1. Jenna Bilsback,1 Michelle Stolzoff,2 Arthur Gonzales III, 1 Thomas J.Webster1,3
1Northeastern University, Chemical Engineering Department
2Northeastern University, Biological Engineering Department
3Center of Excellence for Advanced Materials Research, King Abudulaziz University, Jeddah, Saudi Arabia

2.  Focus on nanostructured materials for use in
biomedical applications
 106 x smaller then the width of a penny
 Improved cytocompatability of orthopedic implants
 Bacterial and biofilm-resistant material surfaces for
several medical devices
 Catheters
 Endotracheal tubes
 Implants
Scale bar= 500nm
2

3.  Essential micronutrient metalloid
 Cofactor for at least 26 proteins
 Selenium allows for antioxidants to be recycled regularly
 Less reactive oxygen species (ROS) present within the cells
 Chemopreventative and
Chemotherapeutic Properties
 Oxidative stress has been linked to
DNA mutations; a preliminary stage
of cancer
Combs, F. Gerald, Gray P. William, Chemopreventitive Agents: Selenium. Pharmacology and Therapeutics, 1998:79, 179-192.
3

4.  Properties
 Inhibit bacterial growth
 Prevents and treats S. aureus infections2
 Non-cytotoxic to healthy cells1
 Applications
 Used to coat medical devices3
 Cancer therapy
1. Ramos JF, Webster TJ, Int J NanomediciPA, Webster TJ, Int J Nanomedicine, 2011:6, 1553-1558
2. ne, 2012:7, 3907-3914
3. Tran Wang Q, Webster TJ, Journal Biomed Mater Res A, 2012: 100 (12), 3205-3210
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5.  Particles are synthesized through a precipitation
reaction
 Reaction between Glutathione (GSH) and Sodium Selenite
(Na2SeO3) produces particles
 Addition of Sodium Hydroxide (NaOH) precipitates particles
 Addition of deionized water (DiH2O) halts the reaction
5

6. Volume GSH
Volume Na2SeO3
Time 1 Time 2
NaOH
Number of Samples
6
Reaction

7. 7
 Precise and repeatable coverage
 Use an experimental design program to
produce a central composite design (CCD)
model
 Characterize resulting surface coatings
 Verify the fit and predictability of the CCD
model

8.  Previous experimental data
 SeNP coverage is related to time parameters
 Different reactant: substrate area ratios may alter
coverage 8
0 s 5 s
30 s60 s

9.  Time
 T1: Reaction (GSH+Na2SeO3)
 T2: Precipitation (NaOH before rinsing with dIH2O)
 Volume of GSH, Na2SeO3, and NaOH
 Constant 4:1 molar ratio of GSH:Na2SeO3, with a final concentration of 80 μM NaOH
 Substrate surface area
 Number of samples per reaction
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10.  Create a relationship between a response
variable and a set of design factors
 Accounts for:
 Statistical experimental design fundamentals
 Regression modeling techniques
 Optimization methods
 Reduces required experiments for meaningful
results
10

11.  SeNP Coverage (SEM)
 Number of nanoparticles bound to substrate
 Nanoparticle diameter
 Analyzed via ImageJ
Scale bar 2000 nm
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12.  Quadratic model predicting coverage fits
with an r2=.8766
 “Lack of fit” is not significant, suggesting a
feasible predictive ability
 Specific SeNP coverage can thus be produced
with set parameters.
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13.  A longer time increment, in both instances, increases the
number of bound nanoparticles
 All below runs had reactant volumes of 2.41 mL
Scale bars: 2000 nm
Run 4
T1=16.15 sec
T2=16.15 sec
5 Samples
Run 5
T1=48.855 sec
T2=16.15 sec
2 Samples
Run 27
T1=16.15 sec
T2=48.85 sec
5 Samples
Run 12
T1=48.85 sec
T2=48.85 sec
2 Samples
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14. 14

