J. A

m. C

hem

. Soc

.

Pla

smo

n v

s. m

irro

r

E. K

rets

chm

ann, Z. Ph

ys.

1971

Roth

enhäu

sler

et

al.,N

ature

1988

Wils

on, Sc

ience

2002

Su

rface

Pla

smo

n R

eso

nan

ce (

SPR

): C

on

cep

t

E. K

rets

chm

ann, Z. Ph

ys.

1971

Roth

enhäu

sler

et

al.,N

ature

1988

Wils

on, Sc

ience

2002

Su

rface

Pla

smo

n R

eso

nan

ce (

SPR

): C

on

cep

t

Gla

ssA

ir

Gla

ss

Air

Gold

Gold

Su

rface

Pla

smo

n R

eso

nan

ce (

SPR

): C

on

cep

t

Fie

ld l

oca

lizati

on

in

th

e z

dir

ect

ion

Kre

tsch

man

n

con

fig

ura

tio

nD

isp

ers

ion

rela

tio

n

SPR

co

nd

itio

n :

Ksp

= K

dx

Su

rface

Pla

smo

n R

eso

nan

ce (

SPR

): C

on

cep

tLab

el-fr

ee B

io-s

en

sin

g U

sin

g S

PR

(1)

(

2) (

3)

Angle

(1)

Bare

Go

ld

(2)

Sin

gle

str

an

ded

DN

A

imm

ob

iliz

ed

(3)

Hyb

rid

ized

wit

h t

he

com

ple

men

tary

str

an

d

•D

NA

chip

•Pr

ote

in c

hip

•C

ell/

tiss

ue

chip

htt

p:/

/ww

w.t

issu

e-ar

ray.

com

Mark

et

Sh

are

of

Wo

rld

wid

e M

ed

ical

Sen

sor

Majo

r Bio

sen

sor

Co

mp

an

ies

Majo

r SPR

Bio

sen

sor

Co

mp

an

ies

(1)

Majo

r SPR

Bio

sen

sor

Co

mp

an

ies

(2)

Rece

nt

SPR

Bio

sen

sors

Bia

Co

re (

Sw

ed

en

)

Bia

Co

re S

en

sor

Ch

ip

Sp

reet

a

Texas

Inst

rum

en

ts (

U.S

.)

SP

R I

mag

er

•TTh

ickn

ess

sens

itiv

ity

: 1 Å

•SS

cann

ing

met

hod

: Det

ecto

r ro

tatin

g st

age

•SS

pect

ral r

ange

: 6

00

-1

10

0 n

m

•IIn

cide

nt A

ngle

ran

ge :

40

-7

0 d

eg (f

or d

iffe

rent

pri

sm)

•HH

igh

sens

itiv

ity

Nea

r IR

CC

D d

etec

tor

GW

C T

ech

no

log

ies

(U.S

.)H

TS B

iosy

stem

s (U

.S.)

HT

S B

iosy

stem

s Sen

sor

Ch

ipA

ffin

ity S

en

sors

(U

.K.)

K-M

AC

(K

ore

a)

1mg/

ml

0.75

mg/

ml

0.5m

g/m

l

0.25

mg/

ml

0.1m

g/m

l

0.07

5mg/

ml

0.05

mg/

ml

0.02

5mg/

ml

0.01

mg/

ml

Con

trol-

1mg/

ml B

SA

SP

R I

mag

ing

Sys

tem

KR

IBB +

K-M

AC

(K

ore

a)

RSl

avik

et a

lSe

nsor

s and

Act

uato

rs B

Fib

er-

base

d S

PR

Co

mm

erc

ial

SPR

Syst

em

s (O

utd

ate

d)

SPR

In

terr

og

ati

on

Meth

od

s (1

)

Pri

sm

Pri

sm

Met

al L

ayer

Met

al L

ayer

Ana

lyte

Ana

lyte

SPR

In

terr

og

ati

on

Meth

od

s (2

)

Pri

sm

Met

al L

ayer

Ana

lyte

Surf

ace

Plas

mon R

esonan

ce v

s. M

etal

Str

uct

ure

=42.5

glass

titanium

gold

air

•SP

R is

extr

emel

y se

nsi

tive

to t

he

mat

eria

l an

d s

truct

ure

of

met

al.

glass

titanium=1nm

gold=49nm

air

•W

avel

ength

inte

rrogat

ion is

less

sen

siti

ve,

but

easi

er t

o d

etec

t SP

R.

•A

ngula

r in

terr

ogat

ion r

equir

es m

echan

ical

move

men

t.•

Elec

tronic

inte

rrogat

ion ?

