydrogel diminishes. Also as expected, low input current

results in insufficient cooling. But counter intuitively, increasing input current does not continueto improve cooling. We had expected a thermoelectric device cooling at full blast maximum

input current to produce maximum cooling, but instead we see that as the input current increases

past a certain range, Joule Heating begins to overpower the Peltier Effect and the maximumtemperature in the hydrogel begins to rise dramatically.

This analysis process was repeated for a module in contact with our PMMA testbed. When the

convection coefficient produced by a small electronics fan was assumed to be 12 W/m2K thismodel predicted hydrogel temperatures that were within 2 degrees of experimentally measured

values.

Conclusions from Analytical Thermal Model A heat sink will be necessary to adequately cool our device The heat sink should have a minimum surface area of at least .0022m2 For very low or very high input current Joule Heating over powers the Peltier Effect

and the steady state temperature of the hydrogel rises dramatically For coolest hydrogel, input current should be .8A-1.2A


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ANSYS IcePak Finite Element Analysis

Introduction

A model of our devicewas created in ANSYS IcePakto the geometric specificationsdetailed in our CAD model,but disregarding internal radii,ledges and small geometricfeatures that were unlikely tohave a significant impact onthe device temperature profile.A rendering of the deviceassembly is shown in Figure22 - Device, Test bed and HeatSink in ANSYS IcePak. Ourfirst step was to calibrate the model by first modeling the device in contact with the test bed andthen comparing the temperatures predicted by ANSYS IcePak to those measured experimentally.We then used the model to investigate how proximity of heating and cooling modules affectedhydrogel temperature and lastly to predict how the hydrogel temperature would be changedwhen, instead of the test bed, the device was in contact with skin.

Model Setup

In our IcePak Model we placed theassembly in a 0.1 m x 0.1 m x 0.1 m cabinetopen on all sides except for the bottomsurface, thus mimicking our device and testbed sitting on a table. Air was forced over theassemblys heat sinks from a position thatwas very close to where we had placed asmall electronics fan. The heat sinks weremodeled realistically but were simplifiedslightly. The thermoelectric devices used inthe actually model were created using a

macro native to the IcePak program inconjunction with data that we received fromthe manufacturer. The thermoelectric macrowas one of the primary reasons that we choseto analyze our device in IcePak instead ofanother Finite Element Analysis program dueto the ease of creating an accurate model of a

Figure 23 - IcePak Model Setup

Figure 22 - Device, Test bed and Heat Sink in ANSYS IcePak


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thermoelectric in this program. This macro allowed us to identify a number of characteristics ofthe thermoelectric including materialproperties, size and number ofcouples and applied current.

Results and Discussion

TEST 1

We began by mimicking ourtest bed set up, with the theroeoelctricexperiencing 1A input current, andadjusted the cubic flow rate of thefan within reasonable values until thesteady state cooling value of thehydrogel was sufficiently close toexperimentally measured values. Theresults of this model can be seen inFigure 27 - Three ModulesExperiencing Cooling. Since the

purpose of our Finite ElementAnalysis was to COMPARE howproximity between modulesinfluences temperature, we argue thatthis initial calibration to ensure thatthree modules experiencing coolingclosely matched experimental valueswas appropriate.

Figure 24 - Screen Shot of Thermoelectric Device Macro in ANSYS

IcePak

Figure 27 - Three Modules Experiencing Cooling

Figure 28 - Steady State Experimental Data compared to Calibrated

IcePak Predictions


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TEST 2

We then ran another test wherethe central module remained in acooling state and the modules adjacent

to it were heated. While we continuedto apply 1A to the cooling module, weapplied a reduced current to theheating module. Our control systemswitches on and off to hold this steadytemperature and this on/off results inan average input current which is lessthan the maximum current that would

be applied if held on continuously.

Again, the purpose of our FEM modelwas to evaluate the effects of heat bleeding, thus it was appropriate to place our cooling module

close to heated modules that would be producing the same amount of heat as heated modulesbeing controlled by our control system. As can be seen in Figure 25 - Cooled Module inProximity to Two Heated Modules, this configuration resulted in an increase in steady statecooling temperature of the hydrogel of 6 degrees Fahrenheit. This steady state cooling value canbe interpreted as the coolest possible temperature with a thermoelectric device runningcontinuously. A steady state cooling temperature of 63 F means that our control system couldcycle on and off and produce a cold temperature of 63 F or greater. Thus although there was asmall increase in the temperature of the hydrogel this value is still more than 44 F below theLCST of the hydrogel.

TEST 3The last model replaced thetest bed with a representation ofhuman skin. Human skin was againmodeled as it was in the AnalyticalThermal Model, as a constant internalbody temperature of 96F, with a3mm layer of fat with a thermalconductivity of .3 W/mK. This testwas performed to determine if thecooling provided by the

thermoelectric devices would besufficient to keep the hydrogeltemperature below the LCST. Theresults of this test can be seen inFigure 26 - Three Cooled Modules in Contact with Skin. The average temperature of thehydrogel was increased to 70F. Although contact with the body did significantly increase thetemperature of the hydrogel, this higher temperature was still more than 37 F below the LCST,the temperature at which the hydrogel experiences the phase change which results in rapid

Figure 25 - Cooled Module in Proximity to Two Heated Modules

Figure 26 - Three Cooled Modules in Contact with Skin


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medication release. This large margin proves that our chosen thermoelectric devices will be ableto sufficiently cool the hydrogel even when the device is in contact with skin.

Conclusions from the ANSYS IcePak Thermal Model 1 A applied current for cooling, adjusted cubic flow rate of small electronics fan and

reduced applied current to mimic control system heating accurate predict thebehavior of our device

Heat bleeding between modules does occur, but is very small and although itincreases the steady state cooling temperature of the hydrogel, this temperature isstill 44F below the LCST of the hydrogel

Contact with skin further increases the steady state cooling temperature of thehydrogel, but this increased temperature is still 37F below the LCST of thehydrogel.

Our device has significant margin between steady state cooling hydrogeltemperature and the LCST, thus we predict that even when near to heating modulesand in contact with skin, our thermoelectric devices will be powerful enough to

keep the hydrogel below release temperatures.


