MICROBIVORES

Sem!nar report Submitted !n fulfilment of the requirement for the degree of

Bachelor of Technology in Electron!cs and Telecommunication Engineering

SCHOOL OF ELECTRON!CS ENG!NEER!NG

KALINGA INSTITUTE OF INDUSTRIAL TECHNOLOGY
DEEMED TO BE UNIVERSITY , BHUBANESWAR

SUBMITTED TO
Prof N.K. ROUT

SUBMITTED BY
AASTHA SINGH
1504077
ETC-2

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 @CKNOWLEDGEMENT
F!r$t @nd foremo$t, ! feel !t @$ @ gre@t pr!v!lege !n expre$$!ng my deepe$t @nd mo$t $!
ncere gr@t!tude to my $uperv!$or Prof N.K Rout, for h!$ excellent gu!d@nce throughout our
$em!n@r work. H!$ k!ndne$$, ded!c@t!on, h@rd work @nd @ttent!on to det@!l h@ve been
@ gre@t !n$p!r@t!on to me. My he@rtfelt th@nk$ to you $!r for the unl!m!ted $upport @nd
p@t!ence $hown to me. ! would p@rt!cul@rly l!ke to th@nk h!m for @ll h!$ help !n p@t!
ently @nd c@refully correct!ng @ll the follow!ng report det@!l$.

! @m @l$o very th@nkful to our De@n Profe$$or Dr. @run Kum@r R@y @nd @$$oc!
@te De@n Profe$$or @ml@n Dutt@, for the!r $upport @nd $ugge$t!on dur!ng our cour$e
of the $em!n@r !n the f!n@l ye@r of our undergr@du@te cour$e.

@@$th@ $!ngh

2
 @B$TR@CT
M!crob!ovore$ @re noth!ng but @rt!f!c!@l wh!te blood cell$. Th!$ n@norobot $c@l!ng
$tudy for @rt!f!c!@l mech@n!c@l ph@gocyte$ of m!cro$cop!c $!ze, c@lled “m!crob!vore$,”
who$e pr!m@ry funct!on !$ to de$troy m!crob!olog!c@l p@thogen$ found !n the hum@n
blood$tre@m u$!ng @ d!ge$t @nd d!$ch@rge protocol. The m!crob!vore !$ @n obl@te
$phero!d@l n@nomed!c@l dev!ce me@$ur!ng 3.4 m!cron$ !n d!@meter @long !t$ m@jor
@x!$ @nd 2.0 m!cron$ !n d!@meter @long !t$ m!nor @x!$, con$!$t!ng of 610 b!ll!on prec!
$ely @rr@nged $tructur@l @tom$ !n @ gro$$ geometr!c volume of 12.1 m!cron3 . The dev!
ce m@y con$ume up to 200 pW of cont!nuou$ power wh!le completely d!ge$t!ng tr@pped m!
crobe$ @t @ m@x!mum throughput of 2 m!cron3 of org@n!c m@ter!@l per 30-$econd cycle.
M!crob!vore$ @re up to ~1000 t!me$ f@$ter-@ct!ng th@n e!ther n@tur@l or @nt!b!ot!c-@$
$!$ted b!olog!c@l ph@gocyt!c defen$e$, @nd @re ~80 t!me$ more eff!c!ent @$ ph@gocyt!c
@gent$ th@n m@croph@ge$, !n term$ of volume/$ec d!ge$ted per un!t volume of ph@gocyt!
c @gent. !t !$ @n !de@l n@notechnology-b@$ed drug del!very $y$tem wh!ch !$—$elf-
powered, computer-controlled med!c@l n@norobot $y$tem c@p@ble of d!g!t@lly prec!$e
tr@n$port, t!m!ng, @nd t@rgeted del!very of ph@rm@ceut!c@l @gent$ to $pec!f!c cellul@r
@nd !ntr@cellul@r de$t!n@t!on$ w!th!n the hum@n body. M!crob!vore$ w!ll h@ve m@ny
@ppl!c@t!on$ !n n@nomed!c!ne $uch @$ !n!t!@t!on of @popto$!$ !n c@ncer cell$ @nd d!
rect control of cell $!gn@l!ng proce$$.

CONTENT$

T!TLE P@GE NO.

3
 @cknowledgement 2
@b$tr@ct 3 1.!
ntroduct!on 6
1.1 !ntroduct!on to m!crob!vore$ 6
1.2 Def!n!t!on of m!crob!vore$ 6
2. H!$tory @nd commerc!@l!$@t!on of m!crob!vore$ 9
2.1 H!$tory of m!crob!vore$ 9
2.2 Commerc!@l explor@t!on of m!crob!vore$ 10
3. M!crob!@l !nfect!on$ 11
3.1 $ep$!$ @nd $ept!c!m!@ 11
3.2 B@cterem!@ 11
3.3 V!rem!@ 12
3.4 Fungem!@ 13
3.5 P@r@$!tem!@ @nd r!ckett$em!@ 13
4. Purpo$e of m!crob!vore$ 15
4.1 Need for m!crob!vore$ 15
4.2 Work!ng of m!crob!vore$ 16
4.3 Comp@r!$on w!th n@tur@l ph@gocyte$ 17
4.4 Expl@n@ry de$cr!pt!on 18
5. $en$or$ of m!crob!vore$ 22
5.1 The v@r!ou$ $en$or$ 22
5.2 Tre@tment w!th m!crob!vore$ 23
6. @ppl!c@t!on$ 25
6.1 @ppl!c@t!on$ of m!crob!vore$ 25
6.2 U$e$ !n med!c!ne 25
6.2.1 B!ommet!c$ 26
6.2.2 P@tent$ @nd other @ppl!c@t!on$ 26
6.3 Ph@gocyt!c @ct!v!ty of m!crob!vore$ 28

4
 6.4 M!crob!vore ph@rmocok!net!c 30
7. Technology u$ed 32 7.1
V@r!ou$ comput@t!on@l t@$k$ 32
7.2 Common funct!on$ requ!r!ng onbo@rd comput@t!on$ 33
7.3 N@norobot control protocol$ 37
8. @dv@nt@ge$ @nd d!$@dv@nt@ge$ of m!crob!vore$ 41
8.1 @dv@nt@ge$ of m!crob!vore$ 41
8.2 D!$@dv@nt@ge$ of m!crob!vore$ 41
9. Future $cope of m!crob!vore$ 42
Conclu$!on 43
Reference$ 45

CH@PTER 1
!NTRODUCT!ON
1.1 !NTRODUCT!ON TO M!CROB!VORE$

!t !$ !de@l veh!cle to be t@rget@ble to @ll !nd!v!du@l cell$ w!th!n @ g!ven t!$$ue or

5
org@n th@t po$$e$$ed @ p@rt!cul@r ch@r@cter!$t!c (e.g., @ll c@ncer cell$, or @ll
b@cter!@l cell$ of @ def!n!te $pec!e$, etc.). Th!$ !de@l veh!cle would be b!ocomp@t!ble
@nd v!rtu@lly 100% rel!@ble, w!th @ll drug molecule$ be!ng del!vered only to the de$!red
t@rget cell$ @nd none be!ng del!vered el$ewhere $o th@t unw@nted $!de effect$ @re el!m!
n@ted.
The !de@l veh!cle would rem@!n under the cont!nuou$ control of the $uperv!$!ng phy$!c!
@n, !nclud!ng po$t-@dm!n!$tr@t!on. Even @fter the veh!cle$ h@d been !njected !nto the
body, the doctor would $t!ll be @ble to @ct!v@te or !n@ct!v@te them remotely, or @lter
the!r mode of @ct!on or oper@t!on@l p@r@meter$. Once tre@tment w@$ completed, @ll
of the veh!cle$ could be removed !nt@ct from the body, le@v!ng no tr@ce of the!r pre$ence.
Let’$ c@ll th!$ hypothet!c@l !de@l drug del!very veh!cle @ “m!crob!vore.” M!crob!vore$
@re be!ng $elf-powered, computer-controlled n@norobot!c $y$tem$ c@p@ble of d!g!t@lly
prec!$e tr@n$port, t!m!ng, @nd t@rgeted del!very of ph@rm@ceut!c@l @gent$ to $pec!f!c
cellul@r @nd !ntr@cellul@r de$t!n@t!on$ w!th!n the hum@n body. Drug molecule$ could
be purpo$ely del!vered to one cell, but not to @n @dj@cent cell, !n the $@me t!$$ue. To
fully @pprec!@te the $cope of th!$ future development !t !$ helpful to br!efly rev!ew $ome
of the b@ckground @nd recent h!$tory of med!c@l n@norobot!c$.
N@nomed!c!ne offer$ the pro$pect of powerful new tool$ for the tre@tment of hum@n d!
$e@$e$ @nd the @ugment@t!on of hum@n b!olog!c@l $y$tem$. D!@mond-b@$ed med!
c@l n@norobot!c$ m@y offer $ub$t@!n@l !mprovement$ !n c@p@b!l!t!e$ over n@tur@l
b!olog!c@l $y$tem$, exceed!ng even the !mprovement$ po$$!ble v!@ t!$$ue eng!neer!ng
@nd b!otechnology.
Th!$ !$ @ $c@l!ng $tudy for @rt!f!c!@l mech@n!c@l ph@gocyte$ of m!cro$cop!c $!ze,
c@lled "m!crob!vore$." M!crob!vore$ con$t!tute @ l@rge cl@$$ of med!c@l n@norobot$ !
ntended to be deployed !n hum@n p@t!ent$ for @ w!de v@r!ety of @nt!m!crob!@l
ther@peut!c purpo$e$, @$, for ex@mple, @ f!r$t-l!ne re$pon$e to $ept!cem!@. The
@n@ly$!$ here focu$e$ on @ rel@t!vely $!mple dev!ce: @n !ntr@venou$ (!.V.) m!crob!
vore who$e pr!m@ry funct!on !$ to de$troy m!crob!olog!c@l p@thogen$ found !n the
hum@n blood$tre@m, u$!ng the "d!ge$t @nd d!$ch@rge protocol The n@nodev!ce
con$ume$ 100-200 pW of cont!nuou$ power wh!le !n oper@t!on @nd c@n completely d!
ge$t tr@pped m!crobe$ @t @ m@x!mum throughput of 2 m!cron per 30-$econd cycle,
l@rge enough to !ntern@l!ze @ $!ngle m!crobe from v!rtu@lly @ny m@jor b@cterem!c
$pec!e$ !n @ $!ngle gulp.
1.2 DEF!N!T!ON OF M!CROB!VORE$ :

@ n@norobot!c dev!ce th@t could $@fely prov!de qu!ck @nd complete er@d!c@t!on of
bloodborne p@thogen$ u$!ng rel@t!vely low do$e$ of dev!ce$ would be @ welcome @dd!t!
on to the phy$!c!@n’$ ther@peut!c @rm@ment@r!um. $uch @ m@ch!ne !$ the m!crob!
vore, @n @rt!f!c!@l mech@n!c@l ph@gocyte.
The m!crob!vore !$ @n obl@te $phero!d@l n@nomed!c@l dev!ce con$!$t!ng of 610 b!ll!on
prec!$ely @rr@nged $tructur@l @tom$ plu$ @nother ~150 b!ll!on mo$tly g@$ or w@ter
molecule$ when fully lo@ded. The n@norobot me@$ure$ 3.4 m!cron$ !n d!@meter @long !
6
t$ m@jor @x!$ @nd 2.0 m!cron$ !n d!@meter @long !t$ m!nor @x!$, thu$ en$ur!ng re@dy
p@$$@ge through even the n@rrowe$t of hum@n c@p!ll@r!e$ wh!ch @re ~4 m!cron$ !n
d!@meter.
!t$ gro$$ geometr!c volume of 12.1056 m!cron !nclude$ two norm@lly empty !ntern@l
m@ter!@l$ proce$$!ng ch@mber$ tot@l!ng 4 m!cron !n d!$pl@ced volume. The n@nodev!
ce con$ume$ 100-200 pW of cont!nuou$ power wh!le !n oper@t!on @nd c@n completely d!
ge$t tr@pped m!crobe$ @t @ m@x!mum throughput of 2 m!cron per 30-$econd cycle,
l@rge enough to !ntern@l!ze @ $!ngle m!crobe from v!rtu@lly @ny m@jor b@cterem!c
$pec!e$ !n @ $!ngle gulp. @$ !n prev!ou$ de$!gn$, to help en$ure h!gh rel!@b!l!ty the m!
crob!vore h@$ tenfold redund@ncy !n @ll m@jor component$, exclud!ng only the l@rge$t
p@$$!ve $tructur@l element$. The m!crob!vore h@$ @ dry m@$$ of 12.2 p!cogr@m$.
The m!crob!vore, @n @rt!f!c!@l wh!te cell, flo@t$ @long !n the blood$tre@m pr!or to
encounter!ng @ p@thogen. Th!$ !m@ge, the b!nd!ng $!te @rr@y$ @ppe@r @$ mult!
colored c!rcul@r d@pple$ on the blue $@pph!re-colored $urf@ce.

F!G 1.1 RED BLOOD CELL$

Dur!ng e@ch cycle of n@norobot oper@t!on, @ t@rget b@cter!um become$ bound to the
$urf@ce of the bloodborne m!crob!vore l!ke @ fly on flyp@per, v!@ $pec!e$- $pec!f!c
rever$!ble b!nd!ng $!te$. Tele$cop!ng robot!c gr@pple$ emerge from $!lo$ !n the dev!ce
$urf@ce, e$t@bl!$h $ecure @nchor@ge to the m!crobe’$ pl@$m@ membr@ne, then
tr@n$port the p@thogen to the !nge$t!on port @t the front of the dev!ce where the p@thogen
cell !$ !ntern@l!zed !nto @ 2 m!cron 3 morcell@t!on ch@mber. @fter $uff!c!ent mech@n!
c@l m!nc!ng, the chopped-up rem@!n$ of the cell @re p!$toned !nto @ $ep@r@te 2 m!
cron$ d!ge$t!on ch@mber where @ preprogr@mmed $equence of 40 eng!neered enzyme$
@re $ucce$$!vely !njected @nd extr@cted $!x t!me$, progre$$!vely reduc!ng the m@$h to
@m!no @c!d$, mononucleot!de$, $!mple f@tty @c!d$ @nd $ug@r d!ge$t!on ch@mber
where @ preprogr@mmed $equence of 40 eng!neered enzyme$ @re $ucce$$!vely !njected
@nd extr@cted $!x t!me$, progre$$!vely reduc!ng the m@$h to @m!no @c!d$,
mononucleot!de$, $!mple f@tty @c!d$ @nd $ug@r$.
The$e b@$!c molecule$ @re then h@rmle$$ly d!$ch@rged b@ck !nto the blood$tre@m
through @n exh@u$t port @t the re@r of the dev!ce, complet!ng the 30-$econd d!ge$t!on
7
cycle. No m@tter th@t @ b@cter!um h@$ @cqu!red mult!ple drug re$!$t@nce to @nt!b!
ot!c$ or to @ny other tr@d!t!on@l tre@tment – the m!crob!vore w!ll e@t !t @nyw@y,
@ch!ev!ng complete cle@r@nce of even the mo$t $evere bloodborne !nfect!on$ !n m!nute$
to hour$ r@ther th@n t@k!ng week$ to month$ u$!ng pre$ent-d@y @nt!b!ot!c$, u$!ng only
@ few cc’$ of n@norobot$. Hence m!crob!vore$, e@ch 2-3 m!cron$ !n $!ze, would be up
to~1000 t!me$ f@$ter-@ct!ng th@n e!ther un@!ded n@tur@l or @nt!b!ot!c-@$$!$ted b!
olog!c@l ph@gocyt!c defen$e$. Rel@ted n@norobot$ could be progr@mmed to recogn!ze
@nd d!$$olve c@ncer cell$, or to cle@r c!rcul@tory ob$truct!on$ !n @ t!me on the order of
m!nute$, thu$ qu!ckly re$cu!ng the $troke p@t!ent from !$chem!c d@m@ge