Surf

ace

Plas

mon R

esonan

ce:

Inte

rrogat

ion

Met

hods

•Po

rtab

ility

•M

ult

iple

xin

g

•Se

nsi

tivi

ty

•Sp

atia

lR

esolu

tion

(x-y

and

z)

•In

vest

igat

ion

of

Wid

erR

ange

of

Inte

ract

ions

i.e.

cel

l su

rfac

e in

tera

ctio

ns

New

Dir

ect

ion

s fo

r SPR

Bio

sen

sor

Rese

arc

h

Tex

asIn

stru

men

ts:Sp

reet

aC

hin

ow

sky

etal.

Sens.

Act

uat

ors

B2003

Mult

i-C

han

nel

Senso

rC

hip

-Bi

aCore

SPR

Imag

ing

-G

WC

Tec

hnolo

gie

s-

IBIS

Tec

hnolo

gie

s-

Gra

ffin

ity

-K

MA

C

New

Dir

ect

ion

s fo

r SPR

Bio

sen

sor

Rese

arc

h

•Po

rtab

ility

•M

ult

iple

xin

gfo

rH

igh-T

hro

ughput

Scre

enin

g

New

Dir

ect

ion

s fo

r SPR

Bio

sen

sor

Rese

arc

h

•In

vest

igat

ion

of

Wid

erR

ange

of

Inte

ract

ions

i.e.

cel

l su

rfac

e in

tera

ctio

ns

Hid

e et

al. A

nal

. Bi

och

em. 2002

Fang e

t al

. A

nal

. C

hem

. 2005

Invest

igati

on

of

Cell

Su

rface

In

tera

ctio

ns

Baacetal.Biotechnol.Bioeng.2006

AcM

NPV

infe

cted

Hel

ioth

is V

ires

cens

larv

ae

Hel

ioth

is V

ires

cens

host

Bacu

lovi

rus

or

Auto

gra

pha c

alif

ornic

a m

ult

iple

nucl

ear

poly

hed

rosi

s vi

rus

(AcM

NPV

)

Bio

med

ical

ap

pli

cati

on

s o

f p

lasm

on

ics

•In

vest

igat

ion

of

cell

surf

ace

inte

ract

ions

Hoff

man

et

al. J.

His

toch

em.

Cyt

och

em. 1999

Hid

e et

al. A

nal

. Bi

och

em. 2002

Bio

med

ical

ap

pli

cati

on

s o

f p

lasm

on

ics

•In

vest

igat

ion

of

cell

surf

ace

inte

ract

ions

Gie

bel

et

al. Bi

ophys

. J.

1999

Ap

pro

ach

es

to E

nh

an

ced

Dete

ctio

n S

en

siti

vit

y

•In

crea

seof

opti

calpow

erby

5ti

mes

•In

crea

seof

angula

rre

solu

tion

by

2ti

mes

•In

crea

seof

det

ecto

rse

nsi

tivi

tyby

2ti

mes

•D

iffr

acti

on-lim

ited

spots

:1

0x

10

um

2

•In

crea

seof

sensi

tivi

tyusi

ng

LSPR

by

10

tim

es

Sen

siti

vit

y e

nh

an

cem

en

t u

sin

g n

an

op

lasm

on

ics

Fir

st-o

rder

est

imati

on

(op

tim

isti

csc

en

ari

o!)

SPR

Sen

sors

: Sen

siti

vit

y L

imit

s

Evo

luti

on

of

SPR

Sen

sors

•C

har

ge

den

sity

osc

illat

ions

confi

ned

in m

etal

lic n

anost

ruct

ure

s

•En

han

cem

ent

of

loca

l el

ectr

om

agnet

ic f

ield

s

•St

rong lig

ht

scat

teri

ng a

nd inte

nse

lig

ht-

abso

rpti

on b

and

•N

oble

met

als

for

bio

com

pat

ibili

ty

•Ea

se o

f fu

nct

ional

izat

ion

•D

epen

den

t on t

he

size

, sh

ape,

and lat

tice

spac

ing o

f th

e nan

ost

ruct

ure

as

wel

l as

the

die

lect

ric

funct

ions

of

the

surr

oundin

g e

nvi

ronm

ents

.

Lo

cali

zed

su

rface

pla

smo

ns

(LSPs)

Sen

siti

vit

y E

nh

an

cem

en

t o

f SPR

: Lo

cali

zed

SPR

Will

ets

et a

l., A

nnu.