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Release Rate Testing

Motivations for Release Rate Testing

1) Confirm that our control system can properly heat the hydrogel to induce protein release2) Investigate how protein release rate changes as concentration in the hydrogel diminishes 3) Investigate how protein release rates can be manipulated by applying cycles of heating and

cooling

Experimental Procedure1) 80 L of this Composite Hydrogel Solution was pipetted into the aluminum tray and photo-

polymerized under UV light for 3 minutes2) 0.3 mL water injected into each cavity of the test bed3) Modules with hydrogel inserted through the top of the PDMS casing4) Artic Silver thermal epoxy and heat sink applied to the thermoelectric surface 5) After each test session, all water removed from testbed and stored and test bed was refilled

with fresh water6) BCA assay used to characterize protein release

a) Calculated absorbency of samples in spectrometer at 562 nm wavelengthTwo Modes of Diffusion1) The protein is released from the PNIPAM-AAm

a) Cause: The PNIPAM-AAm becomes hydrophobic above the LCST2) The protein makes its way through the hydrogel

a) Cause: Concentration gradientThus we would expect to see a delay between when the protein is released from the PNIPAM-AAm and when it actually exits the hydrogel

In many ways the culmination of this project was the medication release testing. Only bydemonstrating that our device could actually induce and control the release of medication fromthe hydrogel could we conclude that our device worked. From these tests we hoped todemonstrate a few key concepts. First, we simply wanted to demonstrate that by using our deviceto heat and cool the hydrogel we could influence the way medication was released. Second, wewanted to develop a relationship between the amount of medication in the device and themedication release rate. And finally, we wanted to demonstrate that we could produce a desiredrelease profile by manipulating the way we applied heating and cooling to the hydrogel. Toconduct these tests we fabricated a test bed capable of holding three modules at one time. Each

module was held over a chamber filled with water so that when it released, the medication wouldbe captured in the chamber. Each chamber was isolated from the other two chambers so that wecould measure the release from each module. To begin a test we would load each module with ahydrogel impregnated with Bovine Serum Albumin. For each sample, we would remove thewater in each chamber and replace it with fresh water, this would allow us to track the change inrelease rate as a function of time as well as other variables.


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24

TEST 1

For our first test we wanted to determine a baseline release for our hydrogel samples. In theorywe would love to see that the hydrogel did not release any medication until it was brought abovethe critical temperature. Unfortunately from the literature we knew that this was not the case and

we shouldexpect to seesome releasebelow thecriticaltemperature.The purposeof the first testwas toquantify thisuncontrollable

release. To dothis we loadeda module withBSA and let itsit at roomtemperaturefor 7 hours.The results ofthis test werethat we sawabout 12.8% of thetotal medication in thehydrogel released. The next step for us was to conduct this same test except with the hydrogelheld above the critical release temperature, remember this should cause the hydrogel to releasethe medication. For this test we held the device at approximately 107F. After conducting thisexperiment we saw that 38.8% of the total medication in the device had been released. Seeingthat the amount of medication released was significantly greater in the heating test than it was inthe room temperature test, we concluded that our device was causing the hydrogel to release.With a positive result from our first test we were able to move on to our next set of testing. SeeFigure 27 - Cumulative Protein Release for Heated and Room Temperature Control, for testresults.

TEST 2

For our next test we wanted to see what effect cycling the device above and below the criticaltemperature would have on medication release. To do this we loaded each module withmedication and then held the device at approximately 107F for 30 minutes followed by holdingthe device at approximately 68F for 90 minutes. We continued with 30 minutes of heating, 90minutes of cooling and finally 30 minutes of heating. Every 30 minutes we changed the water in

Figure 27 - Cumulative Protein Release for Heated and Room Temperature Control


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25

Figure 28 - Protein Release in Response to Uniform Heating/Cooling Cycle

the capture chambersso that we couldmeasure the release in30-minute intervals.What we found was

that our greatestamount of releaseoccurred during thefirst 30 minutes,which corresponded tothe first 30 minutes ofheating. During thenext 90 minutes ofcooling we continuedto measure release,however it decreased

over this time period.During the nextheating we again sawan increase in themedication release;however this release wasless than the amount wesaw in the first heating cycle. During the next 90 minutes of cooling we again saw release at adecreasing rate and during the final heating cycle we saw a very small increase in the amount ofmedication released. We were able to make two major conclusions from this test. First, we wereable to see that while the medication was released during the heating portion of the test asignificant amount of time was required for the medication to diffuse out of the device and intothe capture chambers. This delayed response is why we saw the decreasing amount of releasethroughout the cooling portions of the test. The second conclusion we were able to make wasthat overall rate of medication release is a function of the concentration of medication in thedevice. When the concentration is high in the beginning, 30 minutes of heating produces a largerelease, but when the concentration is low, near the end of the test, the 30 minutes of heating willproduce a much smaller release. See Figure 28 - Protein Release in Response to UniformHeating/Cooling Cycle, for release results.

TEST 3

For our third and final test we wanted to try to show that by adjusting the duration of the heatingcycle we could minimize the initial burst release and produce a fairly even amount of medicationrelease for each heating cycle. To accomplish this we decided to decrease the amount of initialrelease by making our first period of heating last for only 15 minutes. This heating was followedby 90 minutes of cooling. The second heating was applied for 30 minutes, twice as long as theinitial heating. This was followed by 90 minutes of cooling. Finally we applied heat for 45minutes, three times as long as the initial heating. What we saw from this test was a much more


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26

uniform releaseprofile. Bybeginning withheating for a shortperiod of time and

increasing it foreach subsequentperiod of heating wewere able to balancethe releasethroughout the testmuch moreeffectively. Fromthis we concludedthat we couldmanipulate the

release profile bychanging the waywe applied theheating and coolingcycles. See Figure29Protein Release inResponse to Non-Uniform Heating/Cooling Cycle, for release results.

Conclusions from Release Rate Testing Heating the hydrogel indeed resulted in increased BSA release when compared to

room temperature control Two types of diffusion are present. Release of BSA from the PNIPAM-AAm

caused by phase change at LCST and also release of BSA from device which is alsoa function of the protein concentration within the device. This results in initialburst release and a delay between the cessation of heating and the significantdiminishment of release.

Temperature cycling will impact medication release profile Release rate diminishes as total concentration of protein within the device

decreases. Thus shorter heating cycles at the beginning of medication release andlonger heating cycles when the concentration had been diminished can result inmore uniform release doses.

