NE 301 Lec 1 Sensors Notes
Transcript of NE 301 Lec 1 Sensors Notes
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 1/20
1B(NE102)Module1: NanomaterialsHealthRisk
Assessment
HazardIden*fica*on,RiskAssessment,Exposure
Assessment;ExternalandInternalDose;ReferenceDose;HazardIndex;Life*meCancerRisk;
2A(Ne201)Module2: Nanotoxicology
ADME;Inhala*onEffectsandTransloca*on;DermalEffects;Oxida*veStress;Cytotoxicity;Neurotoxicity;
Genotoxicity,MutagenicityandCancer;
PreviousMilestoneLectures
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 2/20
2B(NE202)Module3:
NanomaterialsExposureAssessmentand
Ecotoxicology
Howtoprotectyourself :Occupa*onalExposure
Assessment;Sampling;Nanometrics;masks/gloves
Howtoprotecttheenvironment :Environmental
FateandTransportProcesses,Ecotoxicology;
Aqua*cToxicology;Biopersistence;
Biomagnifica*on;
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
PreviousMilestoneLectures
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 3/20
3AModule4: NanomaterialsConsumerProducts
Whatdoweknowaboutthenanostuffoutthere?
SensorsandScreening;Sensi*vityandSpecificity;
Posi*ve/Nega*vePredic*veValues;ConsumerProducts(TiO2,Ag,CNT…);ConsumerExposureand
diseaserisks;Cosme*cs;ProductLifeCycleanalysis
3BModule5: NanomaterialsRisksandBenefits
Howwouldyouknowifitaffec;nghumans?
Epidemiology;Howtocomparedifferenthuman
groups;Rela*verisksandOddsra*os;Confounding;
Eng.andnon-engineeredUltrafines;DieselExhaust;
Current/FutureMilestoneLectures
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 4/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Using Nanoparticles:
Making and Understanding Sensors and
Medical Screening Devices
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 5/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Cash2010TrendsMolec.Med.16:584
BETTER SENSORS: CNT and Diabetes
Nanodevices are beingproposed as better
alternative to current
sensors:
Based on redox active
CNT/metal/metal oxide
electrode: enzymatic redox
conversion of glucose
Current sensors suffer from
limited lifetime immune
response to sensor.
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 6/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
NEW SENSORS: Gold and Cancer
Bind volatile organic compounds that are knownmarkers for cancer; based on chemoresistance
Au particles show different
patters from healthy and
lung cancer patients
Mazzone2009NatureNanotech4:621
DrHaickChemEng.NanotechInst,Ben-GurionUniv.,Israel
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 7/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Thiol-capped
5 nm Au particles
~ 75% effectiveness
at catching those
with lung tumors
~ 25% falsenegative rate
…what is impact
of false negative?Peng2009Nature
Nanotech4:669
Healthy
Lung Cancer
Analysis by
GCMS
HS-CH2-CH2-R
NEW SENSORS: Gold and Cancer
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 8/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
When you compare your test (or device) toanother (say industry standard) or to the actual
state of patients, there are two important testresults; Sensitivity and Specificity
Comparing your test to the ‘real’ answer
Disease State or
standard test
+ -
# your
sensor
+
-
true +
false -
false +
true -
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 9/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Sensitivity : is the probability that a test result ispositive when administered to someone who has
the disease.
SEN =
Comparing your test to the ‘real’ answer
+ -
# your
sensor
+
-
true +
false -
false +
true -
Disease State or
standard test
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 10/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Comparing your test to the ‘real’ answer
Specificity: is the probability that a test result is
negative when administered to someone who does
not have the disease.
SPEC =
+ -
# your
sensor
+
-
true +
false -
false +
true -
Disease State or
standard test
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 11/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Low sensitivity could mean that:
_______________________________________
Low specificity would mean that:
_______________________________________
+ -
# your
sensor
+
-
true +
false -
false +
true -
Which is
more
important,sensitivity or
specificity?
Comparing your test to the ‘real’ answer
Disease State or standard test
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 12/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Comparing your test to the ‘real’ answer
Standard Yours1. - +
2. + +
3. - -4. + +
5. - -
6. + +
7. - -8. - -
9. - +
10. + -
You make a device to testfor a disease and compare
your test to the currently
used standard. 10 samples
compare the tests.
What is the sensitivity and
specificity for your device?
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 13/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
When you are handed a positive test, what you
want to know is whether it is real…
Positive Predictive Value PPV : the probability
that a person with a positive result actually has the
disease.
PPV = _______________
# Disease State+ -
# your
sensor
+
-
true +
false -
false +
true -
What if they told you your test was positive?
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 14/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
When you are handed a negative test, what you
want to know is whether it is real…
Negative Predictive Value NPV: the probability
that a person with a negative result actually has no
disease.
NPV = ___________
# Disease State+ -
# your
sensor
+
-
true +
false -
false +
true -
What if they told you your test was negative?
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 15/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
About Sensors: Specific Example HIV
You’ve made a sensor for HIV
It is used on 100,000 people. Of the 500 HIV-
positive people, 475 tested positive, and of the
HIV-negative group, 94,525 tested negative.
Determine the sensitivity, specificity, positive-
predictive and negative-predictive values.
What’s going on with the +’ve pred. value?
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 16/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
About Sensors: Specific Example HIV
Generally, if prevalence is low, PPV is also low.
Low PPV means lots of False Positives:
False positives: Type I errors:
- you rejected the null hypothesis when the null
hypothesis was true. You accused the wrong guy…
False negatives: Type II errors:- failure to reject the null hypothesis when the null
hypothesis is true. You let the bad guy go…
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 17/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
About Sensors: ELISA HIV
HIV antigen protein on a surface reacts with antibodies
in blood from someone infected with HIV. Antibodies
are enzyme linked for detection.
High sensitivity: even low levels of antibody detected.Some people without HIV will still have non-specific
binding (other antibodies) that leads to some
fluorescence: what is cutoff ? Lower specificity.
HIV test measuring fluorescence
from HIV antibody in enzyme-linked
immunosorbent assay (ELISA).
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 18/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
Op*caldensityra*o(fluorescenceintensity)
#people
HIV-free withHIV
ABC
A,B,C: cutoffs in optical density to separate positive
(high density) from negative (low density) result.
About Sensors: ELISA HIV
A: large number of false-positives, no FN
B: lower FP but now also FNC: no FP, but high FN
Forinfec*ous
diseases,choosenoFN;thenretest
allposi*ves
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 19/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
About Sensors: Western Blot
1 .Gel electropheresis separates out byelectropheretic mobility blood proteins and looks
for HIV proteins.
2. Proteins are moved from gel into separate
membrane by ‘blotting ’, by capillary action.
3. Expensive human antibodies are used to bind to
the HIV proteins.
4. Antibody is linked to fluorescent enzyme that isactivated upon binding.
Antibodies are very structure specific, wrong binding
does not occur; No false positives: High spec.
7/31/2019 NE 301 Lec 1 Sensors Notes
http://slidepdf.com/reader/full/ne-301-lec-1-sensors-notes 20/20
UniversityofWaterloo;NanomaterialHealthRiskMilestone;Dr.L.Deakin
ELISA
TP + FP TN (no FN)
WESTERNBLOT
TP (no FP)
+ -
+ -
TN (+ FN)
HIGHSEN:strongbinding
HIGHSPEC:specificbinding
HIV: Run the Cheap Sensor First