Rev

. Phy

s. C

hem

. 58

, 201

2G

ram

otne

vet

al.,

Nat

. P

hoto

n. 8

, 201

4K

elly

et a

l., J

. Phy

s. C

hem

. B 1

07, 2

003

Talle

y et

al.,

Nan

o Le

tt. 5

, 201

2H

alla

s et

al.,

Che

m. R

ev. 1

11, 2

011

Nor

dlan

dere

t al.,

Nan

o Le

tt. 4

, 200

4

•A

mplif

icat

ion

of

opti

calsi

gnat

ure

s

•In

crea

sed

effe

ctiv

esu

rfac

ear

ea

•C

olo

caliz

eddet

ecti

on

•M

ult

imodal

com

bin

atio

n

•O

ther

appro

aches

i.e.

phas

e det

ecti

on

Sen

siti

vit

y e

nh

an

cem

en

t o

f SPR

bio

sen

sors

SPR

Bio

sen

sors

Co

up

led

wit

h N

an

op

art

icle

s (1

)

•Lo

caliz

edsu

rfac

epla

smon

pro

duce

dat

nan

opar

ticl

eskn

ow

nto

amplif

yse

nsi

tivi

tyof

SPR

~0

.1pg/m

m2

(A)

12

-mer

oli

go

nu

cleo

tid

e

(B)

Hyb

rid

ized

wit

h t

he

com

ple

men

tary

24

-mer

oli

go

nu

cleo

tid

e

(C)

Hyb

rid

ized

wit

h t

he

Au

-part

icle

tag

ged

co

mp

lem

en

tary

12

-mer

oli

go

nu

cleo

tid

eH

e et

al.

JAC

S 2

00

0

Lyon e

t al.

Anal

. C

hem

. 1998

Muci

c et

al.

JAC

S 1

99

8H

aes

et.

al.

JAC

S2

00

2

Ag

Gla

ss

Gla

ssA

g

stre

pta

vidin

Gla

ssA

g

stre

pta

vidin

(A)

Bio

tin

yla

ted

A

g n

an

op

art

icle

s

(B)

Mo

dif

ied

wit

hst

rep

tavid

in

(C)

Mo

dif

ied

wit

hb

ioti

nyla

ted

coll

oid

al

Au

n

an

op

art

icle

s

SPR

Bio

sen

sors

Co

up

led

wit

h N

an

op

art

icle

s (2

)

•Fu

rther

sensi

tivi

tygai

nm

aybe

obta

ined

by

opti

miz

ing

the

size

,sh

ape,

and

geo

met

ryof

the

nan

opar

ticl

e/

nan

ow

ire.

e.g.G

ots

chy

etal

.O

pt.

Lett

.1

99

6

Lyon

etal

.J.

Phys

.C

hem

.B

1999

Pile

etal

.O

pt.

Lett

.2004

Byun

etal

.O

pt.

Expre

ss2

00

5

•N

anopar

ticl

ebas

edw

aveg

uid

ee.

g.

Mai

eret

al.

Nat

ure

Mat

eria

ls2003

tran

smis

sion

loss

:6

dB/

m,

pro

pag

atio

ndis

tance

:~

0.5

m

Fluore

scen

t nan

osp

her

e

Ag n

anopar

ticl

es

Fiber

-tip

SPR

Bio

sen

sors

Co

up

led

wit

h N

an

op

art

icle

s (3

)LSPR

Bio

sen

sors

Usi

ng

Nan

op

art

icle

s

•N

an

op

art

icle

s o

ften

ag

gre

gate

du

rin

g s

yn

thesi

s,

esp

eci

all

y a

t h

igh

co

nce

ntr

ati

on

.

•Syn

thesi

s an

d a

pp

lica

tio

n p

roce

sses

aff

ect

re

pro

du

cib

ilit

y.

Adva

nta

ges

•H

igh s

ensi

tivi

ty induce

d b

y LS

Ps e

xci

ted o

f gold

nan

ow

ires

•R

elia

ble

and r

epro

duci

ble

per

form

ance

•C

ust

om

ized

des

ign t

o m

eet

a sp

ecif

ic s

ensi

tivi

ty r

equir

emen

t

LSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

SPR

in

a n

an

ost

ruct

ure

SPR

+ n

an

o =

nan

op

lasm

on

ics

Fie

ld l

oca

lizati

on

in

th

e x

/y d

irect

ion

bc

SPR

in

a n

an

ost

ruct

ure

Ho

t sp

ots

: en

han

ced

fie

lds

Incr

ease

of

surf

ace

are

a

bc

Ho

t sp

ot

Mo

lecu

lar

sen

siti

vit

y

en

han

cem

en

t

Eff

ect

ive m

ed

ium

th

eo

ry f

or

nan

op

lasm

on

ics

A h

om

og

en

eo

us

eff

ect

ive m

ed

ium

may s

imp

lify

n

an

op

lasm

on

ic f

ield

s.

An

(inhom

ogen

eous)

dif

frac

tion

gra

ting

wit

ha

per

iod

<<

,fi

ll-fa

ctor

f,an

dA

and

Bfo

rth

eper

mit

tivi

ties

of

the

gra

ting

mat

eria

lsth

atm

ake

adif

frac

tion

gra

ting

can

be

appro

xim

ated

asa

(hom

ogen

eous)

anis

otr

opic

med

ium

such

that

its

effe

ctiv

eper

mit

tivi

tyis

giv

enby

TETM

BA

TMTM

eff

BA

TETE

eff

ff

ff

S.M

.R

ytov,

“Ele

ctro

mag

net

icp

roper

ties

of

afi

nel

yst

rati

fied

med

ium

,”So

v.Ph

ys.