Figure 29 - Protein Release in Response to Non-Uniform Heating/Cooling Cycle


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27

Project Conclusions and

Recommendations for Future Projects

Project Conclusions

Material design consideration led to thermally responsive hydrogel capable of medicineimpregnation, stainless steel tray that was thermally conductive and capable of beingsterilized. The epoxy was chosen for thermal conductivity and biocompatibility. PMMAwas chosen for the alignment structure for its machinability and stiffness. Thermocouplestake advantage of the voltage induced when the two materials connected experience atemperature shift. Thermoelectric devices rely on materials that exhibit the Peltier Effectand PDMS was chosen for the casing due to its strength, flexibility, manufactuability andbiocompatibility.

Analytical thermal modeling gave insight into the functionality of thermoelectric deviceswhile guiding input parameters like the area of the needed heat sink and the appropriateapplied current.

Finite Element Analysis showed that heat bleeding between modules was negligible andpredicted that even when in contact with skin, the thermoelectric devices would becapable of keeping the hydrogel cooled to below the LCST.

Prototype fabrication demonstrated that modules could be controlled individually Release rate testing showed that our device could heat the hydrogel enough to induce

medication release. It also demonstrated two types of diffusion. Release of BSA from thePNIPAM-AAm caused by phase change at LCST and also release of BSA from devicecaused by internal concentration gradient. This results in initial burst release, which can

be counteracted by applying shorter initial heating cycles and longer subsequent heatingcycles.

Analysis, modeling, fabrication and testing has demonstrated proof of concept.Recommendations for Future Projects

Further release rate characterization to ensure consistent repeatability and improvedcontrol

Thermal Managemento Liquid Cooling/ Phase Change Heat Sinks to replace current temporary design

Removal of Exudateso Piezoelectric Micropumps, Microchannels, etc to remove bodily fluids released

from wound Device Portability

o Battery powered/ FPGA, wires incorporated into PDMS casing Custom User Interface for bandage programming Additional Drugs Designed for Topical Application Exploration of non-topical device applications, possibility of implanting within body


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Appendix A:

Fabrication ProcessesoHydrogeloAluminum TrayoPMMA InsertoPDMS HousingoTest Bed


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F.1 - Hydrogel

Drug Loading

1.

Dissolve 200 mg of PNIPAM-AAm in M mL of di-ionized water (4% weightby volume) Note: the shiny pieces will not fully disolve, so remove thesepieces. See Figure 30and Figure 31.

2. Add 50 mg of Bovine Serum Albumin to the solution (1% weight by volume)See Figure 32.

3. Stir for 3 days using a magnetic stirring plate4. Dialize the loaded nanoparticles in 10,000 MWCO (Molecular Weight Cut Off)

tubing in 50 mL of di-ionized water. See Figure 37.5. Carry out dialisis at 4C for 3 hours6. Collect 3 mL of the dialized water and measure to confirm expected

PNIPAM-AAm concentration

Composite Hydrogel Fabrication1. Put 800 L of the drug loaded nanoparticles in a separate dish2. Add .15g of PEG-DA and mix using the magnetic stirring plate until fully

dissolved. See Figure 33.3. In a separate dish, combine 100 L ethanol with 100 L di-ionized water4. Add .015g of Irgacure to the ethanol/water solution. See Figure 39.

Note: Irgacure is the photoinitiator so must be protected from lightexposure. Mix water, ethanol and irgacure in a tube that has beenwrapped in aluminum foil. Mix using a Speed Control Mixer.

5. Combine Irgacure and drug loaded solutions. Mix using magnetic stirring plate.6. Pipette about 68 L of the solution into the metal device tray.7. Expose to UV light for about 3 minutes

Note: As heating will make the PNIPAM-AAm release the drugs, be sure toplace the device on an ice pack while exposing it to UV light.

Figure 30 - PNIPA-AAM

Figure 31 - Shiny non-

dissolvable PNIPA-AAM film

Figure 347 - 10,000 MWCO Tubing Figure 39 - Irgacure Photo

initiator

Figure 33 - PEG-DA

Figure 32 - Bovine Serum

Albumin


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Step-inTop Hat

F.2 - Tray

Tray Overview

The portion of the design referred to as the tray is responsible for

the containment of the hydro-gel and acts as the interface between thehydro-gel and the heat source. The tray will be made from surgical gradestainless steel and will be machined from a solid piece of stock with a CNCor manual end mill. The basic dimensions for the tray are 8.6mm x 8.6mmx 3.5mm (length, width, height respectively). Refer to Figure 40 - Pro-Emodel of finished tray.

Stock Preparation

1. Begin by selecting a piece of stock which has length and width dimensionsslightly larger than 8.6mm x 8.6mm.

2. Cut the height of your stock to approximately 152mm.3. The next step is to machine the length and width dimensions to the correct

size. Select a end mill and make passes at 1200 rpm with a linear feedrate of 0.100 in/sec and a depth of no greater than 0.020in. repeat thisprocedure as many times as is necessary to achieve length and widthdimensions of 8.6mm x 8.6mm.

4. Finally use a ban saw and cut the stock into slugs with a height of 6mm.The final slug should measure 8.6mm x 8.6mm x 6mm.

Outside Surface

1. The first step is to square off the top and bottom of the slug.2. Orient the slug in the vise so that the 8.6mm length and width

dimensions are in the x and y-axis. Use a end mill at 1200rpm for the following procedures.

3. Since the top hat section of the tray is notsquare the machining process can be brokeninto two sections. Each section will consistof one set of parallel sides.

4. Begin with the first set of parallel sides andmake passes so that the height of the TopHat section is 3.0mm and the Step-inmeasures 0.9mm. Refer to Figure 41.

5. Next move to the other set of parallel sides and againmachine the height of the Top Hat section to 3.0mm,thistime the Step-in should measure 1.3mm.

Figure 35 - ProEngineer Model of

Finished Tray

Figure 36 - Dimension of First Parallel Sides


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Inside Surface

1. At this point the outer surface should be machined to size with theexception of the bottom surface.

2. Remove the tray from the vise and flip it over so that the top hatportion of the tray is on the bottom, reinsert the tray into the vice sothat the sides measuring 6.8mm are in the x-axis.