8
 CH@PTER 2
H!$TORY @ND COMMERC!@L!$@T!ON OF M!CROB!VORE$
2.1 H!$TORY OF M!CROVORE$
The m!crob!vore concept w@$ !nvented by Robert @. Fre!t@$ Jr., who h@$ outl!ned the!r
de$!gn !n gre@t det@!l. @t pre$ent (2010) we l@ck the "@tom-by-@tom" molecul@r
m@nuf@ctur!ng technology requ!red to con$truct $uch @ dev!ce. $ome futur!$t$ expect
the dre@m of molecul@r n@notechnology (f!r$t conc!eved by Dr. Er!c Drexler) to become
@ re@l!ty $omet!me next dec@de, (2020-2030) en@bl!ng @ m@$$!ve le@p forw@rd n
our con$truct!on c@p@b!l!t!e$. 
Numerou$ p@tholog!e$ ex!$t th@t @re c@u$ed by the pre$ence of fore!gn org@n!$m$ !n
the blood$tre@m. !nfect!on by fore!gn blood-borne org@n!$m$ !$ e$pec!@lly d@ngerou$
!n !nd!v!du@l$ w!th comprom!$ed !mmune $y$tem$ ($uch @$ tho$e $uffer!ng from @!
D$.) Current method$ to control $uch org@n!$m$ @re l@rgely !neffectu@l, or merely
tempor@r!ly @rre$t the!r growth r@ther th@n w!p!ng them out ent!rely. Mo$t phy$!c!
@n$ would welcome the @dd!t!on of $ynthe!tc n@norobot$ c@p@ble of $elect!vely
@nn!h!l@t!ng $uch org@n!$m$. 
The m!crob!vore de$!gn c@ll$ for @ 3.4 m!cron (m!ll!onth$ of @ meter) long, by 2 m!
cron w!de obl@te $phero!d $h@ped dev!ce, con$!$t!ng of 610 b!ll!on $tructur@l @tom$,
@nd f!lled w!th roughly 150 b!ll!on g@$/w@ter molecule$. The ent!re n@nobot h@$ @
gro$$ geometr!c volume of ju$t over 12.1 cub!c m!cron$ (!nclud!ng two norm@lly empty !
ntern@l m@ter!@l$ proce$$!ng b@y$ tot@ll!ng 4 cub!c m!cron$ of d!$pl@ced volume.) !
t$ $!ze en$ure$ unob$tructed p@$$@ge through even the n@rrowe$t of hum@n c@p!
ll@r!e$, wh!ch @re @pprox!m@tely 4 m!cron$ !n d!@meter. @ $!ngle m!crob!vore w!ll
con$ume 100-200 p!cow@tt$ of cont!nuou$ power wh!le !n oper@t!on, @nd w!ll d!ge$t
@nd el!m!n@te p@thogen!c m!crobe$ @t @ m@x!mum throughput of 2 cub!c m!cron$
per 30 $econd cycle - enough room to !ntern@l!ze v!rtu@lly @ny $pec!e$ of b@cter!@ !n
@ $!ngle gulp. The de$!gn !nclude$ 10-fold renund@ncy on mo$t mech@n!$m$, except!
ng the l@rge$t $tructur@l element$, to en$ure h!gh rel!@b!l!ty. 
@$ w!th n@tur@l ph@gocyte$, m!crob!vore$ would devour, d!ge$t, @nd d!$ch@rge @ny
v!ru$e$, b@cter!@ or fung! unlucky enough to be detected. The m!crob!vore would u$e
$pec!e$-$pec!f!c rever$!ble b!nd!ng $!te$ to f!rmly @tt@ch !t$elf to the m!crobe, wh!ch
would then be d!rected to the !nge$t!on port by tele$cop!ng robot!c gr@pple$ !n @ $!m!
l@r f@$h!on to the w@y @ $qu!d u$e$ !t$ tent@cle$ to c@tch @nd hold !t$ prey wh!le
con$um!ng !t. From the !nge$t!on ch@mber, the t@rgetted m!crobe would be blended by
mech@n!c@l bl@de$ !n @ morcell@t!on ch@mber, then p@$$ed to @ d!ge$t!on
ch@mber where the proce$$ed rem@!n$ of the !nv@der would be chem!c@lly @n@lyzed
before be!ng further broken down by @ $pec!f!c@lly $elected $equence of 40 eng!neered
enzyme$, !nto b!olog!c@lly neutr@l effluent (mononucleot!de$, @m!no @c!d$, free f@tty
@c!d$, $!mple $ug@r$ @nd glycerol.) wh!ch would be rele@$ed h@rmle$$ly b@ck !nto
the blood$tre@m through @n exh@u$t port on the b@ck of the dev!ce, where !t could be
u$ed by the body'$ molecul@r m@ch!nery (cell$) for !t$ nutr!t!on@l content. 
Gett!ng m!crob!vore$ !nto the body would be @ m@tter of $!mply !ntroduc!ng them !
ntr@venou$ly. Prel!m!n@ry e$t!m@te$ $ugge$t m!crob!vore$ would be @round 80 t!me$
more eff!c!ent, @nd @bout 1,000 t!me$ f@$ter @ct!ng th@n our n@tur@l wh!te blood
cell$. Once the!r m!$$!on !$ complete they could be progr@mmed to ex!t the blood$tre@m
v!@ the !nte$t!ne$, !f de$!red. Cl!n!c@l u$e of m!crob!vore$, @nd the m@ny other $pec!
9
e$ of n@nobot$ thu$ f@r !m@g!ned, could revolut!on!ze the f!eld of med!c!ne. M@$$
f@br!c@t!on @nd ther@put!c u$e of $uch dev!ce$ (th@nk$ to molecul@r n@notech) over
the com!ng dec@de$ w!ll le@d to cure$ for m@ny d!$e@$e$, b@rr!ng @ny unfor$een !
n$urmount@ble techn!c@l ch@llenge$, for m@ny people @l!ve tod@y.

2.2 COMMERC!@L EXPLOR@T!ON

Mo$t of the comp@n!e$ !nvolved !n the development @nd commerc!@l!$@t!on of
n@nom@ter!@l$ !n b!olog!c@l @nd med!c@l$ @ppl!c@t!on$ @re develop!ng
ph@rm@ceut!c@l @ppl!c@t!on$, m@!nly for drug del!very.Mo$t of the e$t@bl!$hed
ph@rm@ceut!c@l comp@n!e$ h@ve !ntern@l re$e@rch progr@m$ on drug del!very
th@t !nve$t!g@te formul@t!on$ or d!$per$!on$ cont@!n!ng n@no$c@le
component$.For,ex@mple,collo!d@l $!lver u$ed !n @nt!m!crob!@l formul@t!on$ @nd
dre$$!ng$,@$ the $!lver !on$ block the cellul@r re$p!or@t!on of m!crobe$,$mother!ng
h@rmful cell$ @nd k!ll!ng them.The h!gh re@ct!v!ty of t!t@n!@ n@nop@rt!clre$, e!ther
on the!r own or when !llum!n@ted w!th UV l!ght,!$ @ppl!ed for b@cter!@l purpo$e$ !n f!
lter$.The enh@nced $urf@ce c@t@lyt!c propert!e$ of n@no-cer@m!c$ or tho$e of noble
met@l$ l!ke pl@t!num c@n be put to u$e de$troy!ng d@ngerou$ tox!n$ @nd other
h@z@rdou$ org@n!c m@ter!@l$ e!ther !n$!de or out$!de the body.
$ever@l comp@n!e$ e!ther explo!t qu@ntum $!ze effect$ !n $em!conductor
n@nocry$t@l$ for t@gg!ng b!komolecule$ or u$e b!o-conjug@ted gold n@nop@rt!cle$
for l@bel!ng for v@r!ou$ cellul@r cellul@r p@rt$.@ number of comp@n!e$ @re @pply!
ng n@nocer@m!c m@ter!@l$ for t!$$ue eng!neer!ng @nd orthoped!c$.
!n b!o$c!ence$,n@nop@rt!cle$ @re repl@c!ng org@n!c dye$ !n @ppl!c@t!on$ th@t
requ!tre h!gh photo-$t@b!l!ty @$ well @$ h!gh mult!plex!ng c@p@b!l!t!e$.For
ex@mpke,org@n!c dye$ @re convent!on@ly u$ed for t@gg!ng cell$,prote!n$ @nd DN@
for !dent!f!c@t!on !n v@r!ou$ re$e@rch $tud!e$.Yet,$uch dye$ @re gr@du@lly be!ng
repl@ced by n@nop@rt!cle$.!n @dd!t!onto be!ng br!ghter @nd more $t@ble ,n@nop@rt!
cle$ en@ble t@gg!ng of mult!ple b!olog!c@l $ub$t@nce$ @t the $@me t!me or !n the
$@me @re@ through the u$e of d!fferent p@rt!cle $!ze$ @nd $h@pe$.The p@rt!cle$
ret@!n the!r !nd!v!du@l!$ed t@g ch@r@cter!$t!c$ where@$ org@n!c dye$ c@n blend
together.N@nop@rt!cle$ c@n therefore m@ke !t po$$!ble to conduct mult!ple exper!
ment$ $!mult@neou$ly !n @ g!ven @re@, w!thout u$!ng the re@gent$ @nd $pec!@l!$ed
l!ght-f!lter!ng equ!pment often needed for org@n!c dye$.

10
 CH@PTER 3
M!CROB!@L !NFECT!ON$

3.1 $EP$!$ @ND $EPT!C!M!@

$ep$!$ !$ @ p@tholog!c@l $t@te, u$u@lly febr!le, re$ult!ng from the pre$ence of m!
croorg@n!$m$ or the!r po!$onou$ product$ !n the blood$tre@m . M!crob!@l !nfect!on
m@y m@n!fe$t @$ cellul!t!$ (loc@l d!$$em!n@t!on of !nfect!on), lymph@ng!t!$ or
lymph@den!t!$ (d!$per$!on @long lymph@t!c ch@nnel$) or $ept!cem!@ (w!de$pre@d
d!$$em!n@t!on v!@ the blood$tre@m). $ept!cem!@, @l$o known @$ blood po!$on!ng,
!$ the pre$ence of p@thogen!c m!croorg@n!$m$ !n the blood. !f @llowed to progre$$,
the$e m!croorg@n!$m$ m@y mult!ply @nd c@u$e @n overwhelm!ng !nfect!on.
$ymptom$ !nclude ch!ll$ @nd fever, petech!@e ($m@ll purpl!$h $k!n $pot$), purpur!c
pu$tule$ @nd @b$ce$$e$. @cute $ept!cem!@, wh!ch !nclude$ t@chyc@rd!@,
t@chypne@, @nd @ltered ment@l funct!on, m@y comb!ne w!th hypoten$!on @nd !
n@dequ@te org@n perfu$!on @$ $ept!c $hock -- the re$ult!ng decre@$ed myoc@rd!@l
contr@ct!l!ty @nd c!rcul@tory f@!lure c@n le@d to w!de$pre@d t!$$ue !njury @nd
eventu@lly mult!ple org@n f@!lure @nd de@th , often !n @$ few @$ 1-3 d@y$. R!$k !
$ e$pec!@lly h!gh for !mmune-comprom!$ed !nd!v!du@l$ -- !n one @n!m@l $tudy, the
LD50* for m!ce rendered leukopen!c (def!ned @$ <10% norm@l leukocr!t) w@$ le$$
th@n 20 b@cter!@ of the $pec!e$ P$eudomon@$ @erug!no$@. @$plen!c p@t!ent$ @re
p@rt!cul@rly $u$cept!ble to r@p!dly progre$$!ve $ep$!$ from enc@p$ul@ted m!
croorg@n!$m$ $uch @$ $treptococc@l pneumon!@, hemoph!lu$ !nfluenz@ @nd men!
ngococcu$, @nd w!ll d!e !f the !nfect!on !$ not recogn!zed r@p!dly @nd tre@ted @ggre$
$!vely.

F!G 1.2 $EPT!CEM!@

$ept!cem!@ m@y be c@u$ed by $ever@l d!fferent cl@$$e$ of p@thogen!c
org@n!$m$, mo$t commonly !dent!f!ed @$ b@cter!@ (b@cterem!@), v!ru$e$
(v!rem!@),fung! (fungem!@), p@r@$!te$ (p@r@$!tem!@) @nd r!ckett$!@e (r!
ckett$em!@).

3.2 B@CTEREM!@

11
The he@lthy hum@n blood$tre@m !$ gener@lly con$!dered @ $ter!le env!ronment.
@lthough b@cter!@l nutr!ent$ @re plent!ful !n blood, m@jor @nt!m!crob!@l defen$e$
!nclude the c!rcul@t!ng neutroph!l$ @nd monocyte$ c@p@ble of ph@gocyto$!$ @nd
the $upport!ng component$ of humor@l !mmun!ty !nclud!ng complement @nd !
mmunoglobul!n$.

$t!ll, !t !$ not unu$u@l to f!nd @ few b@cter!@ !n blood. Norm@l @ct!v!t!e$ l!ke chew!
ng, bru$h!ng or flo$$!ng teeth c@u$e$ movement of teeth !n the!r $ocket$, !nfu$!ng @
bur$t of commen$@l or@l m!crobe$ !nto the blood$tre@m. B@cter!@ c@n enter the
blood v!@ @n !njury to the $k!n, the l!n!ng of the mouth or gum$, or from g!ng!v!t!$ or
other m!nor !nfect!on$ !n the $k!n @nd el$ewhere. B@cterem!@$ from @ focu$ of !
nfect!on @re u$u@lly !nterm!ttent, wh!le tho$e from v@$cul@r $y$tem !nfect!on tend to
be cont!nuou$, $uch @$ endoc@rd!t!$ or embol!$m from he@rt v@lve veget@t!on$ !n
$ub@cute b@cter!@l endoc@rd!t!$ ($BE), $omet!me$ le@d!ng to !nfect!ou$ mycot!c
(e.g., $t@phylococcu$ @ureu$) @neury$m$.

B@cter!@ c@n @l$o enter the blood dur!ng $urg!c@l, dent@l, or other med!c@l
procedure$
$uch @$ the !n$ert!on of !.V. l!ne$ (prov!d!ng flu!d$, nutr!t!on or med!c@t!on$),
cy$to$copy (@ v!ew!ng tube !n$erted to ex@m!ne the bl@dder), colono$copy (@ v!ew!
ng tube !n$erted to v!ew the colon), or he@rt v@lve repl@cement w!th @ pro$thet!c
(th@nkfully now r@re, due to he@vy preoper@t!ve do$!ng w!th cef@zol!n). $uch
b@cter!@ @re norm@lly removed by c!rcul@t!ng leukocyte$ (@long w!th the f!xed ret!
culoendothel!@l cell$ !n the $pleen, l!ver, @nd lung$), but @ few $pec!e$ of b@cter!@
@re unu$u@lly v!rulent @nd c@n overwhelm the n@tur@l defen$e$. The CDC e$t!
m@te$ th@t ~25,000 U.$. p@t!ent$ d!e e@ch ye@r from b@cter!@l $ep$!$. Worldw!de,
there @re ~1.5 m!ll!on c@$e$ of $ep$!$ @nd ~0.5 m!ll!on de@th$ from $ep$!$
@nnu@lly. @nt!b!ot!c$ c@n f!ght $ep$!$, pre$$or$ c@n rel!eve hypoten$!on from $ep$!
$, volume repl@cement @nd !.V. @lbum!n or HE$P@N (het@$t@rch) c@n off$et
hypovolem!@, but unt!l recently there h@ve been no ph@rm@colog!c@l @gent$
@pproved to f!ght the compl!c@t!on$ of co@gul@t!on @nd !nfl@mm@t!on due to
b@cter!@l endotox!n(wh!ch c@n $t!ll le@d to @ mort@l!ty r@te of 30%-50% @lthough
@nt!endotox!n pept!de$ @nd @nt!-LP$ monoclon@l @nt!bod!e$@re be!ng !nve$t!
g@ted for th!$ purpo$e.

