<s>
An	O
ion-sensitive	B-Algorithm
field-effect	I-Algorithm
transistor	I-Algorithm
(	O
ISFET	B-Algorithm
)	O
is	O
a	O
field-effect	O
transistor	B-Application
used	O
for	O
measuring	O
ion	O
concentrations	O
in	O
solution	O
;	O
when	O
the	O
ion	O
concentration	O
(	O
such	O
as	O
H+	O
,	O
see	O
pH	O
scale	O
)	O
changes	O
,	O
the	O
current	O
through	O
the	O
transistor	B-Application
will	O
change	O
accordingly	O
.	O
</s>
<s>
It	O
is	O
a	O
special	O
type	O
of	O
MOSFET	B-Architecture
(	O
metal	B-Architecture
–	I-Architecture
oxide	I-Architecture
–	I-Architecture
semiconductor	I-Architecture
field-effect	I-Architecture
transistor	I-Architecture
)	O
,	O
and	O
shares	O
the	O
same	O
basic	O
structure	O
,	O
but	O
with	O
the	O
metal	B-Algorithm
gate	I-Algorithm
replaced	O
by	O
an	O
ion-sensitive	O
membrane	O
,	O
electrolyte	O
solution	O
and	O
reference	O
electrode	O
.	O
</s>
<s>
Invented	O
in	O
1970	O
,	O
the	O
ISFET	B-Algorithm
was	O
the	O
first	O
biosensor	O
FET	O
(	O
BioFET	O
)	O
.	O
</s>
<s>
An	O
ISFET	B-Algorithm
's	O
source	O
and	O
drain	O
are	O
constructed	O
as	O
for	O
a	O
MOSFET	B-Architecture
.	O
</s>
<s>
An	O
ISFET	B-Algorithm
's	O
threshold	O
voltage	O
depends	O
on	O
the	O
pH	O
of	O
the	O
substance	O
in	O
contact	O
with	O
its	O
ion-sensitive	O
barrier	O
.	O
</s>
<s>
An	O
ISFET	B-Algorithm
electrode	I-Algorithm
sensitive	O
to	O
H+	O
concentration	O
can	O
be	O
used	O
as	O
a	O
conventional	O
glass	O
electrode	O
to	O
measure	O
the	O
pH	O
of	O
a	O
solution	O
.	O
</s>
<s>
A	O
too	O
large	O
volume	O
constrained	O
by	O
a	O
classical	O
reference	O
electrode	O
also	O
precludes	O
the	O
miniaturization	O
of	O
the	O
ISFET	B-Algorithm
electrode	I-Algorithm
,	O
a	O
mandatory	O
feature	O
for	O
some	O
biological	O
or	O
in	O
vivo	O
clinical	O
analyses	O
(	O
disposable	O
mini-catheter	O
pH	O
probe	O
)	O
.	O
</s>
<s>
For	O
this	O
reason	O
,	O
since	O
more	O
than	O
20	O
years	O
many	O
research	O
efforts	O
have	O
been	O
dedicated	O
to	O
on-chip	O
embedded	O
tiny	O
reference	O
field	O
effect	O
transistors	B-Application
(	O
REFET	O
)	O
.	O
</s>
<s>
A	O
crucial	O
factor	O
for	O
ISFET	B-Algorithm
electrodes	I-Algorithm
,	O
as	O
for	O
conventional	O
glass	O
electrodes	O
,	O
remains	O
thus	O
the	O
reference	O
electrode	O
.	O
</s>
<s>
For	O
ISFET-based	O
sensors	O
,	O
low-frequency	O
noise	O
is	O
most	O
detrimental	O
to	O
the	O
overall	O
SNR	O
as	O
it	O
can	O
interfere	O
with	O
biomedical	O
signals	O
which	O
span	O
in	O
the	O
same	O
frequency	O
domain	O
.	O
</s>
<s>
The	O
noise	O
sources	O
outside	O
the	O
ISFET	B-Algorithm
itself	O
are	O
referred	O
to	O
as	O
the	O
external	O
noise	O
,	O
such	O
as	O
environmental	O
interference	O
and	O
instrument	O
noise	O
from	O
terminal	O
read-out	O
circuits	O
.	O
</s>
<s>
The	O
intrinsic	O
noise	O
refers	O
to	O
that	O
appearing	O
in	O
the	O
solid	O
part	O
of	O
an	O
ISFET	B-Algorithm
,	O
which	O
is	O
mainly	O
caused	O
by	O
the	O
trapping	O
and	O
de-trapping	O
of	O
carriers	O
at	O
the	O
Oxide/Si	O
interface	O
.	O
</s>
<s>
Many	O
methods	O
are	O
invented	O
to	O
suppress	O
the	O
noise	O
of	O
ISFET	B-Algorithm
.	O
</s>
<s>
For	O
example	O
,	O
to	O
suppress	O
the	O
external	O
noise	O
,	O
we	O
can	O
integrate	O
a	O
bipolar	O
junction	O
transistor	B-Application
with	O
ISFET	B-Algorithm
to	O
realize	O
immediate	O
the	O
internal	O
amplification	O
of	O
drain	O
current	O
.	O
</s>
<s>
The	O
basis	O
for	O
the	O
ISFET	B-Algorithm
is	O
the	O
MOSFET	B-Architecture
.	O
</s>
<s>
Dutch	O
engineer	O
Piet	O
Bergveld	O
,	O
at	O
the	O
University	O
of	O
Twente	O
studied	O
the	O
MOSFET	B-Architecture
and	O
realized	O
it	O
could	O
be	O
adapted	O
into	O
a	O
sensor	O
for	O
electrochemical	O
and	O
biological	O
applications	O
.	O
</s>
<s>
This	O
led	O
to	O
Bergveld	O
's	O
invention	O
of	O
the	O
ISFET	B-Algorithm
in	O
1970	O
.	O
</s>
<s>
He	O
described	O
the	O
ISFET	B-Algorithm
as	O
"	O
a	O
special	O
type	O
of	O
MOSFET	B-Architecture
with	O
a	O
gate	O
at	O
a	O
certain	O
distance	O
"	O
.	O
</s>
<s>
ISFET	B-Algorithm
sensors	O
could	O
be	O
implemented	O
in	O
integrated	O
circuits	O
based	O
on	O
CMOS	B-Device
(	O
complementary	O
MOS	O
)	O
technology	O
.	O
</s>
<s>
ISFET	B-Algorithm
devices	O
are	O
widely	O
used	O
in	O
biomedical	O
applications	O
,	O
such	O
as	O
the	O
detection	O
of	O
DNA	O
hybridization	O
,	O
biomarker	O
detection	O
from	O
blood	O
,	O
antibody	O
detection	O
,	O
glucose	O
measurement	O
and	O
pH	O
sensing	O
.	O
</s>
<s>
The	O
ISFET	B-Algorithm
is	O
also	O
the	O
basis	O
for	O
later	O
BioFETs	O
,	O
such	O
as	O
the	O
DNA	O
field-effect	O
transistor	B-Application
(	O
DNAFET	O
)	O
,	O
used	O
in	O
genetic	O
technology	O
.	O
</s>