3. The next step is to machine the bottom surface (now the top surface)to its final thickness of 0.5mm.

4. Use a end mill at 1200 rpm with a linear feed rate of 0.100in/sec. Make passes with a depth of 0.020in until the thickness ofthe tray lip is about 0.040in. Reduce the depth of cut to 0.010inand make passes until the bottom surface of the tray has been machined to

a thickness of 0.5mm (0.020in).5. The next step is to hollow the inside of the tray. The inside dimensions ofthe tray will measure 5.8mm (x-axis) x 5mm (y-axis). Start with an 11/64end mill at 1500 rpm and begin removing material in 0.020in increments.Continue to remove material until the depth of cut is 0.118in (3mm).

6. Replace the 11/64 end mill with a 3/64. Use this end mill to remove thematerial that the 11/64 end mill could not remove.

7. Run the 3/64 end mill at 1700 rpm with a linear feed rate of 0.100 in/secand make passes with a depth of cut of 0.010in. Repeat this process until adepth of 0.118in (3mm) is reached. Refer to Figure 42.

Figure 37 - ProEngineer Model of Finis

Tray Bottom View

Figure 38 - Image of Inverted Tray Loaded with Hydrogel


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F.3 - PMMA

Step 1First, use a band saw to cut a long column of PMMA into aroughly 10mmx10mmx7mm rectangular prism.

Step 2Use a inch diameter end mill to machinethe rectangular prism down to the final desired external dimensions of8.6mmx8.6mmx5.5mm. The machining is done at1300 RPM with a feed rate of 10mm/min for this and

all other end mill operations.

Step 3Use a 13/64 inch diameter end mill to drill a hole 3.34mm deepinto the center of one of the 8.6mmx8.6mm faces of the block.

Step 4Use a 3/64 inch diameter end mill to enlarge the hole intoa 6.8mmx6mm rectangular cavity with rounded corners of 3.34mmdepth. Perform the operation first at a 1.67mm depth and thenagain at the 3.34mm depth. The reason for doing it this way is to

prevent the small end mill from being damaged during themachining process.

Step 5Use a 13/64 inch diameter end mill to cut a hole 2.16mm intothe center of the face opposite that which was previously being workedon. The mill should then be used to machine through a wall parallel toa 6mm side of the previously milled cavity, staying at a 2.16mm depth.

Step 6Use a 13/64 inch diameter end mill to enlarge this hole to arectangular cavity with rounded corners which is 8mmx6.6mm at adepth of 2.16mm. The 8mm dimension is measured from the partof the wall which has been removed. Like Step 4, this should bedone once at a1.08mm depth and then again at the desired 2.16mmdepth.

Figure 39: Image after Step 1







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F.4 - Polydimethylsiloxane (PDMS)

1. Measure out the appropriate volume necessary to generate the PDMSblanket.

2. Mix the PDMS base agent and the curing agent in a 10:1 weight ratio.See Figure 50.

3. Thoroughly stir the solution for about 10 minutes until a thick, uniformtexture is reached.

4. Coat the mold in PTFE (polytetrafluoroethylene) spray to lubricate foreasy removal of PDMS after it has been cured.

5. Pour the mixed PDMS solution over the mold making sure that there isenough material within each well of the mold. See Figure 51.

6. Place the PDMS mold into a vacuum chamber for about 20 minutes untilall of the gas bubbles have been raised to the surface of the solution. See

Figure 52.

7. After degassing the solution, place the mold into an oven atapproximately 80C for 2 hours to allow the PDMS to cure. See Figure 53.8. Remove from oven and let stand until room temperature has been

reached.

9. Take care to remove the PDMS from the mold; the PDMS material isflexible but prone to tearing. See Figure 54.

Figure 45 - Weigh Mixture

Components

Figure 54

Completed PDMSCasing

Figure 46 Aluminum Mold

Figure 52

Degas Solution inVacuum Chamber

Figure 47

Place Mold into Oven


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F.5 Test Bed

Test Bed Overview

The test bed is a key component because it is where we conduct all of our release tests.The design criteria for this piece of equipment were as follows: Allow us to test a system of threedevices arranged side by side, allow for maximum visibility of the collection reservoir during thetesting procedure and consist of three collection reservoirs of equal volume.

Fabrication1. We began with a block of Plexiglas and

cut it to approximately 2.5 by 1.25 by

0.75.2. Next we brought it to an end mill and

machined out cavities to serve ascollection reservoirs. Cavities measuredapproximately 0.8mm by 0.8mm by 10mmdeep.

3. Finally for test bed 2 we glued a magneticstrip to the top surface.

4. For test bed 3 we glued the PDMS blanketdirectly to the top surface.

5. Final assembly of test bed 3 is shown inFigure 48Test Bed 3 Final Assembly.

Figure 48 Test Bed 3 Final Assembly


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Appendix B:

Bibliography


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Bibliography

American Burn Association. Burn INcidence Fact Sheet. 2005 1-1. 2010 28-11

.

Mayo Clinic. Burns: First Aid. 2010 5-11. 2010

28-11 .

Sabnis, Wadajkar, Aswath & Nguyen Factorial Analyses of Photopolymerizable

Thermoresponsive Hydrogels for Protein Delivery

Sally Abston MD, Patricia Blakeney PhD, Manubhai Desai MD, Patricia Edgar RN, CIC,John P

Heggers PhD, David N Herndon MD, Marsha Hildreth RD, Ray J Nichols Jr. MD. Resident

Orientation Manual. 2010 1-6. 2010 28-11 .

United States Department of Labor. Burn Accidents. 1994 6-5. 2010

.

Web M.D. Skin Grafts, Split Thickness. 2010 11-5. 2010 2-12

.


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Appendix C:

Dimensioned Drawings


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Appendix D:

Material Data Sheets


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Arctic Silver Incorporated MSDS # AS5_3

Page 1 of 2

SECTION 1: CHEMICAL PRODUCT AND COMPANY INFORMATION

Company Address:

9826 W. Legacy Ave.

Visalia, CA 93291

Product Information: 559-740-0912

Medical Emergency Toll Free: 877-740-5015 Prepared by: Nevin House

Medical Emergency Alternate: 303-739-1110 Revision Date: January 25, 2011

Product Identification

Arctic Silver 5 High-Density Polysynthetic Silver Thermal CompoundProduct Code: AS5SECTION 2: COMPOSITION/INFORMATION ON INGREDIENTS

Product Ingredient Information CAS No.Silver (Metallic) 7440-22-4

Boron Nitride 10043-11-5

Zinc Oxide 1314-13-2

Aluminum Oxide 1344-28-1

Ester Oil Blend Non-hazardous

SECTION 3: HAZARD IDENTIFICATION

Emergency Overview: Grey grease. This product is nonflammable. Liquid will irritate eyes.