3.3 V!rem!@

V!rem!@ !$ the pre$ence of v!ru$ p@rt!cle$ !n the blood$tre@m, u$u@lly @ tr@n$!ent

cond!t!on . V!ru$e$ @re @cellul@r b!o@ct!ve p@r@$!te$ th@t @tt@ck v!rtu@lly
every form of cellul@r l!fe. V!ru$e$ h@ve d!@meter$ r@ng!ng from 16-300 nm -- for
ex@mple, pol!omyel!t!$ ~18 nm, yellow fever ~25 nm, @denov!ru$ (common cold) ~70
nm, !nfluenz@ (flu) ~100 nm, herpe$ $!mplex @nd r@b!e$ ~125 nm, @nd p$!tt@co$!$
~275 nm. The!r $h@pe !$ e!ther p$eudo$pher!c@l w!th !co$@hedr@l $ymmetry, @$ !n
the pol!omyel!t!$ v!ru$, or rodl!ke, @$ !n the tob@cco mo$@!c v!ru$ (TMV). @ v!ru$
$urrounded only by prote!n co@t (c@p$!d) !$ @ n@ked v!ru$; $ome v!ru$e$ (e.g., H!V,
H$V, pox), c@lled enveloped v!ru$e$, @cqu!re @ l!p!d membr@ne envelope from the!r
ho$t cell upon rele@$e.
12
!n c@$e$ of blood pl@$m@ v!rem!@, v!r!on p@rt!cle count$ r@nge from 1/ml to 0.35
×106/ml for H!V !n hum@n$, w!th @ me@n of 25/ml for @$ymptom@t!c p@t!ent$; v!
r@l lo@d$ for $!m!@n !mmunodef!c!ency v!ru$ ($!V) !n monkey$ m@y be much h!
gher, 2-200 ×106/ml of blood. Hep@t!t!$ C (HCV) !nfect!ou$ v!r@l lo@d$ (@t ~10-18
gm/v!r!on) @re con$!dered low @t 0.2-1 × 106/ml, med!um @t 1-5 ×106/ml, h!gh @t 5-
25 ×106/ml, @nd very h!gh @t >25 ×106/ml. Hep@t!t!$ G (HGV) v!r@l lo@d$ !n
$ymptom@t!c p@t!ent$ @re 0.16-
5.1 ×106/ml. TT v!ru$ (TTV) lo@d$ !n H!V p@t!ent$ m@y exceed >0.35 ×106/ml. Thu$
the typ!c@l blood p@rt!cle burden$ !n v!rem!@ @re much the $@me @$ !n b@cterem!
@, roughly 0.1-100 ×106/ml. V!r@l !nfect!on$ c@n be very d!ff!cult to er@d!c@te
ph@rm@ceut!c@lly, @$ mo$t tre@tment$ @re v!ru$t@t!c, not v!ruc!d@l. For
ex@mple, @cute tre@tment of herpe$v!ru$ requ!re$ 2 gr@m$/d@y of @cyclov!r, w!th
chron!c $uppre$$!ve ther@py for recurrent d!$e@$e requ!r!ng 0.8 gr@m$/d@y for up to
12 month$.

3.4 Fungem!@
!n $everely !mmunocomprom!$ed p@t!ent$, fung! m@y g@!n @cce$$ to the
blood$tre@m, produc!ng fungem!@. Fung@l cell$ !n per!pher@l blood @re typ!c@lly
ovo!d to elong@ted, from 3 × 3 m!cron$ up to 7 ×10 m!cron$ !n $!ze, @nd occur $!ngly,
budd!ng, or !n $hort ch@!n$ @nd clu$ter$. C@nd!d@l fungem!@ !$ mo$t common;
C@nd!d@ @lb!c@n$ blood count$ !n hum@n p@t!ent$ @re con$!dered "ultr@low" @t
< 1 CFU/ml @nd "low" @t 1-3 CFU/ml !n neon@te$, but "h!gh" @t > 5 CFU/ml !n
@dult p@t!ent$; !n one te$t $er!e$, fungem!c p@t!ent$ $howed 5.5 CFU/ml !n venou$
blood @nd 9.1 CFU/ml !n @rter!@l blood, $ugge$t!ng th@t per!pher@l t!$$ue$ m@y
cle@r ~40% of ye@$t$. R@t$ !njected w!th ~100 ×106 CFU/ml of C. @lb!c@n$ @ll d!
ed !n < ~6 hour$ from nonendotoxem!c (!.e., non-LP$ rel@ted) $hock.

P@t!ent$ w!th c@theter-rel@ted fungem!@ due to fungu$ count$ of M@l@$$ez!@

furfur @t 50- 1000 CFU/ml requ!red @nt!b!ot!c tre@tment, @nd c@theter-rel@ted
Rhodotorul@ (red ye@$t) !nfected p@t!ent$ w!th colony count$ !n the 100-1000 CFU/ml
r@nge requ!red @nt!fung@l ther@py. Hum@n blood$tre@m fung@l !nfect!on$ thu$
@ppe@r to r@nge from 1-1000 CFU/ml. D!$$em!n@ted ($y$tem!c) c@nd!d!@$!$ !$
effect!vely m@n@ged w!th 0.2 gm/d@y of flucon@zole for @t le@$t 4 week$. Cocc!d!
o!de$ !mm!t!$ fung@l !nfect!on !$ tre@ted w!th ~0.02 gm/d@y (~200 ml/d@y !.V. dr!p
$olut!on v!@ Omm@y@ re$ervo!r !nto the br@!n ventr!cle$) of @mphoter!c!n B for up
to 9-11 month$ (very tox!c, w!th overdo$e le@d!ng to c@rd!o-re$p!r@tory @rre$t; typ!
c@lly do$ed @$ tot@l cumul@t!ve). Re$p!r@tory fung@l h!$topl@$mo$!$ (H!
$topl@$m@ c@pul@tum) m@y be tre@ted w!th or@l do$e$ of !tr@con@zole @t 0.2-
0.5 gm/d@y for @ m!n!mum of 3 month$.

3.5 P@r@$!tem!@ @nd R!ckett$em!@

P@r@$!tem!@ @r!$e$ from p@r@$!te$ th@t h@ve evolved to l!ve !n the blood$tre@m
!nclude the Pl@$mod!um (m@l@r!@) f@m!ly @nd the fl@gell@te protozo@n$
Tryp@no$om@ ($leep!ng $!ckne$$) @nd Le!$hm@n!@ (le!$hm@n!@$!$). Blood
p@r@$!te$ typ!c@lly h@ve @ juven!le form th@t !$ ovo!d or r!ng-$h@ped w!th d!
13
men$!on$ of 1-5 m!cron$, @nd @n @dult tubul@r form me@$ur!ng 1-5 m!cron$ !n w!
dth @nd 10-30 m!cron$ !n length. !n Tryp@no$om@ bruce!, the number of
tryp@no$ome$ !n blood fluctu@te$ !n w@ve$, @nd the org@n!$m$ @re typ!c@lly
undetect@ble for 3 out of 5 d@y$. Trypom@$t!gote$ h@ve @n !.V. LD50 !n m!ce of
~2.5/gm . Tryp@no$om@ bruce! g@mb!en$e !nocul@ted !nto m!ce h@$ @n LD50 of
0.02-0.15 ×106 tryp@no$ome$/gm, w!th growth r@te$ $low!ng @t org@n!$m blood
concentr@t!on$ > 300 ×106 tryp@no$ome$/ml @nd de@th occurr!ng @t @ blood
p@r@$!te lo@d of 2000 ×106 tryp@no$ome$/ml. M@l@r!@ m@y be tre@ted w!th
$ever@l or@l do$e$ of chloroqu!ne pho$ph@te tot@ll!ng 2.5 gm over three d@y$, but
there !$ !ncre@$!ng m!crob!@l re$!$t@nce to chloroqu!ne worldw!de @nd @$ l!ttle @$
1 gm of the med!c!ne c@n be f@t@l !n ch!ldren, w!th tox!c $ymptom$ @ppe@r!ng w!th!
n m!nute$ of overdo$@ge; @ $!ngle 1.25 gm do$e of mefloqu!ne !$ $omet!me$ effect!ve
!n m!ld c@$e$.

R!ckett$!@ @re rod-$h@ped or cocco!d gr@m-neg@t!ve obl!g@te !ntr@cellul@r

p@r@$!te$
~0.25 m!cron$ !n d!@meter th@t !n hum@n$ grow pr!nc!p@lly !n endothel!@l cell$ of
$m@ll blood ve$$el$, produc!ng v@$cul!t!$, cell necro$!$, ve$$el thrombo$!$, $k!n
r@$he$ @nd org@n dy$funct!on$ . The !nfect!on !$ ch@r@cter!zed by repet!t!ve
cycle$ of bloodborne org@n!$m$, or r!ckett$em!@. For ex@mple, !n c@ttle the
number of p@thogen$ !n the blood v@r!e$ between @ low of 100/ml @nd @ pe@k of
1-10 ×106/ml over 6-8 week !nterv@l$; !n e@ch cycle, the blood count $lowly r!$e$
over 10-14 d@y$ @nd then decl!ne$ prec!p!tou$ly . However, mo$t of the$e p@r@$!
te$ @re found !n the red cell$, @nd the org@n!$m'$ @ppe@r@nce !n the blood
pl@$m@ !$ !nc!dent@l to !t$ @ct!v!ty. Pl@$m@ t!ter$ for free R. r!ckett$!! org@n!
$m$ !n the blood of hum@n p@t!ent$ w!th Rocky Mount@!n $potted fever @ver@ged
5-16 p@r@$!te$/ml !n tre@ted p@t!ent$ who $urv!ved, @nd 1000 p@r@$!te$/ml !n
the po$tmortem pl@$m@ of one p@t!ent w!th untre@ted f@t@l fulm!n@nt fever.
@nt!b!ot!c ther@py h@$ reduced the de@th r@te from 20% to @bout 7%, w!th de@th
u$u@lly occurr!ng when tre@tment !$ del@yed.

14
 CH@PTER 4
PURPO$E OF M!CROB!VORE$

4.1 NEED OF M!CROB!VORE

The forego!ng rev!ew $ugge$t$ th@t ex!$t!ng tre@tment$ for m@ny $ept!cem!c @gent$
often requ!re l@rge qu@nt!t!e$ of med!c@t!on$ th@t mu$t be @ppl!ed over long per!od of
t!me; often @ch!eve only !ncomplete er@d!c@t!on, or merely growth @rre$t, of the
p@thogen. @ n@norobot!c dev!ce th@t could $@fely prov!de qu!ck @nd complete er@d!
c@t!on of bloodborne p@thogen$ u$!ng rel@t!vely low do$e$ of dev!ce$ would be @
welcome @dd!t!on to the phy$!c!@n’$ ther@peut!c @rm@ment@r!um.

F!G 4.1 D!GE$T!NG PROTOCOL

De$!gned to tre@t $ept!cem!@ (blood po!$on!ng), m!crob!vore$ would be @ cl@$$ of

med!c@l n@norobot$, m@de of @ d!@mondo!d @rr@ngement of @tom$, th@t t@rget
h@rmful p@thogen$ w!th!n the blood$tre@m. The$e n@norobot$ @re hypothe$!zed to be
1000 t!me$ f@$ter @nd 80 t!me$ more effect!ve th@n the body’$ n@tur@l ph@gocyte$,
15
@nd c@n be @ppl!ed

16
to @ v@r!ety of med!c@l pr@ct!ce$. The m!crob!vore$ would con$!$t of 4 m@!n funct!
on@l group$: @ rever$!ble b!nd!ng $!te, tele$cop!ng gr@pple$, morcell@t!on ch@mber,
@nd d!ge$t!on ch@mber. The rever$!ble b!nd!ng $!te$ u$e l!g@nd receptor$ on the
n@norobot to !dent!fy @ b@cter!@ b@$ed on the content of !t$ cellul@r membr@ne, or
other ch@r@cter!$t!c m@ter!@l$. Once !dent!f!ed, tele$cop!ng gr@pple$ would
m@neuver the b@cter!@ or v!ru$ !nto the morcell@t!on ch@mber where the p@thogen
could be cut !nto d!ge$t!ble p!ece$ for enzym@t!c d!ge$t!on. H@rmle$$ w@$te m@ter!@l$
would be rele@$ed !nto the blood$tre@m @nd the m!crob!vore$ cycled out of the blood
through n@n@phere$!$.

4.2 WORK!NG OF M!CROB!VORE$:

The pr!nc!p@l @ct!v!ty wh!ch dr!ve$ m!crob!vore $c@l!ng @nd de$!gn !$ the proce$$ of d!
ge$t!on of org@n!c $ub$t@nce$, wh!ch @l$o h@$ $ome $!m!l@r!ty to the d!ge$t!on of
food. The m!crob!vore d!ge$t!ve $y$tem h@$ four fund@ment@l component$:
1. @n @rr@y of rever$!ble b!nd!ng $!te$ to !n!t!@lly b!nd
1. Tr@p t@rget m!crobe$; @n @rr@y of tele$cop!ng gr@pple$ to m@n!pul@te the m!
crobe, once tr@pped
2. @ morcell@t!on ch@mber !n wh!ch the m!crobe !$ m!nced !nto $m@ll, e@$!ly d!
ge$ted p!ece$
3. @ d!ge$t!on ch@mber where the $m@ll p!ece$ @re chem!c@lly d!ge$ted

F!G 4.2 P@THOGEN DETECT!ON

Here’$ how the n@norobot work$. Dur!ng e@ch cycle of oper@t!on, the t@rget b@cter!um
!$ bound to the $urf@ce of m!crob!vore l!ke @ fly on flyp@per, v!@ $pec!e$- $pec!f!c
rever$!ble b!nd!ng $!te$. Tele$cop!ng robot!c gr@pple$ emerge from $!lo$ !n the dev!ce
$urf@ce; e$t@bl!$h $ecure @nchor@ge to the m!crobe’$ pl@$m@ membr@ne, then
tr@n$port the p@thogen to the !nge$t!on port @t the front of the dev!ce where the p@thogen
cell !$ !ntern@l!zed !nto 2 m!cron morcell@t!on ch@mber.
@fter $uff!c!ent mech@n!c@l m!nc!ng, the morcell@ted rem@!n$ of the cell @re p!$toned !
nto @ 2 m!cron d!ge$t!on ch@mber where @ preprogr@mmed $equence of 40 eng!neered
enzyme$ @re $ucce$$!vely !njected @nd extr@cted $!x t!me$, progre$$!vely eng!neered
enzyme$ @re $ucce$$!vely !njected @nd extr@cted $!x t!me$, progre$$!vely

17
reduc!ng the morcell@te ult!m@tely to monore$!due @m!no @c!d$, mononucleot!de$,
glycerol, free f@tty @c!d$ @nd $!mple $ug@r$ .
The$e $!mple molecule$ @re then h@rmle$$ly d!$ch@rged b@ck !nto the blood$tre@m
through @n exh@u$t port @t the re@r of the dev!ce, complet!ng the 30-$econd d!ge$t!on
cycle. Th!$ “d!ge$t @nd d!$ch@rge” protocol !$ conceptu@lly $!m!l@r to the !ntern@l!
z@t!on @nd d!ge$t!on proce$$ pr@ct!ced by n@tur@l ph@gocyte$, except th@t the @rt!f!
c!@l proce$$ $hould be much f@$ter @nd cle@ner. For ex@mple, !t !$ well-known th@t
m@croph@ge$ rele@$e b!olog!c@lly @ct!ve compound$ dur!ng b@cter!oph@gy,
where@$ well- de$!gned m!crob!vore$ need only rele@$e b!olog!c@lly !n@ct!ve effluent.
The$e n@norobot$ would con$!$t of 4 m@!n component$: rever$!ble b!nd!ng $!te, tele$cop!
ng gr@pple$, morcell@t!on ch@mber, @nd d!ge$t!on ch@mber. The b@cter!@l
membr@ne of @ll m!crob!@l p@thogen$ cont@!n$ @t le@$t one $pec!e$-$pec!f!c !dent!
fy!ng ch@r@cter!$t!c, whether !t !$ @ c@rbohydr@te ch@!n, $urf@ce prote!n, or @m!no
@c!d. @ rever$!ble b!nd!ng $!te (rever$!b!l!ty be!ng for @ M!crob!vore to @tt@ch to
p@thogen$ more th@n once) on the out$!de of the M!crob!vore @llow$ the n@norobot to !
dent!fy @nd @tt@ch to p@thogen$. Th!$ form of t@rgeted del!very ofn@nomed!c!ne
prevent$ the de$truct!on of helpful b@cter!@, @nd c@n be h!ghly cu$tom!zed, depend!ng
on the number of l!g@nd receptor$ @t the rever$!ble b!nd!ng $!te.
Tele$cop!ng gr@pple$, @tt@ched to the out$!de of the M!crob!vore, would @l$o be equ!
pped w!th b!nd!ng $!te$, @nd help to m@neuver the p@thogen tow@rd$ the !nge$t!on port
@nd !nto the morcell@t!on ch@mber. !n$!de the morcell@t!on ch@mber, the p@thogen !$
morcell@ted (m!nced !nto $m@ll p!ece$), u$!ng d!@mondo!d (re$embl!ng the den$e,
cry$t@ll!ne $tructure of d!@mond or $@pph!re, u$u@lly con$!$t!ng of C-H bond$
$upplemented w!th @tom$ of N,O,$!, @nd $) bl@de$ powered by @ n@nomotor. The
morcell@te would then be tr@n$ferred !nto the d!ge$t!on ch@mber, @ m!xture of pept!
d@$e$ @nd other enzyme$ bre@k down the p@thogen !nto @m!no @c!d$, $!mple
$ug@r$, @nd mononucleot!de$ to be h@rmle$$ly rele@$ed b@ck !nto the
blood$tre@m[1]. @fter tre@tment, M!crob!vore$would be removed though n@n@phere$!$,
@ proce$$ whereby blood !$ cycled through @n @pp@r@tu$ to $ep@r@te n@norobot$
@nd return blood b@ck !nto the body.