15.  Volume shows noticeable differences at lower amounts with
smaller changes as the volume increases
 Suggests existence of a saturation point
▪ All below runs were ran with two substrate sections and were reacted for the same time increments in
both cases (32.5 seconds)
▪ Scale bars: 2000 nm
Run 19
Volume:
2.00 mL
15
Run 18
Volume:
3.00 mL
Run 36
Volume:
4.00 mL

16.  Volume shows noticeable differences at lower
amounts then tapers off as the volume increases
 Suggests existence of a saturation point
▪ All below runs were ran with two substrate sections and were reacted for the same
time increments in both cases (32.5 seconds)
16

17.  No significant contribution to changes in
coverage (p > 0.05)
 T1=16.15 s,T2 = 48.85 s,V= 2.41 ml
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2 samples 5 samples

18.  A quadratic CCD model can be used to describe the
coating of SeNP on polymer substrates
 Time appears to have a larger effect than volume on
the samples
 Coverage was the only response with significant
correlations with parameter changes
 Nanoparticle size was not greatly affected
 Real test will be to use the model to predict coverage
of samples
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19.  Thomas J.Webster, Ph.D.
 Michelle Stolzoff , M.S.
 Arthur Gonzales III, M.S.
 Webster Nanomedicine lab
 Bill Fowle (SEM)
 Dean Richard Harris
 Northeastern University and the Chemical Engineering
Department
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20. 20

21. Response 2 Coverage
ANOVA for Response Surface
Quadratic Model
Analysis of variance table [Partial
sum of squares - Type III]
Sum of Mean F p-value
Source Squares df Square Value Prob > F
Model 1911.094429 13 147.0072638 14.21039307 < 0.0001 significant
A-time 1 925.4719397 1 925.4719397 89.4603416 < 0.0001
B-time 2 76.58456958 1 76.58456958 7.403014032 0.0115
C-Volume 357.0034287 1 357.0034287 34.5095808 < 0.0001
D-Number of Sample 19.29281907 1 19.29281907 1.864931945 0.1838
AB 180.6624972 1 180.6624972 17.46366153 0.0003
AC 0.670065031 1 0.670065031 0.064771544 0.8011
AD 1.558083928 1 1.558083928 0.150611504 0.7011
BC 17.29374603 1 17.29374603 1.671692421 0.2074
BD 157.0163379 1 157.0163379 15.17791586 0.0006
CD 61.97605672 1 61.97605672 5.990888505 0.0214
A^2 42.00539534 1 42.00539534 4.060433228 0.0543
B^2 35.15144196 1 35.15144196 3.397898813 0.0767
C^2 29.68990997 1 29.68990997 2.869962204 0.1022
Residual 268.9713677 26 10.3450526
Lack of Fit 200.5892147 16 12.53682592 1.833347648 0.1665 not significant
Pure Error 68.38215291 10 6.838215291 21

22.  Final Equation in Terms of Actual Factors:
Number of Sample 2
Coverage =
 +9.38622
 -0.42404 * time 1
+0.13690 * time 2
-5.83949 * Volume
+0.012568 * time 1 * time 2
+0.021048 * time 1 * Volume
-0.10693 * time 2 * Volume
+4.52037E-003 * time 12
-4.13517E-003 * time 22
+2.87403 * Volume2
Number of Sample 5
Coverage =
+12.71113
-0.39483 * time 1
+0.43016 * time 2
-10.90617 * Volume
+0.012568 * time 1 * time 2
+0.021048 * time 1 * Volume
-0.10693 * time 2 * Volume
+4.52037E-003 * time 12
-4.13517E-003 * time 22
+2.87403 * Volume2
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23.  Higher atomic number of Se
shows brighter on SEM (scale
bar = 500 nm)
 EDAX measurements show clear
Se peaks
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24. 24

25.  Humans typically have 13-20 mg of Se in their
bodies
 Toxic at 15 ug/kg, but 400 ug per day is a
“tolerable intake level”
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