Potential Health Effects:

Eyes: This product is an eye and mucus membrane irritant.

Skin: Not expected to be a skin irritant. Repeated and prolonged skin contact could cause minor skin irritation.

Ingestion: Silver ingestion may result in generalized argyria.Inhalation: No specific information available.

Pre-Existing Medical Conditions Aggravated by Exposure: eye

SECTION 4: FIRST AID MEASURES

Eyes: Immediately flush with large amounts of water. After initial flushing, remove any contact lenses and continue flushing for at least 15 minutes. Have eye

examined by a Physician.

Skin: Remove contaminated clothing and wash skin with soap and water. Get medical attention if irritation develops/persists. Wash clothes separately before reuse.

Ingestion: If appreciable quantities are swallowed, seek medical advice.

Inhalation: Not likely route of exposure. If inhaled and irritation occurs, remove to fresh air. If irritation persists, call a Physician.

SECTION 5: FIRE FIGHTING MEASURES

Flash Point: > 600F (Setaflash) LEL/UEL: NA (% by volume in air)

Extinguishing Media: Use carbon dioxide or dry chemicals for small fires, aqueous foam or water for large fires involving this material.

Fire Fighting Instructions: Remove all ignition sources. Closed containers may rupture due to build-up of pressure when exposed to extreme heat. Fight fire from a

safe distance. As in any fire, wear self-contained breathing apparatus (pressure demand, OSHA/NIOSH approved or equivalent) and full protective gear.

SECTION 6: ACCIDENTAL RELEASE MEASURES

Large Spills: Remove all sources of ignition (sparks, open flames, etc.). Wear self-contained breathing apparatus and appropriate personal protective equipment

Ventilate area and contain spill with sand or other absorbent material. Collect spill by scooping up liquids and absorbent material and place in a sealed metal containe

for proper disposal. Do not flush to sewer. Prevent material from entering storm sewers, ditches that lead to waterways and ground.

Small Spills: Absorb spill with absorbent material, then place in a sealed metal container for proper disposal.

SECTION 7: HANDLING AND STORAGE

Overheating may cause container to rupture. Use explosion proof electrical equipment. Containers must be kept closed and ventilation provided to prevent vapo

concentration build-up. Store in a cool dry place. Do not breathe vapor or get liquid in eyes, or on skin and clothing. Keep away from heat or sources of ignition

Check all containers for leaks. Wear protective clothing as in section above. Avoid prolonged breathing of vapors or contact with skin. Ensure that all equipment i

grounded to prevent static discharge. Containers of this material may be hazardous when emptied due to solid or vapor residue. All hazard precautions given in thi

data sheet must be observed for empty containers.

KEEP OUT OF REACH OF CHILDREN.

SECTION 8: EXPOSURE CONTROLS/PERSONAL PROTECTIONExposure Guidelines:

CHEMICAL NAME ACGIH TLV OSHA PEL ACGIH STEL

Silver 0.1 mg/m3 0.01mg/m3 NA

Boron Nitride 10 mg/m3 10 mg/m3 NA

Zinc Oxide 10 mg/m3 (dust) 15 mg/m3 (dust) 10 mg/m3

Aluminum Oxide 10 mg/m3 (dust) 10 mg/m3 (dust) NA

Polyol Ester NA NA NA

NFPA and HMIS Codes: NFPA HMIS

Health 1 1

Flammability 1 1

Reactivity 0 0

Personal Protection - B

SECTION 9: PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Grey Grease Solubility in Water:


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1

1 0

He a l t h

Fi re

R e a c t i v i t y

P e r s o n a lP r o t e c t i o n

Material Safety Data SheetAluminum MSDS

Section 1: Chemical Product and Company Identification

Product Name: Aluminum

Catalog Codes: SLA4735, SLA2389, SLA3895, SLA1549,

SLA3055, SLA4558, SLA2212, SLA3715

CAS#: 7429-90-5

RTECS: BD0330000

TSCA: TSCA 8(b) inventory: Aluminum

CI#: Not applicable.

Synonym: Aluminum metal pellets; Aluminum metalsheet; Aluminum metal shot; Aluminum metal wire

Chemical Name: Aluminum

Chemical Formula: Al

Contact Information:

Sciencelab.com, Inc.

14025 Smith Rd.Houston, Texas 77396

US Sales: 1-800-901-7247International Sales: 1-281-441-4400

Order Online: ScienceLab.com

CHEMTREC (24HR Emergency Telephone), call:

1-800-424-9300

International CHEMTREC, call: 1-703-527-3887

For non-emergency assistance, call: 1-281-441-4400

Section 2: Composition and Information on Ingredients

Composition:

Name CAS # % by Weight

Aluminum 7429-90-5 100

Toxicological Data on Ingredients: Aluminum LD50: Not available. LC50: Not available.

Section 3: Hazards Identification

Potential Acute Health Effects:

Slightly hazardous in case of skin contact (irritant). Non-irritating to the eyes. Non-hazardous in case of ingestion.

Potential Chronic Health Effects:

CARCINOGENIC EFFECTS: Not available. MUTAGENIC EFFECTS: Not available. TERATOGENIC EFFECTS: Notavailable. DEVELOPMENTAL TOXICITY: Not available. The substance is toxic to lungs. Repeated or prolonged exposure

to the substance can produce target organs damage. Repeated exposure to a highly toxic material may produce generaldeterioration of health by an accumulation in one or many human organs.

Section 4: First Aid Measures

Eye Contact:
http://www.sciencelab.com/http://www.sciencelab.com/


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Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15

minutes. Get medical attention if irritation occurs.

Skin Contact: Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develop

Serious Skin Contact: Not available.

Inhalation:If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medicalattention immediately.

Serious Inhalation: Not available.Ingestion:

Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconsciousperson. If large quantities of this material are swallowed, call a physician immediately. Loosen tight clothing such as a collar,

tie, belt or waistband.