4.3 COMP@R!$ON W!TH N@TUR@L PH@GOCYTE$:

N@tur@l ph@gocyt!c cell$ @re 100-1000 t!me$ l@rger !n volume th@n m!crob!vore$ but
m@y con$ume @lmo$t @$ much power dur!ng comp@r@ble @ct!v!t!e$. M!crobe !nge$t!
on t!me$ for n@tur@l profe$$!on@l ph@gocyte$ c@n be qu!te r@p!d, often @ m@tter of
m!nute$, but full d!ge$t!on @nd excret!on of the t@rget p@thogen m@y requ!re hour$. Wh!
le m@croph@ge$ c@n !nge$t up to ~25% of the!r volume per hour, m!crobe$ c@n proce$
$~2000% of the!r volume per hour, thu$ @re ~80 t!me$ more eff!c!ent @$ ph@gocyt!c
@gent$. !n other word$, @ g!ven volume of wh!te cell$ or m@croph@ge$ could d!ge$t
them.
Wh!le m!crob!vore$ c@n fully el!m!n@te $ept!cem!c !nfect!on$ !n m!nute$ to hour$,
n@tur@l ph@gocyt!c defen$e$, even @!ded by @nt!b!ot!c$, c@n often requ!re week$ or
month$ to @ch!eve complete cle@r@nce of t@rget b@cter!@ from the blood$tre@m. Thu$
m!crob!vore$ @ppe@r to be up to ~1000 t!me$ f@$ter-@ct!ng th@n e!ther un@!ded
n@tur@l or @nt!b!ot!c-@$$!$ted ph@gocyt!c defen$e$.

18
 F!G 4.3 N@TUR@L P@THOGEN

Th!$ @ltern@t!ve ver$!on of @rt!f!c!@l wh!te cell$ u$e$ retr@ct@ble tent@cle$, enc!rcl!
ng the m@!n body, to convey the !de@ of p@thogen c@pture, !n pl@ce of the hundred$ of t!
ny tele$cop!ng @rm$ th@t were employed !n Fret!@$’ or!g!n@l techn!c@l m@neuver!ng.
E@ch n@norobot !$ @bout 3 m!cron$ !n $!ze. @ n@tur@l wh!te cell !$ pre$ent !n the
b@ckground to prov!de v!$u@l $c@l!ng. !n the lower !m@ge, the tent@cle$ h@ve been
fully retr@cted.

4.4 EXPL@N@RY DE$CR!PT!ON:

The m!crob!vore, @n @rt!f!c!@l wh!te cell, flo@t$ @long !n the blood$tre@m unt!l !t
encounter$ @ p@thogen. !n th!$ $t!ll-theoret!c@l med!c@l n@norobot $cen@r!o, @ rod
$h@ped b@cter!um h@$ been tr@pped by b!nd!ng $!te d!$k$ on the m!crob!vore hull @nd
then tr@n$ported by t!ny m@n!pul@tor @rm$ to the !nge$t!on port, where upon the m!crobe
d!ge$ted !n$!de the dev!ce. The m!crob!vore !$ @bout 3 m!cron$ !n d!@meter, @nd the b!
nd!ng $!te @rr@y$ @ppe@r @$ mult!colored c!rcul@r d@pple$ on the blue $@pph!re-
colored $urf@ce. !n th!$ !m@ge, the mouth of the n@norobot !$ open. @ few of the
tele$cop!ng gr@pple @rm$ @re extend!ng from the $urf@ce of the dev!ce @nd feed!ng the
rod-$h@ped b@cter!um !nto m!crob!vore’$ mouth.

F!G 4.4 N@NOROBOT$

The de$!gned m!crob!vore$ need only rele@$e b!olog!c@lly !n@ct!ve effluent. The f!r$t
t@$k for the bloodborne m!crob!vore !$ to rel!@bly @cqu!re @ p@thogen to be d!ge$ted. !f
the correct b@cter!um bump$ !nto the n@norobot $urf@ce, rever$!ble $pec!e$- $pec!f!c b!
19
nd!ng $!te$ on the m!crob!vore hull c@n recogn!ze @nd we@kly b!nd to the

20
b@cter!um. @ $et of 9 d!$t!nct @nt!gen!c m@rker$ $hould be $pec!f!c enough [1@c], $!nce
@ll 9 mu$t reg!$ter @ po$!t!ve b!nd!ng event to conf!rm th@t @ t@rgeted m!crobe h@$
been c@ught. There @re 20,000 cop!e$ of the$e 9-m@rker receptor $et$, d!$tr!buted !n 275
d!$k- $h@ped reg!on$ @cro$$ the m!crob!vore $urf@ce. !n$!de e@ch receptor r!ng @re
more rotor$ to @b$orb @mb!ent gluco$e @nd oxygen from the blood$tre@m to prov!de
n@norobot power. @t the center of e@ch 150-nm d!@meter receptor d!$k !$ @ gr@pple $!
lo.

Once @ b@cter!um h@$ been c@ptured by the rever$!ble receptor$, tele$cop!ng robot!c
gr@pple$ r!$e up out of the m!crob!vore $urf@ce @nd @tt@ch to the tr@pped b@cter!um,
e$t@bl!$h!ng $ecure @nchor@ge to the m!crobe’$ pl@$m@ membr@ne. The m!crob!vore
gr@pple @rm$ @re @bout 100 nm long @nd h@ve v@r!ou$ rot@t!ng @nd tele$cop!ng jo!
nt$ th@t @llow them to ch@nge the!r po$!t!on, @ngle, @nd length. @fter r!$!ng out of !t$
$!lo, @ gr@pple @rm c@n execute complex tw!$t!ng mot!on$, @nd @dj@cent gr@pple
@rm$ c@n phy$!c@lly re@ch e@ch other, @llow!ng them to h@nd off bound object$ @$
$m@ll @$ @ v!ru$ p@rt!cle. Gr@pple h@ndoff mot!on$ c@n tr@n$port @ l@rge rod-
$h@ped b@cter!um from !t$ or!g!n@l c@pture $!te forw@rd to the !nge$t!on port @t the
front of the dev!ce.

The c@pt!ve org@n!$m !$ rot@ted !nto the proper or!ent@t!on @$ !t @ppro@che$ the open
m!crob!vore mouth, where the p@thogen cell !$ !ntern@l!zed !nto @ 2 m!cron3 morcell@t!
on ch@mber. There @re two concentr!c cyl!nder$ !n$!de the m!crob!vore. The b@cter!um !$
m!nced !nto n@no$c@le p!ece$ !n the morcell@t!on ch@mber [1@e], the $m@ller !nner
cyl!nder, then the rem@!n$ @re p!$toned !nto @ $ep@r@te 2 m!cron3 d!ge$t!on ch@mber,
@ l@rger outer cyl!nder.

!n @ preprogr@mmed $equence, B40 d!fferent eng!neered d!ge$t!ve enzyme$ @re $ucce$$!

vely !njected @nd extr@cted $!x t!me$ 402 COMPUT@T!ON@L T@$K$ !N MED!C@L
N@NOROBOT!C$ dur!ng @ $!ngle d!ge$t!on cycle, progre$$!vely reduc!ng the morcell@te
to monore$!due @m!no @c!d$, mononucleot!de$, glycerol, free f@tty @c!d$ @nd $!mple
$ug@r$, u$!ng @n @ppropr!@te @rr@y of molecul@r $ort!ng rotor$. The$e b@$!c
molecule$ @re then h@rmle$$ly d!$ch@rged b@ck !nto the blood$tre@m through the
exh@u$t port @t the re@r of the dev!ce, complet!ng the 30-$econd d!ge$t!ocycle.

When tre@tment !$ f!n!$hed, the doctor m@y tr@n$m!t @n ultr@$ound $!gn@l to tell the
c!rcul@t!ng m!crob!vore$ th@t the!r work !$ done. The n@no-robot$ then ex!t the body
through the k!dney$ @nd @re excreted w!th the ur!ne !n due cour$e. The m!crob!vore need$
@ v@r!ety of extern@l @nd !ntern@l $en$or$ to complete !t$ t@$k$. Extern@l $en$or$ !
nclude chem!c@l $en$or$ for gluco$e, oxygen, c@rbon d!ox!de, @nd $o forth, up to 10 d!
fferent molecul@r $pec!e$ w!th 100 $en$or$ per molecul@r $pec!e$. Pre$$ure $en$or$ for
@cou$t!c commun!c@t!on @re mounted w!th!n the n@no-robot hull to perm!t the m!crob!
vore to rece!ve extern@l !n$truct!on$ from the @ttend!ng phy$!c!@n dur!ng the cour$e of !n

21
v!vo @ct!v!t!e$.

22
Ten (redund@nt) !ntern@l temper@ture $en$or$ c@p@ble of detect!ng 0.31C temper@ture
ch@nge [1!] @re po$!t!oned ne@r e@ch of the 10 !ndependent powerpl@nt$. M!crob!vore$
u$e blood$tre@m gluco$e for power l!ke re$p!rocyte$, but @l$o u$e blood-d!$$olved
oxygen wh!ch !$ @v@!l@ble only @t much lower concentr@t!on$ th@n !n the lung c@p!
ll@ry bed, $o m@ny more molecul@r $ort!ng rotor$ for O2 mu$t be pre$ent on the m!crob!
vore hull. The m!crob!vore !$ $c@led for @ m@x!mum power output of 200 pW, @bout
1000 t!me$ h!gher th@n for the re$p!rocyte. D!@mondo!d mech@n!c@l c@ble$ m@y
tr@n$m!t !ntern@l mech@n!c@l energy @t power den$!t!e$ of B6 1012W/m3 [1x]. To
connect every powerpl@nt w!th e@ch of !t$ 9 ne!ghbor$ v!@ power c@ble$, perm!tt!ng
r@p!d lo@d $h@r!ng @mong @ny p@!r of powerpl@nt$ !n$!de the dev!ce, requ!re$ 45
power c@ble$; @$$um!ng 1000 !ntern@l power c@ble$ to @ccommod@te @dd!t!on@l
power d!$tr!but!on t@$k$ @nd for redund@ncy, tot@l power c@ble volume !$ 0.05 m!cron3
.
By v@ry!ng the c@ble rot@t!on r@te, the $@me power c@ble$ c@n $!mult@neou$ly be
u$ed to convey nece$$@ry !ntern@l oper@t!on@l !nform@t!on !nclud!ng $en$or d@t@
tr@ff!c @nd control $!gn@l$ from the computer$. @ hum@n neutroph!l, the mo$t common
type of leukocyte or wh!te cell, c@n c@pture @nd engulf @ m!crobe !n @ m!nute or le$$,
but complete d!ge$t!on @nd excret!on of the org@n!$m’$ rem@!n$ c@n t@ke @n hour or
longer. Thu$ our n@tur@l wh!te cell$—even when @!ded by @nt!b!ot!c$—c@n $omet!me$
t@ke week$ or month$ to completely cle@r b@cter!@ from the blood$tre@m. By comp@r!
$on, @ $!ngle ter@bot (1012-n@norobot) do$e of m!crob!vore$ $hould be @ble to fully el!
m!n@te bloodborne p@thogen$ !n ju$t m!nute$ or hour$, even !n the c@$e of loc@lly den$e
!nfect!on$.

Th!$ !$ @ccompl!$hed w!thout !ncre@$!ng the r!$k of $ep$!$ or $ept!c $hock bec@u$e @ll
b@cter!@l component$ (!nclud!ng @ll cell-w@ll LP$) @re !ntern@l!zed @nd fully d!
ge$ted !nto h@rmle$$ non@nt!gen!c molecule$ pr!or to d!$ch@rge from the dev!ce. No
m@tter th@t @ b@cter!um h@$ @cqu!red mult!ple drug re$!$t@nce to @nt!b!ot!c$ or to
@ny other tr@d!t!on@l tre@tment—the m!crob!vore w!ll e@t !t @nyw@y. M!crob!vore$
would be up to B1000 t!me$ f@$ter-@ct!ng th@n @nt!b!ot!c-@!ded n@tur@l leukocyte$.
The n@norobot$ would d!ge$t B100 t!me$ more m!crob!@l m@ter!@l th@n @n equ@l
volume of n@tur@l wh!te cell$ could d!ge$t !n @ny g!ven t!me per!od, @nd would h@ve
f@r gre@ter m@x!mum l!fet!me c@p@c!ty for ph@gocyto$!$ th@n n@tur@l wh!te blood
cell$.

Be$!de$ !ntr@venou$ b@cter!@l, v!r@l, fung@l, @nd p@r@$!t!c $c@veng!ng, m!crob!

vore$ or rel@ted dev!ce$ could @l$o be u$ed to help cle@r re$p!r@tory or cerebro$p!n@l
b@cter!@l !nfect!on$, or !nfect!on$ !n other non$@ngu!nou$ flu!d $p@ce$ $uch @$
pleur@l , $ynov!@l, or ur!n@ry flu!d$; el!m!n@te b@cter!@l toxem!@$ @nd b!of!lm$;
er@d!c@te v!r@l, fung@l, @nd p@r@$!t!c !nfect!on$; d!$!nfect $urf@ce$, food$tuff$, or
org@n!c $@mple$; @nd help cle@n up b!oh@z@rd$ @nd tox!c chem!c@l$.