JET

P2,466-4

75

(1956)

For

the

effe

ctiv

em

ediu

mth

eory

tobe

valid

,fo

llow

ing

condit

ions

should

be

met

:[1

]only

the

zero

th-o

rder

spro

pag

ate

inth

em

ediu

m,

[2]

only

one

mode

pro

pag

ates

inth

egra

ting,

and

[3]

the

gra

ting

dep

this

larg

een

ough

such

that

the

evan

esce

nt

modes

crea

ted

atth

eto

pan

db

ott

om

gra

ting

inte

rfac

esm

aynot

tunnel

thro

ugh.

Eff

ect

ive m

ed

ium

th

eo

ry f

or

nan

op

lasm

on

ics

Eff

ect

ive m

ed

ium

th

eo

ry, w

hil

e p

resu

mab

ly

eff

icie

nt

[1][

2], v

ali

d f

or

nan

op

lasm

on

ics[

3]?

Eff

ect

ive m

ed

ium

th

eo

ry f

or

nan

op

lasm

on

ics

•Seco

nd

-ord

er

eff

ect

ive m

ed

ium

th

eo

ry s

eem

s to

re

pre

sen

t n

an

op

lasm

on

ic f

ield

s.•

Mo

re c

om

pre

hen

sive s

tud

y n

eed

ed

.

bc

a

SPR

SPR

NW

SPR

NW

SPR

SPR

NW

SPR

SEFLSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

Byun

etal.Opt.Express2005

Byun

etal.Sens.ActuatorsB2006

LSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

Nan

ow

ire-b

ase

d L

SPR

bio

sen

sors

: d

esi

gn

MM

DM

MD

spp

nn

cwn

k

DM

DM

spp

cwk

Effe

ctiv

eM

Effe

ctiv

eM

k spp

LSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

LSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

LSPR

Bio

sen

sors

Usi

ng

Nan

ow

ires

Nan

ow

ire-b

ase

d L

SPR

bio

sen

sors

: d

esi

gn

En

han

cem

en

t w

ith

a T

-pro

file

is

deem

ed

ass

oci

ate

d w

ith

•V

ert

ex

•LSP i

sola

tio

n f

rom

bu

lk S

P

Sen

siti

vit

y e

nh

an

cem

en

t u

sin

g n

an

op

lasm

on

ics

Byun e

t al

. O

pt.

Let

t. 2

00

7

Sen

siti

vit

y e

nh

an

cem

en

t u

sin

g n

an

op

lasm

on

ics

31

% e

nhan

cem

ent

44

% e

nhan

cem

ent

•Su

rface

-lim

ited

•Pla

smo

nic

fie

ld a

mp

lifi

cati

on

?!

Sen

siti

vit

y e

nh

an

cem

en

t u

sin

g n

an

op

lasm

on

ics

Sen

siti

vit

y d

eg

rad

ati

on

du

e t

o s

urf

ace

ro

ug

hn

ess

Calc

ula

tio

n f

or

3-n

m t

hic

k H

DT

-SA

M

SPR

Dete

ctio

n o

f a S

AM

En

han

ced

SPR

on

Nan

ost

ruct

ure

s

En

han

ced

SPR

on

Nan

ost

ruct

ure

s

x

n p

I. A

bdul

halim

, “B

iose

nsin

g co

nfig

urat

ions

usi

ng g

uide

d w

ave

reso

nant

stru

ctur

es,”

Opt

ical

Wav

egui

de S

ensi

ng a

nd Im

agin

g (S

prin

ger-V

erla

g, 2

007)

, pp.

211

–228

.S

hala

bney

et a

l. La

ser P

hoto

n. R

ev. (

2011

)W

. Lee

and

D. K

im, J

. Opt

. Soc

. Am

. A (2

012)

x

y

A. S

hala

bney

et. a

l, S

ens.

Act

uato

rs A

, 201

0

Overl

ap

In

teg

ral

Targ

et

Co

loca

lizati

on

Targ

et

Co

loca

lizati

on

on

Die

lect

ric

Su

rface

Targ

et

Co

loca

lizati

on

wit

h 3

D N

an

oarr

ays

Co

loca

lizati

on

by p

lasm

on

lit

ho

gra

ph

y

L

En

han

ced

SPR

on

Nan

ost

ruct

ure

sPla

smo

nic

Mu

ltim

od

ali

ty w

ith

Mic

roca

vit

y

SPR

-SP C

ou

ple

d F

luo

resc

en

ce

Ekg

asi

t et

al. A

nal. C

hem

., 2

00

4