Serious Ingestion: Not available.

Section 5: Fire and Explosion Data

Flammability of the Product: Non-flammable.

Auto-Ignition Temperature: Not available.

Flash Points: Not available.

Flammable Limits: Not available.

Products of Combustion: Some metallic oxides.

Fire Hazards in Presence of Various Substances: Not available.

Explosion Hazards in Presence of Various Substances:

Risks of explosion of the product in presence of mechanical impact: Not available. Risks of explosion of the product inpresence of static discharge: Not available.

Fire Fighting Media and Instructions:SMALL FIRE: Use DRY chemical powder. LARGE FIRE: Use water spray, fog or foam. Do not use water jet.

Special Remarks on Fire Hazards: Not available.

Special Remarks on Explosion Hazards: Not available.

Section 6: Accidental Release Measures

Small Spill:Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on

the contaminated surface and dispose of according to local and regional authority requirements.

Large Spill:Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on thecontaminated surface and allow to evacuate through the sanitary system.

Section 7: Handling and Storage

Precautions:Do not ingest. Wear suitable protective clothing. If ingested, seek medical advice immediately and show the container or the

label. Keep away from incompatibles such as oxidizing agents, acids, alkalis.

Storage: Keep container tightly closed. Keep container in a cool, well-ventilated area. Moisture sensitive.


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Section 8: Exposure Controls/Personal Protection

Engineering Controls:

Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommendedexposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants

below the exposure limit.

Personal Protection: Safety glasses. Lab coat. Gloves.

Personal Protection in Case of a Large Spill: Safety glasses. Lab coat. Gloves.

Exposure Limits:

TWA: 5 (mg(Al)/m) from ACGIH (TLV) [United States] Inhalation (pyro powders, welding fumes) TWA: 10 (mg(Al)/m) fromACGIH (TLV) [United States] Inhalation (metal dust) Consult local authorities for acceptable exposure limits.

Section 9: Physical and Chemical Properties

Physical state and appearance: Solid.

Odor: Odorless.

Taste: Not available.

Molecular Weight: 26.98 g/mole

Color: Silver-white

pH (1% soln/water): Not applicable.

Boiling Point: 2327C (4220.6F)

Melting Point: 660C (1220F)

Critical Temperature: Not available.

Specific Gravity: Density: 2.7 (Water = 1)

Vapor Pressure: Not applicable.

Vapor Density: Not available.

Volatility: Not available.

Odor Threshold: Not available.

Water/Oil Dist. Coeff.: Not available.

Ionicity (in Water): Not available.

Dispersion Properties: Not available.

Solubility:

Insoluble in cold water, hot water. Soluble in alkalies, Sulfuric acid, Hydrochloric acid. Insoluble in concentrated Nitric Acid, hAcetic acid.

Section 10: Stability and Reactivity Data

Stability: The product is stable.

Instability Temperature: Not available.

Conditions of Instability: Incompatible materials, exposure to moist air or water.

Incompatibility with various substances: Reactive with oxidizing agents, acids, alkalis.

Corrosivity: Not available.


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Special Remarks on Reactivity:

Moisture sensitive. Aluminum reacts vigorously with Sodium Hydroxide. Aluminum is also incompatible with strong oxdizers,acids, chromic anhydride, iodine, carbon disulfide, methyl chloride, and halogenated hydrocarbons, acid chlorides, ammoniunitrate, ammonium persulfate, antimony, arsenic oxides, barium bromate, barium chlorate, barium iodate, metal salts

Special Remarks on Corrosivity:In moist air, oxide film forms which protects metal from corrosion. Aluminum is strongly electropositive so that it corrodes

rapidly in contact with other metals.

Polymerization: Will not occur.

Section 11: Toxicological Information

Routes of Entry: Not available.

Toxicity to Animals: Not available

Chronic Effects on Humans: Not available.

Other Toxic Effects on Humans:Slightly hazardous in case of skin contact (irritant). Non-hazardous in case of ingestion. Non-hazardous in case of inhalation

Special Remarks on Toxicity to Animals: Not available.

Special Remarks on Chronic Effects on Humans: Not available.

Special Remarks on other Toxic Effects on Humans:Acute Potential Health Effects: Skin: Exposure to aluminum may cause skin irritation. Eyes: Not expected to be a hazard

unless aluminum dust particles are present. Exposure to aluminum dust may cause eye irritation by mechanical action.Aluminum particles deposited in the eye are generally innocous. Inhalation: Not expected to be an inhalation hazard unless

it is heatedor if aluminum dust is present It heated or in dust form, it may cause respiratory tract irritation. Heating Aluminumcan release Aluminum Oxide fumes and cause fume metal fever when inhaled. This is a flu-like illness with symptomsof metallic taste, fever, chills, aches, chest tightness, and cough. Ingestion: Acute aluminum toxicity is unlikely. Chronic

Potential Health Effects: Skin: Contact dermatitis occurs rarely after aluminum exposure. Most cases of aluminum toxicityin humans are in one of two categories: patients with chronic renal failure, or people exposed to aluminum fumes or dust in

the workplace. The main source of aluminum in people with chronic renal failure was in the high aluminum content of thewater for the dialysate used for dialysis in the 1970's. Even though this problem was recognized and corrected, aluminum

toxicity continues to occur in some individuals with renal who chronically ingest aluminum-containing phosphate bindersor antacids. Inhalation: Chronic exposure to aluminum dust may cause dyspnea, cough, asthma, chronic obstructive lungdisease, pulmonary fibrosis, pneumothorax, pneumoconiosis, encephalopathy, weakness, incoordination and epileptiform

seizures and other neurological symptoms similar to that described for chronic ingestion. Hepatic necrosis is also a reportedeffect of exposure to airborne particulates carrying aluminum. Ingestion: Chronic ingestion of aluminum may cause Aluminum

Related Bone Disease or aluminum-induced Osteomalacia with fracturing Osteodystrophy, microcytic anemia, weakness,fatigue, visual and auditory hallucinations, memory loss, speech and language impairment (dysarthria, stuttering, stammerin

anomia, hypofluency, aphasia and eventually, mutism), epileptic seizures(focal or grand mal), motor disturbance(tremors,myoclonic jerks, ataxia, convulsions, asterixis, motor apraxia, muscle fatigue), and dementia (personality changes, altered

mood, depression, diminished alertness, lethargy, 'clouding of the sensorium', intellectual deterioration, obtundation, coma),and altered EEG.