23
Rel@ted n@norobot$ w!th enh@nced t!$$ue mob!l!ty could be progr@mmed to qu!ckly
recogn!ze @nd d!ge$t even the t!n!e$t @ggreg@te$ of e@rly tumor cell$ w!th unm@tched
$peed @nd $urg!c@l prec!$!on, el!m!n@t!ng c@ncer. $!m!l@r n@norobot$ of th!$ cl@$$
could be progr@mmed to remove c!rcul@tory ob$truct!on$ !n ju$t m!nute$, qu!ckly re$cu!
ng even the mo$t comprom!$ed $troke v!ct!m from ne@r-cert@!n !$chem!c br@!n
d@m@ge, @nd could h@ve other u$e$ !n v@r!ou$ veter!n@ry @nd m!l!t@ry @ppl!c@t!
on$.

24
 CH@PTER 5
$EN$OR$ OF M!CROB!VORE$
5.1 V@R!OU$ $EN$OR$ OF M!CROB!VORE$
The m!crob!vore need$ @ v@r!ety of extern@l @nd !ntern@l $en$or$ to complete !t$
t@$k$. Extern@l $en$or$ !nclude chem!c@l $en$or$ for gluco$e, oxygen, c@rbon d!ox!de,
@nd $o forth, up to 10 d!fferent molecul@r $pec!e$ w!th 100 $en$or$ per molecul@r $pec!
e$. E@ch 10 nm × 45 nm × 45 nm chem!c@l concentr@t!on $en$or w!th 450 nm2 f@ce
@re@ !$ @$$umed to d!$cr!m!n@te concentr@t!on d!fferent!@l$ of ~10% @nd d!$pl@ce
~105 nm3 of !ntern@l n@norobot volume .T@k!ng chem!c@l $en$or energy co$t @$ ~10
zJ/count w!th ~104 count$/re@d!ng then 10 re@d!ng$/$ec by e@ch of 1000 m!crob!vore
$en$or$ g!ve$ @ m@x!mum $en$or power requ!rement of ~1 pW by @ chem!c@l $en$or
f@c!l!ty th@t d!$pl@ce$ @ tot@l of ~0.1 m!cron3 of dev!ce volume @nd 0.45 m!cron2 of
dev!ce $urf@ce @re@.

@cou$t!c commun!c@t!on $en$or$ mounted w!th!n the n@norobot hull perm!t the m!
crob!vore to rece!ve extern@l !n$truct!on$ from the @ttend!ng phy$!c!@n dur!ng the
cour$e of !n v!vo @ct!v!t!e$. @$$um!ng (21 nm)3 pre$$ure tr@n$ducer$ , then 1000 of
the$e tr@n$ducer$ d!$pl@ce ~0.01 m!cron3 of dev!ce volume @nd 0.44 m!cron2 of dev!ce
$urf@ce @re@, produc!ng @ $m@ll net power !nput to the dev!ce of ~10-4 pW when dr!
ven by cont!nuou$ 0.1-@tm pul$e$

@n !ntern@l temper@ture $en$or c@p@ble of detect!ng 0.3°C temper@ture ch@nge

m@y h@ve @ volume of (~46 nm)3 ~ 10-4 m!cron3; po$!t!on!ng ten $uch $en$or$ ne@r
e@ch of the 10 !ndependent power pl@nt$ for redund@ncy !mpl!e$ @ tot@l !ntern@l
temper@ture $en$or volume of ~0.01 m!cron3. @n @dd!t!on@l 0.03 m!cron3 of un$pec!f!
ed !ntern@l $en$or$ @re !ncluded !n the m!crob!vore de$!gn, br!ng!ng the tot@l for @ll
$en$or$ to 0.15 m!cron3.

Drug molecule$ could be purpo$ely del!vered to one cell, but not to @n @dj@cent cell, !n
the $@me t!$$ue. To fully @pprec!@te the $cope of th!$ future development !t !$ helpful
to br!efly rev!ew $ome of the b@ckground @nd recent h!$tory of med!c@l n@no-
robot!c$. N@no-med!c!ne offer$ the pro$pect of powerful new tool$ for the tre@tment of
hum@n d!$e@$e$ @nd the @ugment@t!on of hum@n b!olog!c@l $y$tem$.
D!@mond-b@$ed med!c@l n@no-robot!c$ m@y offer $ub$t@!n@l !mprovement$ !n
c@p@b!l!t!e$ over n@tur@l b!olog!c@l $y$tem$, exceed!ng even the !mprovement$ po$$!
ble v!@ t!$$ue eng!neer!ng@ndb!otechnology.
The @n@ly$!$ here focu$e$ on @ rel@t!vely $!mple dev!ce: @n !ntr@venou$ (!.V.) m!
crob!vore who$e pr!m@ry funct!on !$ to de$troy m!crob!olog!c@l p@thogen$ found !n the
hum@n blood$tre@m, u$!ng the “d!ge$t @nd d!$ch@rge protocol.

25
5.2 TRE@TMENT W!TH M!CROB!VORE$:
!f the p@t!ent pre$ent$ w!th @ $ept!c cond!t!on before the m!crob!vore$ @re !ntroduced, @
$ub$t@nt!@l preex!$t!ng concentr@t!on of !nfl@mm@tory cytok!ne$ w!ll l!kely be pre$ent
@nd mu$t be extr@cted from the blood !n concert w!th the pr!m@ry @nt!b@cter!@l m!
crob!vore tre@tment. @ll unw@nted cytok!ne molecule$ m@y be r@p!dly @nd $y$tem!
c@lly extr@cted from the blood u$!ng @ mode$t do$e of re$p!rocyte-cl@$$ n@nodev!ce$
$uch @$ ph@rm@cyte$, @ comb!n@t!on-tre@tment @ppro@ch prev!ou$ly $ugge$ted
el$ewhere .

$pec!f!c@lly, @ 1-ter@bot !ntr@venou$ do$e of m!cron-$!ze ph@rm@cyte$ e@ch h@v!ng

~105 cytok!ne-$pec!f!c molecul@r $ort!ng rotor$ @nd ~0.5 m!cron3 of onbo@rd $tor@ge
c@p@c!ty could reduce the blood concentr@t!on of ~20 kD@ !L-1bet@ @nd !L-6 cytok!ne$
from LP$-elev@ted level$ of ~100 ng/ml (~3 x 10- 9 molecule$/nm3) down to norm@l $erum
level$ of ~10 pg/ml (~3 x 10- 13 molecule$/nm3) @fter only ~200 $ec of d!ffu$!on-l!m!ted
pump!ng, u$!ng ju$t ~0.1% of the @v@!l@ble onbo@rd $tor@ge volume. (Extr@ct!ng @n
@dd!t!on@l ~105 ng/ml of LP$ from the blood$tre@m would t@ke @ $!m!l@r @mount of
t!me @nd u$e ~100% of the @v@!l@ble onbo@rd $tor@ge volume.)

F!G 5.1 M!CROB!VORE$ @$ WH!TE BLOOD CELL$

!t !$ @n !de@l n@notechnology-b@$ed drug del!very $y$tem wh!ch !$—$elf- powered,

computer-controlled med!c@l n@norobot $y$tem c@p@ble of d!g!t@lly prec!$e tr@n$port, t!
m!ng, @nd t@rgeted del!very of ph@rm@ceut!c@l @gent$ to $pec!f!c cellul@r @nd

26
!ntr@cellul@r de$t!n@t!on$ w!th!n the hum@n body. M!crob!vore$ w!ll h@ve m@ny
@ppl!c@t!on$ !n n@nomed!c!ne $uch @$ !n!t!@t!on of @popto$!$ !n c@ncer cell$ @nd d!
rect control of cell $!gn@l!ng proce$$.

To $t@rt w!th, !t would be t@rget@ble not ju$t to $pec!f!c t!$$ue$ or org@n$, but to !nd!v!
du@l cellul@r @ddre$$e$ w!th!n @ t!$$ue or org@n. @ltern@t!vely, !t would be
t@rget@ble to @ll !nd!v!du@l cell$ w!th!n @ g!ven t!$$ue or org@n th@t po$$e$$ed @
p@rt!cul@r ch@r@cter!$t!c (e.g., @ll c@ncer cell$, or @ll b@cter!@l cell$ of @ def!n!te
$pec!e$, etc.). Th!$ !de@l veh!cle would be b!ocomp@t!ble @nd v!rtu@lly 100% rel!@ble,
w!th @ll drug molecule$ be!ng del!vered only to the de$!red t@rget cell$ @nd none be!ng
del!vered el$ewhere $o th@t unw@nted $!de effect$ @re el!m!n@ted. The !de@l veh!cle
would rem@!n under the cont!nuou$ control of the $uperv!$!ng phy$!c!@n, !nclud!ng po$t-
@dm!n!$tr@t!on. Even @fter the veh!cle$ h@d been !njected !nto the body, the doctor
would $t!ll be @ble to @ct!v@te or !n@ct!v@te them remotely, or @lter the!r mode of
@ct!on or oper@t!on@l p@r@meter$. Once tre@tment w@$ completed, @ll of the veh!
cle$ could be removed !nt@ct from the body, le@v!ng no tr@ce of the!r pre$ence.

To $t@rt w!th, !t would be t@rget@ble not ju$t to $pec!f!c t!$$ue$ or org@n$, but to !nd!v!
du@l cellul@r @ddre$$e$ w!th!n @ t!$$ue or org@n. @ltern@t!vely, !t would be
t@rget@ble to @ll !nd!v!du@l cell$ w!th!n @ g!ven t!$$ue or org@n th@t po$$e$$ed @
p@rt!cul@r ch@r@cter!$t!c (e.g., @ll c@ncer cell$, or @ll b@cter!@l cell$ of @ def!n!te
$pec!e$, etc.). Th!$ !de@l veh!cle would be b!o-comp@t!ble @nd v!rtu@lly 100% rel!@ble,
w!th @ll drug molecule$ be!ng del!vered only to the de$!red t@rget cell$ @nd none be!ng
del!vered el$ewhere $o th@t unw@nted $!de effect$ @re el!m!n@ted.

The !de@l veh!cle would rem@!n under the cont!nuou$ control of the $uperv!$!ng phy$!c!
@n, !nclud!ng po$t-@dm!n!$tr@t!on. Even @fter the veh!cle$ h@d been !njected !nto the
body, the doctor would $t!ll be @ble to @ct!v@te or !n@ct!v@te them remotely, or @lter
the!r mode of @ct!on or oper@t!on@l p@r@meter$. Once tre@tment w@$ completed, @ll
of the veh!cle$ could be removed !nt@ct from the body, le@v!ng no tr@ce of the!r pre$ence.
Let’$ c@ll th!$ hypothet!c@l !de@l drug del!very veh!cle @ “m!crob!vore.” M!crob!vore$
@re be!ng $elf-powered, computer-controlled n@no-robot!c $y$tem$ c@p@ble of d!g!t@lly
prec!$e tr@n$port, t!m!ng, @nd t@rgeted del!very of ph@rm@ceut!c@l @gent$ to $pec!f!c
cellul@r @nd !ntr@cellul@r de$t!n@t!on$ w!th!n the hum@n body.

27
 CH@PTER 6

@PPL!C@T!ON$
6.1 @PPL!C@T!ON$ OF M!CROB!VORE$

Tr@p @nd Ret@!n: M!crob!vore$ could be de$!gned to tr@p @nd ret@!n (w!thout d!
ge$t!ng) $@mple$ of unknown m!crobe$ found flo@t!ng !n the blood$tre@m, when
tho$e m!crobe$ f@ll w!th!n @ cert@!n phy$!c!@n-$pec!f!ed $!ze r@nge @nd @re conf!
rmed not to be pl@telet$ or chylom!cron$. The$e $@mple$ could then be returned to the
@ttend!ng phy$!c!@n for further !nve$t!g@t!on, follow!ng n@n@phere$!$.

D!$!nfect object$: R@ng!ng $t!ll further @f!eld, m!crob!vore-der!ved dev!ce$ could be

employed !n veter!n@ry @nd m!l!t@ry @ppl!c@t!on$; to d!$!nfect $urf@ce$, object$,
@nd volume$ (e.g., 102-105 CFU/ml b@cter!@ found !n the $!nk flu!d of w@$hb@$!n
dr@!n$ !n @ ped!@tr!c w@rd ) or to $ter!l!ze org@n!c $@mple$ or ed!ble food$tuff$; to
cle@n up b!oh@z@rd$, b!opolluted dr!nk!ng w@ter, tox!c b!ochem!c@l’$, or other env!
ronment@l org@n!c m@ter!@l$ $p!ll$, @$ !n b!oremed!@t!on; @nd !n m@ny other
u$eful @ppl!c@t!on$.

6.2 U$E$ !N MED!C!NE

!n ne@r future, n@nobot$ w!ll pl@y @n !mport@nt role !n med!c!ne, l!ke @
“n@nodoctor” !n$!de the body. The c@ncer tre@tment h@$ @ $pec!@l !ntere$t bec@u$e
!$ one of the le@d!ng c@u$e$ of de@th !n the world.The n@nobot w!ll move !
ndependently @round the body @nd detect @ c@ncer cell. Therefore, when @re !n$!de or
!nter@ct!ng w!th the c@ncer cell$ they w!ll rele@$e the drug. !n th!$ w@y, the $!de
effect$ of @nt!-c@ncer drug$ on other p@rt$ of the body w!ll be reduced !n @dd!t!on to
the c@ncer drug @tt@ck, $ome n@no$c@le robot$ c@n de$troy c@ncer cell$ through
therm@l necro$!$ when @ non-!nv@$!ve extern@l $ource of he@t!ng or $t!mulu$ w!ll be
@ppl!ed. @$ ex@mple, $uper m@gnet!c be@d$ th@t c@n penetr@te @nd de$troy
c@ncerou$ t!$$ue$ w!th @ m@gnet!c f!eld

28
 F!gure 6.1 @ppl!c@t!on for c@ncer t@rget!ng tre@tment.

For @thero$clero$!$ @nd other c@rd!ov@$cul@r d!$e@$e$ $uch @$ !$chem!c or

@rrhythm!@$, n@nobot$ w!ll be !njected !nto the c!rcul@tory $y$tem by !ntr@venou$ !
nfu$!on techn!que$, for @ct!ng @g@!n$t f@tty depo$!t$. !n @dd!t!on, n@nobot$ @re
@l$o @ propo$@l for d!@gno$!$ @nd tre@tment of demyel!n@t!on, $!nce they c@n
re@ch the l@yer of myel!n !n the nerve$. @l$o, $pec!f!c n@nobot$ th@t detect @lzhe!
mer'$ d!$e@$e b@$ed on the @mylo!d prote!n β depo$!t$ Dent!frobot$ @re e$pec!@l
n@nobot$ $ugge$ted for u$e !n odontology. They could be @ complement of the
mouthw@$h or toothp@$te @nd b@$!c@lly, the!r funct!on$ w!ll con$!$t !n the met@bol!
z@t!on of the tr@pped m@ter!@l @nd !n the !dent!f!c@t!on @nd de$truct!on of
p@thogen!c b@cter!@ !n$!de of the mouth N@nobot$ c@n @l$o be u$ed to tr@vel
through the p@t!ent'$ g!ng!v@, @nd thu$ they w!ll del!ver the @n@lge$!c to the t@rget
$!te !t !$ expected $urger!e$ @t n@no level !n the ret!n@ @nd $urround!ng membr@ne$
@nd pregn@nt women. @l$o, !n gene ther@py comp@r!ng two DN@ ch@!n$; $en$!ng
prote!n$ !n$!de the cell @nd repl@c!ng chromo$ome$ The @ppl!c@t!on$ of n@nobot$ !n
med!c!ne @re m@ny @nd d!ver$e.
6.2.1 B!OMMET!C$
@n ex@mple of b!om!met!c der!v@ted n@nobot$ @re the m!crob!vore$; $!m!l@r to wh!
te blood cell$ !n the blood$tre@m. They @re thought to b!nd to @ $pec!f!c t@rget
$urf@ce $!te, @nd next to de$troy the p@thogen. @$ @ re$ult, @m!no @c!d re$!due$,
f@tty @c!d$, $!mple $ug@r$ @re rele@$ed, @mong other$.1 @ $econd ex@mple of b!
om!met!c n@nobot$ @re the re$p!rocyte$. They @re @ k!nd of @rt!f!c!@l red blood cell.
They w!ll h@ve the c@p@c!ty of pump!ng 3 m!ll!on molecule$ of O2 @nd CO2, wh!ch
repre$ent$ @ del!very of oxygen to t!$$ue$ per un!t volume 200 t!me$ h!gher th@n
n@tur@l red blood cell. The re$p!rocyte$ @re pl@nned to tre@t @nem!@ @nd lung
problem$. Other ex@mple @re the b!obot$, they @re genet!c@lly mod!f!ed b@cter!@. !t$
genet!c m@ter!@l w!ll be removed @nd repl@ced by @n @rt!f!c!@lly $ynthe$!zed
DN@. The funct!on of the$e b!olog!c@l robot$ !$ to $upply or coll@bor@te !n the p@t!
ent'$ met@bol!c need$, !.e. !n the product!on of hormone$, v!t@m!n$, enzyme$, @nd
@l$o !n the @b$orpt!on of tox!n$. !t !$ !mport@nt to ment!on th@t for th!$ c@$e, !n 2003
the f!r$t p@tent rel@ted to chem!c@l $ynthe$!$ of gene @nd gene network$ w@$ publ!
$hed.

6.2.2 P@TENT$ @ND OTHER @PPL!C@T!ON$

@ p@tent rel@ted to n@now!re motor$ fuel free w@$ @v@!l@ble $!nce 2013.There @re
two de$!gn$ of fuel-free n@nomotor$: m@gnet!c@lly @nd electr!c@lly-
propelled.@nother p@tent corre$pond$ to @ $pher!c@l n@nomotor of 50 to 90 nm !n $!ze
formed by me$oporou$ $!l!c@ @nd @ l@yer of pl@t!num on the p@rt!@l $urf@ce. The
prep@r@t!on method con$!$t$ of f!ve $tep$: $ynthe$!z!ng me$oporou$ $!l!c@

29
n@nop@rt!cle$, perform!ng hydroph!l!c tre@tment to $!l!con ch!p$, dr!pp!ng $!l!con d!
ox!de n@nop@rt!cle d!$per$!on l!qu!d onto the hydroph!l!c $!l!con ch!p$, dry!ng @nd
$putter!ng pl@t!num onto the $!l!con ch!p$, @nd f!n@lly dry!ng @fter ultr@$on!c v!
br@t!on for $h@k!ng off

@ctu@lly, the @ppl!c@t!on of n@nobot$ !n med!c!ne !$ on the f!r$t $tep$. !n 2012 @

p@tent “D!@gno$t!c-n@no$en$or @nd !t$ u$e !n med!c!ne” w@$ publ!$hed B@$!
c@lly, the object!ve of the !nvent!on w@$ to obt@!n @ new n@no$en$or for d!@gno$!$ !
n med!c!ne @nd other$ @ppl!c@t!on$, b@$ed on met@ll!c $em!conductor$ @nd
m@gnet!c n@no!$l@nd$. The $urf@ce of the$e n@nop@rt!cle$ c@n be mod!f!ed to
@ch!eve !nter@ct!on w!th the molecule of !ntere$t or recogn!ze $pec!f!c $ub$tr@te
$urf@ce @$ @ cell membr@ne. !n th@t w@y, the !nvent!on c@n be u$ed for the detect!
on of p@thogen$ or tox!n$ !n$!de the body. There @re @v@!l@ble p@tent$ @bout
n@no$en$or$ th@t could be u$ed for n@nobot$ b@$ed on @FM c@nt!lever$ @nd
m@gnet!c rel@x@t!on n@no$en$or$.

$pec!f!c@lly !n n@nobot$, $ever@l recent p@tent$ were found. Fr!t$ch et @l.propo$ed

the robo-len$. They w!ll h@ve the t@$k of mov!ng @cro$$ the corne@l $urf@ce len$
@nd remove m!croorg@n!$m$ @nd !mpur!t!e$, !mprov!ng the v!$!on of the per$on, hyg!
ene @nd dur@b!l!ty of the len$. The $econd p@tent !$ “$en$or molecul@r m@ch!ne @nd
controller @dded to progr@mm@ble n@no-robot” publ!$hed !n 2016. Th!$ !nvent!on
h@$ three p@rt$: the $en$or, the rotor @nd the controller. @ccord!ng to the p@tent “th!$ !
$ the f!r$t t!me $en$!ng !n @ $!ngle n@no-robot cre@ted by org@n!c $ynthe$!$”. The$e
n@nobot$ @re not only @ble to $en$e the env!ronment; they c@n move, be effect!ve even
under h!gh no!$e @nd e$t@bl!$h commun!c@t!on w!th extern@l dev!ce$. W!th @
controller !n$t@lled they c@n @l$o m@ke log!c@l dec!$!on$

F!gure 6. 2 Component$ of n@nobot$, f!gure mod!f!ed from M@vro!d$ et @l

Drug$ u$ed !n c@ncer tre@tment$ l!ke @ bleomyc!n or m!tomyc!n c@u$e $er!ou$ly $!de
effect$, for ex@mple: @nem!@, vom!t!ng @nd other$. $o, !n order to cre@te more eff!c!
ent c@ncer m@rker$ @nd @ch!eve @ better proce$$, @ new n@nobot w@$ developed

30
@nd p@tented !n 2016 by Zh@ng et @l. Th!$ !nvent!on !$ compo$ed of three d!fferent
p@rt$: @ lo@d!ng component, @ power component @nd @ connect!ng component. The
object!ve of th!$ !nvent!on !$ u$!ng the n@nobot @$ @ c@r to rele@$e @ l@bel!ng
re@gent @t the $pec!f!c po!nt where there !$ @ tumor. The motor of the !nvent!on !$
propelled by @TP, the p@ylo@d (l@bel!ng re@gent) could be @lph@-fetoprote!n (@FP),
c@rc!noembryon!c @nt!gen (CE@) or other tumor-$pec!f!c m@rker$. !t h@$ @n !
norg@n!c n@nom@ter!@l connect!ng component. When the n@nobot$ @rr!ve @t the
t@rget po!nt the connect!ng component w!ll be broken, @nd then the t@gg!ng re@gent
flow$ out @nd m@rk the $!ck cell$. !n th@t w@y, the doctor c@n determ!ne the d!$tr!
but!on of c@ncer cell$ @nd recogn!ze the d!$e@$e $t@tu$. !n @dd!t!on, the mo$t effect!
ve tre@tment of the d!$e@$e.

N@nobot$ w!ll h@ve $en$or$ for detect!ng level$ of gluco$e @nd, !f !t !$ nece$$@ry,
$ecrete !n$ul!n !nto the blood.Th!$ m@y be done through h$GLT3 for detect!ng gluco$e
concentr@t!on on d!@bet!c p@t!ent$, th!$ prote!n h@$ !nto !t$ funct!on$ regul@t!ng
gluco$e level$On the other h@nd, n@nobot$ th@t de$troy br@!n c@ncer cell$ were
recently $!mul@ted by Lo$crí et @l. who c@lled them N@no Bee N@no Bee$ @re @ble
to detect c@ncer cell$, de$troy them, em!t @n @cou$t!c $!gn@l when detected the tumor
@nd detect the @cou$t!c w@ve$.@l$o, the n@nodev!ce$ c@n be u$ed !n nerve $y$tem,
$pec!f!c@lly myel!n@ted d!$order$. M@ny d!$e@$e$ c@n be gener@ted @$ @ re$ult of
the lo$$ of myel!n $he@th; mult!ple $clero$!$, tr@n$ver$e myel!t!$ @nd chron!c demyel!
n@t!ng polyneurop@thy @re $ome of them. $o n@nobot$ were con$!dered be!ng @ble to
detect th!$ demyel!n@t!ng @nd eventu@lly to !mprove tre@tment procedure.

6.3 Ph@gocyt!c @ct!v!ty of M!crob!vore$

T@ble $how$ the @pprox!m@te t!mel!ne for m!crob!vore ph@gocyt!c @ct!v!ty dur!ng
@ $!ngle, complete m!crobe d!ge$t!on cycle. One m!crob!vore c@n completely d!ge$t
one m!crobe th@t !$ up to ~2 m!cron$3 !n volume -- $uch @$ @ P. @erug!no$@ b@cter!
um -- !n @ t!me td!ge$t ~ 30 $econd$. Th!$ !$ comp@r@ble to the 30-$ec P. @erug!no$@
k!ll!ng t!me of the chlor!ne d!ox!de/@mmon!@-b@$ed !ndu$tr!@l chem!c@l $ter!l@nt
Cryoc!de or the chem!c@l germ!c!de hydrogen perox!de, except th@t the m!crob!vore
@l$o prov!de$ complete d!ge$t!on of the p@thogen. (!ntr@venou$ LD50 of H2O2 !n r@t$
!$ 21 mg/kg .) L@rger m!crobe$ th@t @re ~2-4 m!cron3 !n volume could be completely !
ntern@l!zed !n ~2.5 $econd$ by t@k!ng two qu!ck "b!te$," @lthough full d!ge$t!on requ!
re$ two complete cycle$ or ~60 $econd$, @nd $t!ll l@rger m!crobe$ could be !nge$ted
@nd d!ge$ted p!eceme@l @t @ cont!nuou$ r@te of ~4 m!cron3/n@norobot-m!n, prov!
ded th@t $ome me@n$ c@n be found to @vo!d toxem!@ by en$ur!ng th@t the w@tert!
ght $e@l of @ p@rt!@lly fr@gmented org@n!$m gr@ppled @g@!n$t the n@norobot !$
m@!nt@!ned (po$$!bly u$!ng flex!ble l!poph!l!c fl@p$ or met@morph!c bumper$.
(Fung! @re l@rger th@n b@cter!@ but repl!c@te more $lowly @nd @re le$$ b!otox!c,
$o the body'$ toler@nce for m@ter!@l le@k@ge dur!ng p!eceme@l !nge$t!on of the$e
org@n!$m$ $hould be gre@ter.) The m!crob!vore con$ume$ energy @t @ m@x!mum
r@te of 200 pW, but more typ!c@lly oper@te$ @t ~100 pW.

31
 T@ble 6. M!crob!vore Proce$$!ng T!mel!ne for @ $!ngle
0.4 m!cron × 2 m!cron P$eudomon@$ @erug!no$@ B@cter!um
T!me Requ!red to El@p$ed T!
Complet!on of Event:
Complete me (m!ll!
$ec)
M!crobe @ppro@che$ the
---- 0
N@norobot
M!crob!@l Recogn!t!on @nd
0.030 m$ec 0.03
B!nd!ng
Extend Gr@pple$ 0.25 m$ec 0.28
M!crob!@l Deb!nd!ng from
0.100 m$ec 0.38
Receptor$
Tr@n$port M!crobe to !nge$t!on
3 m$ec 3.38
Port
Open !nge$t!on Port Door 0.1 m$ec 3.48
M!crobe !ntern@l!z@t!on !nto MC 1000 m$ec 1,003.48
Clo$e !nge$t!on Port Door 0.1 m$ec 1,003.58
M!nce the M!crobe !n MC 400 m$ec 1,403.58
Open MC/DC !nterch@mber Door 0.1 m$ec 1,403.68
@ct!v@te MC Eject!on p!$ton 100 m$ec 1,503.68
Clo$e MC/DC !nterch@mber Door 0.1 m$ec 1,503.78
D!ge$t M!crobe !n DC: 1 m$ec/$$c 25,743.78
Enzyme !nject!on 50 m$ec/$$c
Enzyme D!ge$t!on 50 m$ec/$$c
Enzyme Extr@ct!on

$ubtot@l
101 m$ec/$$c
× 240 $ub-$ubcycle$ ($$c) = 24,240 m$e
Open @nnul@r DC Exh@u$t Port Door 0.1 m$e 25,743.88
@ct!v@te DC Eject!on p!$ton 10 m$ec 25,753.88
Clo$e @nnul@r DC Exh@u$t Port 0.1 m$ec 25,753.98
Door

N@tur@l ph@gocyt!c cell$ @re 100-1000 t!me$ l@rger !n volume th@n m!crob!vore$
but m@y con$ume @lmo$t @$ much power dur!ng comp@r@ble @ct!v!t!e$. For
ex@mple, he@t product!on r!$e$ from 9 pW !n un$t!mul@ted hum@n neutroph!l$ up to
28 pW dur!ng ph@gocyto$!$, w!th the r!$e proport!on@l to the number of p@rt!cle$ !
nge$ted. The b@$@l r@te for re$t!ng ~400 m!cron3 T-cell lymphocyte$ !$ ~20 pW, r!$!ng
to ~65 pW dur!ng @nt!gen re$pon$e

M!crobe !nge$t!on t!me$ for n@tur@l profe$$!on@l ph@gocyte$ c@n be qu!te r@p!d,
@lthough complete d!ge$t!on @nd excret!on of the t@rget p@thogen m@y requ!re
hour$. For ex@mple, 13.8-m!cron d!@meter mur!ne bone-m@rrow m@croph@ge$
h@ve been ob$erved !nge$t!ng @ 15 m!cron p@rt!cle !n 30 m!nute$ , where@$ @n ~8-
m!cron lymphocyte w@$ !nge$ted by @ m@croph@ge !n only 3 m!nute$ w!th dr@m@t!
c $h@pe ch@nge$, !nclud!ng form@t!on of @ p$eudopod 155 m!cron$ !n length.
Neverthele$$, wh!le m@croph@ge$ c@n !nge$t up to ~25% of the!r volume per hour, m!
crob!vore$ c@n proce$$ ~2000% of the!r volume per hour, thu$ @re @bout 80 t!me$
more eff!c!ent @$ ph@gocyt!c @gent$, !n term$ of volume/$ec d!ge$ted per un!t volume
32
of ph@gocyt!c @gent.

N@tur@l profe$$!on@l ph@gocyt!c cell$ $uch @$ neutroph!l$ @l$o h@ve @ m@x!

mum c@p@c!ty for ph@gocyto$!$ dur!ng the!r $hort l!fet!me, typ!c@lly @ few hour$ !
n blood or @ few d@y$ !n t!$$ue. !n one exper!ment, 1-100 $. @ureu$ or $. f@ec@l!$
b@cter!@ were pre$ented to e@ch neutroph!l (PMN), wh!ch d!ge$ted more of them @t
the h!gher concentr@t!on$. @t the h!ghe$t concentr@t!on (100:1), PMN$ from norm@l
p@t!ent$ could only k!ll @ me@n of 9
$. @ureu$ b@cter!@ per PMN, wh!le PMN$ from c@rr!er$ of of chron!c
gr@nulom@tou$ d!$e@$e could k!ll @ me@n of 14 $. f@ec@l!$ b@cter!@ per
PMN. By comp@r!$on, @ $!ngle m!crob!vore completely d!ge$t$ ~3000 m!
crobe$/d@y of P. @erug!no$@ b@cter!@ w!th no well-def!ned m@x!mum l!fet!me
c@p@c!ty for ph@gocyto$!$.

6.4 M!crob!vore Ph@rm@cok!net!c

To crudely qu@nt!fy the @ct!v!ty of @ $pec!f!c do$e $!ze of m!crob!vore$, @ $!mple
model of m!crobe-m!crob!vore !nter@ct!on m@y be con$tructed @$ follow$.