Section 12: Ecological Information

Ecotoxicity: Not available.

BOD5 and COD: Not available.

Products of Biodegradation:

Possibly hazardous short term degradation products are not l ikely. However, long term degradation products may arise.

Toxicity of the Products of Biodegradation: The products of degradation are less toxic than the product itself.

Special Remarks on the Products of Biodegradation: Not available.


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Section 13: Disposal Considerations

Waste Disposal:

Waste must be disposed of in accordance with federal, state and local environmental control regulations.

Section 14: Transport Information

DOT Classification: Not a DOT controlled material (United States).Identification: Not applicable.

Special Provisions for Transport: Not applicable.

Section 15: Other Regulatory Information

Federal and State Regulations:

California prop. 65: This product contains the following ingredients for which the State of California has found to cause birthdefects which would require a warning under the statute: No products were found. California prop. 65: This product containsthe following ingredients for which the State of California has found to cause cancer which would require a warning under

the statute: No products were found. Connecticut hazardous material survey.: Aluminum Illinois toxic substances disclosureto employee act: Aluminum Rhode Island RTK hazardous substances: Aluminum Pennsylvania RTK: Aluminum Minnesota:

Aluminum Massachusetts RTK: Aluminum New Jersey: Aluminum New Jersey spill list: Aluminum California Director's Listof Hazardous Substances: Aluminum TSCA 8(b) inventory: Aluminum SARA 313 toxic chemical notification and release

reporting: Aluminum

Other Regulations:

OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200). EINECS: This product is on theEuropean Inventory of Existing Commercial Chemical Substances.

Other Classifications:

WHMIS (Canada): Not controlled under WHMIS (Canada).

DSCL (EEC):

HMIS (U.S.A.):

Health Hazard: 1

Fire Hazard: 0

Reactivity: 0

Personal Protection: B

National Fire Protection Association (U.S.A.):

Health: 1

Flammability: 1

Reactivity: 0

Specific hazard:

Protective Equipment:Gloves. Lab coat. Not applicable. Safety glasses.

Section 16: Other Information

References:


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-Hawley, G.G.. The Condensed Chemical Dictionary, 11e ed., New York N.Y., Van Nostrand Reinold, 1987. -Material safety

data sheet emitted by: la Commission de la Sant et de la Scurit du Travail du Qubec. -SAX, N.I. Dangerous Propertiesof Indutrial Materials. Toronto, Van Nostrand Reinold, 6e ed. 1984. -The Sigma-Aldrich Library of Chemical Safety Data,Edition II. -Guide de la loi et du rglement sur le transport des marchandises dangeureuses au canada. Centre de conformit

internatinal Lte. 1986. 037 Waste manifest or notification not required.

Other Special Considerations: Not available.

Created: 10/09/2005 03:39 PM

Last Updated: 11/06/2008 12:00 PM

The information above is believed to be accurate and represents the best information currently available to us. However, make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assum

no liability resulting from its use. Users should make their own investigations to determine the suitability of the information their particular purposes. In no event shall ScienceLab.com be liable for any claims, losses, or damages of any third party or

lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if ScienceLab.cohas been advised of the possibility of such damages.


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9025 Technology Dr. Fishers, IN 46038-2886800-387-0672 317-570-7020 Fax 317-570-7034

email:[email protected] www.bangslabs.comB E A D SB E A D SB E A D SB E A D SB E A D S A B O V E T H E R E S T

Material Safety Data Sheet

SECTION I - Chemical Product and Company Identification

Date Prepared March 11, 2002

Identity PolymethylMethacrylate (PMMA)

Company Information Bangs Laboratories, Inc. phone:317-570-70209025 Technology Drive fax:317-570-7034Fishers, Indiana 46038

SECTION II - Composition, Information on Ingredients

PolymethylMethacrylate suspended in water or as a dry powder.

SECTION III - Physical/Chemical Characteristics

Boiling Point 100C / 212F Glass Transition Temp 105C

Density 1.19g/cc Solubility in Water Emulsion

Appearance and Odor Brown liquid emulsion.

SECTION IV - Fire and Explosion Hazard Data

Extinguishing Media

Water Fog

Special Firefighting ProceduresN/A

Unusual fire and Explosion HazardsThe dried resin is flammable similar to wood. Burning dry resin emits dense, black smoke.

Suspended material is not flammable.


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SECTION V - Reactivity Data

IncompatibilitiesMay irreversably aggregate if frozen at 0C / 32F. Dried resin is combustible. Addition of

chemicals may cause coagulation.

Hazardous Combustion or Decomposition ProductsHazardous decomposition products: methyl methacrylate and carbon monoxide depending on

condition of heating and burning.

SECTION VI - Health Hazard Data

Hazards IdentificationEyes: Mild irritationSkin Contact: Short exposure; no irritation. Repeated prolonged exposure, especially if confined;

mild irritation, possibly a mild superficial burn.

Skin Absorption: Not likely to be absorbed in toxic amounts. Possibly weak sensitizer.Ingestion: Low single dose toxicity.Inhalation: No guide established. Considered to be low in hazard from inhalation.Systemic and Other Effects: None known.

First Aid MeasuresEyes: Flushing the eye immediately with water for 15 minutes is a good safety practice.

Physician should stain for evidence of corneal injury.Skin: Contact may cause slight irritation. Wash off in flowing water or shower. Wash clothing

before reuse. Treat as any contact dermatitis. If burn is present, treat as any thermal burn.

Ingestion: Low in toxicity. Induce vomiting if large amounts are ingested.

Inhalation: Remove to fresh air if effects occur. Consult medical personnel.Systemic: Human effects not established. No specific antidote. Treatment based on soundjudgement of physician and the individual reactions of the patient.

SECTION VII - Precautions for Safe Handling and Use

Handling and StorageVentiliation: Good room ventilation usually adequate for most operations.Respiratory protection: None normally needed. In cases where there is a likelihood of inhalation

exposure to dried particles, wear a NIOSH approved dust respirator.

Storage: Store at temperatures between 4C and 8C. Material may develop bacteria odor on longterm storage. No safety problems known. Do not freeze.

Accidental Release MeasuresAction to take for spills: Flush area with water immediately. Avoid unnecessary exposure andcontact.


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SECTION VII - Continued

Disposal ConsiderationsWill color streams and rivers to a milky white. Has practically no biological oxygen demand but willsettle out and form sludge or film. May plug up sanitary sewers. Divert to pond or burn solid waste

iin an adequate incinerator. Flush sewers with large amounts of water.

SECTION VIII - Control Measures

Respiratory ProtectionNone normally needed. In cases where there is a likelihood of inhalation exposure to dried

particles, wear a NIOSH approved dust respirator.

Wash/Hygenic Practices

Wash with soap and water when leaving work area and before eating, smoking and using restroomfacilities.

The information herein is given in good faith, but no warranty, expressed or implied, is made.

Refer questions or comments to Bangs Laboratories, Inc. (317) 570-7020.


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Material Safety Data SheetPEGDA

Section 1 Chemical Product and Company Identification

MSDS Name: PEGDA

Catalog Numbers: N/A

Synonyms: PEGDACompany Identification:

Glycosan BioSystemsPO Box 2321Park City, UT 84060

For information, call: 801-518-6971

Section 2 Composition, Information on Ingredients

CAS# Chemical Name Percent EINECS/ELINCS

26570-48-9 Poly(ethylene Glycol) Diacrylate,PEGDA

Varies unlisted

Hazard Symbols: None listed.

Risk Phrases: None listed.

Section 3 Hazards Identification

EMERGENCY OVERVIEW

Appearance: White to Yellow Powder. The toxicological properties of this material have

not been fully investigated. Caution! Avoid contact and inhalation.Target Organs: Risk of serious damage to eyes. Known irritant

For additional information on toxicity, please refer to Section 11.

Section 4 First Aid Measures

Eyes: Check for contact lenses and remove if present. Flush thoroughly with water whileopening eyelids for at least 15 minutes. If symptoms such as redness and irritation persist,

obtain medical attention.

Skin: Wash material from skin with soap and water and rinse thoroughly with clean water.

Obtain medical attention as needed or if irritation develops. Clean contaminated clothingbefore reuse.

Ingestion: May be harmful if swallowed. Only rinse month with water if person is

conscious. Obtain Medical attention as needed.

Inhalation: Remove person from source to fresh air; if not breathing give artificial

respiration. If breathing is difficult, give Oxygen.

Notes to Physician: Treat symptomatically and supportively.


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Section 5 Fire Fighting Measures

General Information: As in any fire, wear a self-contained breathing apparatus inpressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.

Extinguishing Media: Use agent most appropriate to extinguish fire. Suitable: Water

spray. Carbon dioxide, dry chemical powder, or appropriate foam.Flash Point: N/A

Autoignition Temperature: N/A

Flammability: Non-flammable

Unusual Fire and Explosion Hazards: As with any organic material, this product mayproduce toxic carbon monoxide and dioxide fumes if heated to decomposition and airborne

dust may present an explosion hazard.

Section 6 Accidental Release Measures

General Information: Exercise appropriate precautions to minimize direct contact with

skin or eyes and prevent inhalation of dust. Such as: respirator, chemical safety goggles,rubber boots, and heavy rubber gloves.

Spills/Leaks: Wear protective clothing and gloves. Absorb on sand or vermiculite andplace in closed container for disposal. Ventilate and wash spill area after material pick-up

is complete. Wash contaminated clothing before reuse.

Section 7 Handling and Storage

Handling: User Exposure: Avoid inhalation. Avoid prolonged or repeated exposure.

Storage: Keep tightly closed in opaque container. Store away from heat, light, andmoisture.

Section 8 Exposure Controls, Personal Protection

Engineering Controls: Safety shower and eye bath. Mechanical exhaust required.

Exposure Limits: None listed.

OSHA Vacated PELs: None listed for this chemical.

Personal Protective Equipment

Eyes: Wear appropriate protective eyeglasses or chemical safety goggles.

Skin: Wear appropriate protective gloves to prevent skin exposure.

Clothing: Wear appropriate protective clothing to prevent skin exposure.

Respiratory: RequiredGeneral Hygiene Measures: Wash thoroughly after handling.

Ventilation: Required


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Section 9 Physical and Chemical Properties

Physical State: Lyophilized Powder

Appearance: White to Yellow

Odor: Enzyme Odor

pH: N/AVapor pressure: N/A

Vapor density: N/A

Evaporation Rate: N/A

Viscosity: N/A

Boiling Point: N/A

Freezing/Melting Point: N/A

Decomposition Temperature: N/A

Solubility: Immiscible in water

Specific Gravity/Density: N/A

Molecular Formula: N/A

Molecular Weight: N/A

N/A = not available

Section 10 Stability and Reactivity

Chemical Stability: Stable

Conditions to Avoid: Direct sun light, strong acids, strong bases, elevated temperatures.Incompatibilities with Other Materials: Amines, Strong oxidizing agents, chemically

active metals, free radical initiators.

Hazardous Decomposition Products: Carbon Monoxide, Carbon Dioxide

Hazardous Polymerization: May occur.

Section 11 Toxicological Information

Routes of Exposure

Eye: May cause servereye irritation.

Skin: May cause skin irritation.

Ingestion: May be harmful if swallowed.

Inhalation: May be harmful if inhaled. Material may be irritating to mucous membranes

and upper respiratory tract.

Signs and Symptoms of ExposureThe chemical, physical, and toxicological properties have not been fully investigated.

Toxicity Data

No data available


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Section 12 Ecological Information

No information available

Section 13 Disposal Considerations

1. Dispose of waste in accordance with all applicable Federal, State and localregulations.

2. Chemical residues are generally classified as special waste and, as such, thetransportation, storage, treatment and disposal of this waste material must beconducted in compliance with all applicable Federal, State and local regulations.

3. Rinse empty containers thoroughly before disposal and/or recycling.Section 14 Transport Information

Non-hazardous for transport.

Section 15 Regulatory Information

General Information

For research and development use only. Not for drug, household, or other uses.

European/International RegulationsSafety Phrases: S: 22 24/25Do not breathe dust. Avoid contact with skin and eyes.

US Label Text

US Statement: Caution: Avoid contact and inhalation.

United States Regulatory Information

1. Material(s) listed are exempt from the United States Environmental ProtectionAgency Toxic Subs

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