Con$!der @ popul@t!on of m!crob!vore$ of $pher!c@l-equ!v@lent r@d!u$ RMV @nd

number den$!ty nMV (n@norobot$/m3), @nd @ $econd popul@t!on of m!crobe$ of $pher!
c@l- equ!v@lent r@d!u$ Rbug @nd number den$!ty nbug (m!crobe$/m3), $!mult@neou$ly
pre$ent !n @ flu!d comp@rtment of volume Vflu!d, temper@ture Tflu!d, @nd v!$co$!ty eflu!d.
There @re NMV = (nMVVflu!d) m!crob!vore$ @nd Nbug = (nbugVflu!d) m!crobe$ !n!t!@lly
pre$ent !n the flu!d comp@rtment.@fter $ome !ncrement@l therm@l d!ffu$!on t!me Dt
e@ch m!crobe m!gr@te$ one d!@meter @w@y from !t$ prev!ou$ po$!t!on !n the flu!d.
@ny m!crob!vore th@t !$ ent!rely pre$ent w!th!n @ r@d!u$ of (Rbug + 2RMV) of the
center of the m!crobe'$ new po$!t!on w!ll be !n coll!$!on w!th the m!crobe, hence the
prob@b!l!ty of coll!$!on !$ pcoll ~ (4/3) p nMV (Rbug + 2RMV)3 @nd the h@lf-l!fe for m!
crobe-m!crob!vore coll!$!on !$ t½ = Dt ln(½) / ln(1-pcoll) where Dt = 12 p eflu!dRbug3 / kT for
@n RM$ d!$pl@cement of one m!crob!@l d!@meter [1, L!NK]. The h@lf-l!fe for m!
crobe remov@l !$ therefore th@lf = t½Ncoll, where Ncoll !$ the number of m!crobe- m!crob!
vore coll!$!on$ requ!red to en$ure @dhe$!on @nd c@pture. Th@t !$, @fter @ t!me th@lf
h@$ el@p$ed, the f!xed popul@t!on of m!crob!vore$ h@$ el!m!n@ted h@lf of the or!g!
n@l popul@t!on of t@rget m!crobe$. Th!$ formul@t!on @$$ume$ the u$u@l
ther@peut!c $!tu@t!on where!n @ l@rge $urplu$ of n@norobot$ !$ pre$ent rel@t!ve to
the t@rget m!crobe$ (NMV >> Nbug), !n wh!ch c@$e e@ch m!crob!vore only r@rely
con$ume$ more th@n @ $!ngle m!crobe dur!ng the ther@peut!c m!$$!on t!me tm!$$!on. Th!
$ formul@t!on @llow$ u$ to !gnore the m!crob!vore ph@gocyt!c t!me td!ge$t ~ 30 $ec @$
long @$ tm!$$!on > td!ge$t.

However, m!crobe$ @re not ent!rely p@$$!ve t@rget$ for n@norobot!c d!ge$t!on. @fter
one m!crob!@l repl!c@t!on t!me trepl h@$ el@p$ed, @ll ext@nt m!crobe$ produce @ $!
ngle d@ughter m!crobe, doubl!ng the $urv!v!ng popul@t!on of m!crobe$. The f@$te$t
known b@cter!@l repl!c@tor$ h@ve @ me@n gener@t!on t!me of 900-1200 $ec. !n one
33
exper!ment, E. col! @nd P. @erug!no$@ repl!c@t!ng !n the per!tone@l c@v!t!e$ of m!
ce h@v!ng norm@l ho$t cle@r@nce mech@n!$m$ d!$pl@yed gener@t!on t!me$ of 33
m!n (1980 $ec) @nd 20 m!n (1200 $ec), re$pect!vely, dur!ng the f!r$t $t@ge$ of !nfect!
on; !n @nother exper!ment P. @erug!no$@ h@d @ doubl!ng t!me of 30-32 m!n (1800-
1920 $ec) wh!le repl!c@t!ng !n norm@l mou$e lung but only 16 m!n (960 $ec) !n
gr@nulocytopen!c (!mmune- comprom!$ed) m!ce . (Enterob@cter!@ $uch @$ E. col! d!
v!de only once every 12-24 hour$ when !n the hum@n colon (!.e., trepl = 43,200-86,400
$ec)], f@r $lower th@n the opt!m@l l@bor@tory b@tch r@te of trepl ~ 1000 $ec.)

U$!ng the$e rel@t!on$ @nd t@k!ng RMV = 1.42 m!cron$, Rbug = 0.4 m!cron$, eflu!d = 0.0011
kg/m-$ec, k = 0.01381 zJ/molecule-K (Boltzm@nn'$ con$t@nt), T = 37°C, @nd trepl ~
1000 $ec, @ m!ld b@cterem!@ w!th nbug = 0.1 ×106 CFU/ml ($ect!on 2.1.4) throughout @
blood volume of Vflu!d = 5400 cm3 !$ reduced from @n !n!t!@l b@cter!@l lo@d of Nbug =
5.4 ×108 CFU down to Nbug < 1 CFU !n ~460 $ec (~8 m!n) @t Ncoll = 1 or !n ~5400 $ec
(~1.5 hr) u$!ng @ ther@peut!c do$e of 1012 m!crob!vore$ (@ "ter@bot" do$e). @ $evere
b@cterem!@ w!th nbug = 100 ×106 CFU/ml ($ect!on 2.1.4) !$ el!m!n@ted !n ~620 $ec (~10
m!n) @t Ncoll = 1 or !n ~7300 $ec (~2 hr) @t Ncoll = 10. @ $!ngle 1-ter@bot (1012-dev!ce) !
ntr@venou$ do$e of m!crob!vore$ con$t!tute$ @ volume of ~12 cm3 of dev!ce$ @nd
produce$ @ n@nocr!t of Nct ~ 0.2% when !njected !nto @ norm@l @dult hum@n m@le
p@t!ent, @nd could l!ber@te up to 200 w@tt$ of $y$tem!c w@$te he@t wh!ch !$ very
ne@r the m@x!mum thermogen!c l!m!t for !n v!vo med!c@l n@norobot $y$tem$.

Wh!le m!crob!vore$ c@n fully el!m!n@te $ept!cem!c !nfect!on$ !n m!nute$ to hour$,

n@tur@l ph@gocyt!c defen$e$ -- even when @!ded by @nt!b!ot!c$ -- c@n $omet!me$
requ!re week$ or month$ to @ch!eve complete cle@r@nce of t@rget b@cter!@ from
the blood$tre@m ($ect!on 2.1). Thu$ m!crob!vore$ @ppe@r to be up to ~1000 t!me$
f@$ter-@ct!ng th@n e!ther n@tur@l or @nt!b!ot!c-@$$!$ted b!olog!c@l ph@gocyt!c
defen$e$. Only when the p@thogen$ @re $er!ou$ly cr!ppled c@n the n@tur@l
defen$e$ @ch!eve comp@r@ble cle@r@nce r@te$.
For ex@mple, !n one exper!ment m!ce were @ble to cle@r ~80% of @ 5000 CFU/gm
do$e of $!@l!c @c!d-def!c!ent group B $treptococc! by ph@gocyto$!$ w!th!n 1 hour,
where@$ @ l!ke number of nondef!c!ent $treptococc! $!m!l@rly pl@ced ev@ded
ph@gocyt!c k!ll!ng @nd d!$$em!n@ted to v@r!ou$ t!$$ue$.

@nother u$eful comp@r@t!ve per$pect!ve !$ th@t the @dm!n!$tr@t!on of @nt!b@cter!

@l @gent$ (e.g., @g@!n$t E. col!) typ!c@lly m@y !ncre@$e the LD50 of th@t
p@thogen by ~500-fold u$!ng @nt!b!ot!c$or ~850-fold u$!ng monoclon@l @nt!bod!e$.
For ex@mple, the m@mm@l!@n LD50 for E. col! !$ ~0.1-1 ×106 CFU/ml, r!$!ng to ~108
CFU/ml w!th the @dm!n!$tr@t!on of @nt!b!ot!c$. By employ!ng @ $u!t@ble do$e of m!
crob!vore$, @ blood$tre@m b@cter!@l concentr@t!on up to the theoret!c@l m@x!mum
of ~1011 CFU/ml (~20% of blood volume @$$um!ng ~2 m!cron3 org@n!$m$) could be
controlled, br!ng!ng @nother ~1000-fold !mprovement u$!ng n@nomed!c!ne @nd @t
l@$t extend!ng the ther@peut!c competence of the phy$!c!@n to the ent!re r@nge of
potent!@l b@cter!@l thre@t$, !nclud!ng loc@lly den$e !nfect!on$.

34
 CH@PTER 7
TECHNOLOGY U$ED

7.1 V@R!OU$ COMPUT@T!ON@L T@$K$

@n onbo@rd n@no-computer !$ requ!red to prov!de prec!$e control of @ll b@$!c m!crob!

vore oper@t!on$. The$e oper@t!on$ !nclude mo$t of the b@$!c comput@t!on@l t@$k$
@lre@dy de$cr!bed for the re$p!rocyte $uch @$ onbo@rd t@nk volume control, $en$or
coord!n@t!on, d@t@ @nd power m@n@gement, @nd n@n@phere$!$ protocol$. Other
t@$k$ un!que to the m!crob!vore !nclude m@n@gement of mult!ple rever$!ble m!crob!@l
b!nd!ng $!te$ to en$ure @ccur@te !dent!f!c@t!on of the t@rgeted m!crob!@l $pec!e$,
control of hundred$ of !ndependent gr@pple elev@tor @nd $egment rot@t!on mech@n!
$m$, coord!n@t!on of the gr@pple mot!on f!eld to tr@n$port tr@pped m!crobe$ !n @
controlled m@nner @cro$$ the n@norobot $urf@ce or for n@norobot locomot!on, @nd
$equence control for morcell@t!on @nd d!ge$t!on @ct!v!t!e$ (!nge$t!on port open!ng/clo$!
ng, m!nc!ng, tr@n$fer p!$ton!ng, enzyme cycl!ng, effluent eject!on p!$ton!ng, @nd exh@u$t
port open!ng/clo$!ng). The m!crob!vore computer !$ $c@led @$ @ 0.01 m!cron3 mech@n!
c@l n@nocomputer, !n pr!nc!ple c@p@ble of W100 meg@flop$ but norm@lly oper@ted
@t B1 meg@flop to hold power con$umpt!on to B60 pW.
@$$um!ng B5 b!t$/nm3 for n@no-mech@n!c@l d@t@ $tor@ge $y$tem$ @nd @
re@d/wr!te co$t of B10 zJ/b!t @t @ re@d/wr!te $peed of B109 b!t$/$ec, then @ comp@r!
$on w!th other $oftw@re $y$tem$ of comp@r@ble complex!ty $ugge$t$ th@t the B5
meg@b!t$ of m@$$ n@nomech@n!c@l memory needed to hold the m!crob!vore control
$y$tem d!$pl@ce$ @ volume of 0.001 m!cron3 @nd dr@w$ B10 pW wh!le !n cont!nuou$
oper@t!on. The b@$el!ne m!crob!vore de$!gn !nclude$ 10 dupl!c@te computer/memory
$y$tem$ for redund@ncy (w!th only one of the ten computer/ memory $y$tem$ !n @ct!ve
oper@t!on @t @ t!me), d!$pl@c!ng @ tot@l of 0.11 m!cron3 @nd con$um!ng r70 pW. @$
w!th re$p!rocyte$, m!crob!vore beh@v!or !$ !n!t!@lly governed by @ $et of def@ult
protocol$ m@ny of wh!ch c@n be mod!f!ed @t @ny t!me by the @ttend!ng phy$!c!@n.
B@$!c protocol$ h@ve @lre@dy been de$cr!bed for the re$p!rocyte . $!nce v!rtu@lly every
med!c@l n@norobot pl@ced !n$!de the hum@n body w!ll encounter n@tur@l ph@gocyt!c
cell$ m@ny t!me$ dur!ng !t$ m!$$!on [2d m!crob!vore$, l!ke re$p!rocyte$, m@y !
ncorpor@te @ny of $ever@l po$$!ble ph@gocyte @vo!d@nce @nd e$c@pe techn!que$
[2d], po$$!bly !nclud!ng, for ex@mple, $urf@cetethered ph@gocyte chemorepellent
molecule$ [2g, 51] or ph@gocyte engulfment !nh!b!tor$, @$ well @$ more pro@ct!ve
@ppro@che$ to ph@gocyto$!$ @vo!d@nce [2d].
M@ny $pec!@l protocol$ w!ll be needed by m!crob!vore$ but @ complete enumer@t!on !$
beyond the $cope of th!$ ch@pter. B!ocomp@t!b!l!ty-rel@ted protocol$ prov!de ex@mple$
r@ng!ng from the $!mple to the more complex. @t the $!mple end of the r@nge !$ the m!
crob!@l t@!l protocol Free rele@$e$ of b@cter!@l fl@gell@ !nto the blood$tre@m could
produce !nfl@mm@t!on or el!c!t v@r!ou$ !mmune $y$tem re$pon$e$ @nd
35
thu$ $hould be @vo!ded. Complete !ntern@l!z@t!on of t@!l m@y be en$ured by $pec!@l!
zed oper@t!on@l rout!ne$ (e.g., forced end-over-end rot@t!on of @n !ntern@l!zed m!crobe
wh!le !n$!de the morcell@t!on ch@mber, thu$ completely $pool!ng the t@!l !nto the m!crob!
vore before fully $e@l!ng the !nge$t!on port door) or by $pec!@l!zed mech@n!c@l tool$ or
j!g$ (e.g., @ counterrot@t!ng !nterd!g!t@ted-knobbed c@p$t@n-roller p@!r). @n ex@mple
of @ more complex protocol @r!$e$ from the f@ct th@t @ll bloodborne n@norobot$
l@rger th@n B1 m!cron !n @ll three phy$!c@l d!men$!on$ @re $ubject to po$$!ble
geometr!c@l tr@pp!ng !n the fene$tr@l $l!t$ of the $plen!c $!nu$o!d$ !n the red pulp of the
$pleen..

@ $m@ll percent@ge of blood !$ forced to c!rcul@te through @ phy$!c@l f!lter !n the

$pleen requ!r!ng p@$$@ge through $l!t$ me@$ur!ng 1–2 m!cron$ !n w!dth @nd B6 m!
cron$ !n length [2e]. M!crob!vore$ wh!ch become p!nned to @ $l!t f@ce-on, or wh!ch
become $tuck edge-on dur!ng @n @ttempted p@$$@ge, c@n detect th@t they h@ve
become tr@pped by me@$ur!ng v@r!ou$ blood component concentr@t!on @nd pre$$ure d!
fferent!@l$ @cro$$ the!r $urf@ce$. The n@norobot then @ct!v@te$ !t$ @utom@t!c
$plenofene$tr@l e$c@pe protocol, wh!ch !nvolve$ the exten$!on @nd p@tterned c!l!@t!on
of $urf@ce. L!ne$ of Comp@ctly Wr!tten Low-Error $oftw@re Code Requ!red to Control
Complex $em!@utonomou$ M@ch!ne$. Control $oftw@re for dev!ce E$t!m@ted l!ne$ of
code B!t$ of code (B100 b!t$/l!ne) Ref. Voy@ger $p@cecr@ft $oftw@re 3,000 300,000 V!
k!ng L@nder $oftw@re — 432,000 [46] Re$p!rocyte Control $y$tem (e$t.) — B500,000
G@l!leo $p@cecr@ft $oftw@re 8,000 800,000 C@$$!n! $p@cecr@ft $oftw@re 32,000
3,200,000 M!crob!vore Control $y$tem (e$t.) — B5,000,000 @r!@ne Fl!ght Control
$oftw@re 90,000 9,000,000 @!rbu$ 340 Fl!ght W@rn!ng $y$tem 100,000
10,000,000 M@r$ P@thf!nder $p@cecr@ft 160,000 16,000,000 $p@ce $huttle
$oftw@re 500,000 50,000,000 Boe!ng 777 @nd @!rbu$ 340 3,000,000 300,000,000
15.2. EXEMPL@R MED!C@L N@NOROBOT DE$!GN$ 405 gr@pple$ unt!l $en$or
re@d!ng$ reve@l th@t p@$$@ge through the $l!t h@$ been @ch!eved, @fter wh!ch the
gr@pple$ @re retr@cted

7.2 COMMON FUNCT!ON$ REQU!R!NG ONBO@RD COMPUT@T!ON

Funct!on$ wh!ch m@y be common to m@ny d!fferent cl@$$e$ of med!c@l n@norobot$
@nd mu$t be controlled by the onbo@rd n@nocomputer !nclude tho$e l!$ted below.

1.Pump!ng: $!ngle-molecule recogn!t!on, $ort!ng, @nd pump!ng v!@ molecul@r $ort!ng

rotor$ to @llow molecule-by-molecule exch@nge$ w!th the env!ronment. The typ!c@l B1
m!cron n@norobot m!ght h@ve B104 –105 $ort!ng rotor$ requ!r!ng !nd!v!du@l control,
though m@ny c@n prob@bly be oper@ted !n b@nk$ or clu$ter$ of 10–100 rotor$.
Molecul@r pump$ would be @ pr!m@ry $y$tem !n n@norobot$ $uch @$ ph@rm@cyte$
wh!ch @re !ntended $olely to d!$pen$e drug$ or other re@gent$.

36
2.$en$!ng: Chem!c@l $en$or$, pre$$ure @nd temper@ture $en$or$, ull@ge $en$or$ (!
nclude onbo@rd pre$$ure t@nk m@n@gement), electr!c@l, m@gnet!c @nd opt!c@l
$en$or$ , po$!t!on/or!ent@t!on $en$or$ , gr@v!ty $en$or$ , @nd molecul@r recogn!t!on $!
te$; @nd coord!n@t!on @nd !nterpret@t!on of m@cro$en$!ng d@t@ prov!d!ng onbo@rd !
nform@t!on from extern@l @cou$t!c, propr!ocept!ve, electr!c/m@gnet!c, or opt!c@l
$ource$, or d!rect neur@l tr@ff!c e@ve$dropp!ng. The typ!c@l B1 m!cron n@norobot m!ght
employ B104 –105 $en$or$ of v@r!ou$ k!nd$ requ!r!ng !nd!v!du@l control.

3.Conf!gur@t!on: Control of dev!ce $h@pe; g@$-dr!ven exten$!ble bumper$ to m@!nt@!n

phy$!c@l cont@ct @mong @dj@cent dev!ce$ dur!ng. COMMON FUNCT!ON$ REQU!R!
NG ONBO@RD COMPUT@T!ON 411 $t@t!onkeep!ng; control of !ntern@l b@ll@$t!ng
for n@n@phere$!$; @nd control of chem!c@l l!g@nd$ for hull d!$pl@y$, fl@g$, or
$em@phore$, or for controlled @dhe$!oregul@t!on of extern@l $urf@ce$.

4.Energy: Control of onbo@rd power gener@t!on or power rece!ver $y$tem$ !nclud!ng

therm@l, mech@n!c@l, @cou$t!c, chem!c@l, electr!c@l, photon!c, or nucle@r $ource$;
m@n@gement of onbo@rd energy $tor@ge; controll!ng the tr@n$duct!on, cond!t!on!ng,
@nd conver$!on of rf or tethered energy $ource$; @nd control of !ntern@l power d!$tr!but!
on @nd lo@d b@l@nc!ng throughout @ n@norobot!c dev!ce.

5.Commun!c@t!on: Control of commun!c@t!on$ h@rdw@re !nclud!ng rece!ver$ @nd

tr@n$m!tter$, whether chem!c@l, @cou$t!c, electrom@gnet!c, or other mod@l!ty; !
nterpret@t!on of rece!ved $!gn@l$ @$ new comm@nd$ from the phy$!c!@n; repl@cement
of ex!$t!ng oper@t!ng p@r@meter$ w!th new one$ (wh!le the dev!ce$ @re !n v!vo), $uch
@$ the ch@ng!ng of re$p!rocyte oper@t!ng p@r@meter$ @t h!gh @lt!tude$ or deep
underw@ter @t h!gh pre$$ure$; coord!n@t!on of !ntern@l f!ber or mob!le network$; control
of !nme$$@g!ng ($!gn@l$ from extern@l $ource$ th@t @re d!rected to !n v!vo
n@norobot$) @nd outme$$@g!ng ($!gn@l$ from !n v!vo n@norobot$ th@t @re d!rected to
extern@l rec!p!ent$), !nclud!ng coord!n@t!on of n@norobot popul@t!on$ to @ccur@tely
tr@n$fer !nform@t!on d!rectly to or from the p@t!ent (e.g., d!rectly v!@ $ome$thet!c, k!
ne$thet!c, @ud!tory, gu$t@tory, olf@ctory, ocul@r or derm@l d!$pl@y$, or !nd!rectly v!@
@rt!f!c!@l $ymptom$); @nd rout!ng of d@t@ $!gn@l$ !ntern@lly throughout the
n@norobot

6.N@v!g@t!on. E$t@bl!$h!ng @b$olute or rel@t!ve phy$!c@l po$!t!on @cro$$ m@ny

reg!me$ !nclud!ng blood$tre@m, t!$$ue$, org@n$, @nd cell$; po$!t!on@l n@v!g@t!on by
de@d reckon!ng, c@rtot@x!$, m@cro/m!crotr@n$ponder network$ (!nclud!ng $t@t!
onkeep!ng protocol$ @mong ne!ghbor!ng !ntercommun!c@t!ng dev!ce$ @nd $elf-correct!ng
c@l!br@t!on protocol$ @llow!ng B3 m!cron po$!t!on!ng @ccur@c!e$ !n B1000-dev!ce
$t@ck$ m@!nt@!n!ng B100-m!cron !nterdev!ce $ep@r@t!on$ @cro$$ 10-cm t!$$ue
column$); funct!on@l n@v!g@t!on

37
u$!ng thermogr@ph!c, b@rogr@ph!c, chemogr@ph!c, or m!crob!ot!c mod@l!t!e$; @nd
v@l!d@t!on of the !dent!ty of encountered t!$$ue type$ [1@n].

7.M@n!pul@t!on: Deployment @nd @ctu@t!on of m@n!pul@tor$ !nclud!ng c!l!@ry,

pneum@t!c, or tele$cop!ng $y$tem$; $tow@ge, retr!ev@l, $elect!on, !n$t@ll@t!on, u$e,
@nd det@chment of toolt!p$ @nd other end-effector$; m@n@gement of tool @nd m@n!
pul@tor g@r@ge$; m@n@gement of coord!n@ted m@n!pul@tor @rr@y$; @nd control of
onbo@rd d!$po$@l or d!$@$$embly $y$tem$ !nclud!ng morcell@t!on, gr!nd!ng, $on!c@t!
on, therm@l or chem!c@l decompo$!t!on $y$tem$ [1b].

8.Locomot!on: Control of $pec!f!c !n v!vo locomot!on $y$tem$ [1b!] !nclud!ng c!l!@ry or

gr@pple $y$tem$, $urf@ce deform@t!on, !ncl!ned pl@ne$/ $crew$, volume d!$pl@cement,
@nd v!$cou$ @nchor!ng $y$tem$; control of locomot!on @cro$$ cell-co@ted t!$$ue
$urf@ce$ (e.g., v@$cul@r lumen) v!@ legged @mbul@t!on, t@nk-tre@d roll!ng, @moebo!
d mot!on or !nchworm locomot!on; control of h!$ton@t@t!on (t!$$ue $w!mm!ng) @nd
cytopenetr@t!on @$ requ!red; cytoc@rr!@ge (n@norobot$ controll!ng movement of
n@tur@l cell$ $uch @$ leukocyte$ from !ntr@cellul@r berth$); @nd ex v!vo locomot!on
[1bj] !nclud!ng dent@l w@lk!ng, ep!derm@l locomot!on, @nd @!rborne n@nofl!ght.

9.Comput@t!on: Control of @ll onbo@rd computer $y$tem$ [1d] !nclud!ng CPU$,

memory, @nd !ntern@l d@t@ tr@n$m!$$!on l!ne$, @nd procedure$ for $w!tch!ng between
redund@nt computer$ or computer component$; @nd the m@n@gement, $ynchron!z@t!on
@nd c@l!br@t!on of onbo@rd clock$ @nd c@lend@r$ [1bk]. N@nocomputer$ th@t
employ $t@nd@rd d!$$!p@t!ve @rch!tecture$ (@$ oppo$ed to energy-$@v!ng rever$!ble
comput!ng @rch!tecture$ w!ll gener@te @ h!gh power den$!ty of w@$te he@t, hence
n@nocomputer$ !n l@rger n@norobot$ w!ll commonly be throttled down from m@x!mum
proce$$!ng $peed$ dur!ng norm@l oper@t!on$ both to $@ve energy @nd to @vo!d exce$$!
ve loc@l!zed dev!ce he@t!ng. Th!$ !$ @ pr!nc!p@l de$!gn l!m!t@t!on on med!c@l
n@norobot computer$. Con$equently, @ good de$!gn ph!lo$ophy !$ to offlo@d @$ m@ny
comput@t!on@l t@$k$ @$ po$$!ble to !n v!vo d@t@ proce$$!ng dev!ce$ loc@ted
extern@l to the n@norobot (e.g., f!xedloc@t!on t!$$ue- embedded !n v!vo n@norobot!c !
mpl@nted node$), or prefer@bly to l@rge ex v!vo computer$ embedded !n the phy$!c!@n’$
off!ce, the $urg!c@l $u!te, or the ho$p!t@l !nfr@$tructure, w!th d@t@ tr@n$ferred !n @nd
out of the p@t!ent’$ body through f!xed or mob!le commun!c@t!on$ network$ [1bm].

10.Redund@ncy M@n@gement: @ccept@ble $y$tem rel!@b!l!ty for popul@t!on$ of tr!ll!

on$ of cooper@t!ng med!c@l n@norobot$ w!ll requ!re exten$!ve $ub$y$tem @nd
component redund@ncy. Typ!c@lly, tenfold redund@ncy @mong m!$$!on-cr!t!c@l
component$ @ppe@r$ $uff!c!ent to en$ure @ccept@ble m!$$!on rel!@b!l!ty [12g] !n
ther@peut!c @ppl!c@t!on$. For ex@mple, @ good n@norobot de$!gn m@y $pec!fy 10 t!
me$ more $ort!ng rotor$, $en$or$, or @ppend@ge$ for locomot!on th@n @re $tr!ctly nece$
$@ry, w!th the l@rge $urplu$ held !n re$erve @$ $p@re$ @nd b@ckup$. Th!$ !mpl!e$

38
th@t @nother !mport@nt comput@t!on@l

39
funct!on w!ll be redund@nt $y$tem$ m@n@gement @nd model!ng]. Onbo@rd computer$
mu$t cont!nuou$ly mon!tor the perform@nce of @ll redund@nt component$ @nd
$ub$y$tem$ to determ!ne whether or not @ny h@ve f@!led, @nd !f $o, to dec!de wh!ch
b@ckup $y$tem to $w@p !n to repl@ce the funct!on performed by the f@!led $y$tem. $tud!
e$ @re needed to def!ne opt!m@l control protocol$ for redund@nt $y$tem$ m@n@gement.
@$ @ $!mple ex@mple, !n the c@$e of the re$p!rocyte$ wh!ch employ tenfold-redund@nt
onbo@rd gluco$e-oxygen power $t@t!on$, rel!@b!l!ty $!mul@t!on$ m@y be u$eful to
determ!ne whether @ll ten power $t@t!on$ !de@lly $hould be run: (@) @t pe@k power on
@ rot@t!ng $chedule, (b) @t p@rt!@l power on @ cont!nuou$ b@$!$, or (c) one @t @ t!me
unt!l f@!lure, there@fter $w!tch!ng to the next b@ckup. Dur!ng @ny component $w!
tchover$, the re$p!rocyte computer mu$t control the re@l-t!me d!$tr!but!on of power th@t !$
tr@n$m!tted hydr@ul!c@lly to loc@l $t@t!on $ub$y$tem$ @nd @l$o @long @ dozen !
ndependent !nter$t@t!on trunk l!ne$ th@t @llow $t@t!on$ to p@$$ hydr@ul!c power
@mong them$elve$ @$ requ!red, perm!tt!ng lo@d $h!ft!ng @nd b@l@nc!ng. Redund@ncy
m@n@gement @l$o @ppl!e$ to onbo@rd computer$, wh!ch @re them$elve$ mult!ply
redund@nt. Further @n@ly$!$ !$ needed to determ!ne the be$t techn!que$ for $@fely $w!
tch!ng @mong them w!thout $@cr!f!c!ng $y$tem rel!@b!l!ty.

11.Fl@wle$$ Comp@ct $oftw@re: @nother fund@ment@l l!m!t to onbo@rd comput!ng !$

the m!n!mum pr@ct!c@l volume th@t m@y be occup!ed by reg!$ter$ or other phy$!c@l
med!@ c@p@ble of $tor!ng or execut!ng onbo@rd d@t@ or !n$truct!on$. For ex@mple, @
1 m!cron3 $tor@ge volume could cont@!n B1010 b!t$ (B1 GB @$$um!ng 8-b!t word$) on
@ hydrofluoroc@rbon memory t@pe w!th @ m@x!mum B10 $ec @cce$$ t!me, or B107 b!
t$ (B1 MB) !n @ t!ghtly p@cked block of mech@n!c@l reg!$ter$ compr!$ed of n@no$c@le
d!@mond rod$ w!th @ m@x!mum B1 m!ll!$ec @cce$$ t!me [1@f]. G!ven the pre$umed
requ!rement$ for tenfold redund@ncy @nd the need for non-memory computer component$,
m@x!mum @llow@ble onbo@rd d@t@ $tor@ge m@y often be @n order of m@gn!tude
$m@ller th@n the @bove f!gure$, or le$$. G!ven $uch l!m!ted @v@!l@b!l!ty of onbo@rd
n@norobot computer memory, !t $eem$ !nev!t@ble th@t eff!c!ent ultr@comp@ct $oftw@re
@nd $p@ce-eff!c!ent @lgor!thm$ w!ll @g@!n come !nto vogue. $uch $oftw@re w@$
commonpl@ce !n the e@rly d@y$ of PC development when tot@l R@M memor!e$ were
often l!m!ted to 48 KB or le$$—@ me@ger @lloc@t!on th@t w@$ nonethele$$ $uff!c!ent
to hold @n ent!re word proce$$!ng progr@m.

H!gh $oftw@re rel!@b!l!ty mu$t @l$o be @ m@jor de$!gn cr!ter!on

bec@u$e med!c@l n@norobot$ mu$t be extremely rel!@ble. People h@ve @lre@dy been k!
lled or @lmo$t k!lled by $oftw@re bug$ !n convent!on@l med!c@l dev!ce$. Pol!c!e$ for
med!c@l @nd product l!@b!l!ty !n$ur@nce w!ll @lmo$t cert@!nly !ncorpor@te $tr!ct requ!
rement$ for prov@ble $oftw@re rel!@b!l!ty @nd $y$tem noncr@$h@b!l!ty @$ me@$ured
by form@l!zed !ndu$try metr!c$ bec@u$e of the potent!@l $!gn!f!c@nt r!$k$ to hum@n
he@lth !f @ n@norobot control m@lfunct!on due to $oftw@re error occur$ dur!ng
ther@peut!c u$e—@
40
$tr!ngent requ!rement th@t $hould, @t long l@$t, m@ke the form@l!zed product!on of
‘‘error- free’’ code econom!c@lly v!@ble. The rel@ted $uperv!$ory $oftw@re mu$t @l$o
be de$!gned w!th @ $!mple u$er !nterf@ce to m!n!m!ze the po$$!b!l!ty of error even when
oper@ted by we@ry, d!$tr@cted, @nd f@ll!ble hum@n med!c@l per$onnel

7.3 N@NOROBOT CONTROL PROTOCOL$

@ n@norobot control protocol !$ @ $pec!@l!zed $equence of n@norobot @ct!on$ th@t
m@y be executed !n c@refully $pec!f!ed c!rcum$t@nce$ !n order to en$ure th@t def!ned m!
$$!on !$ $ucce$$fully completed !n @n @ccur@te, $@fe, @nd t!mely m@nner @ccord!ng
to pl@n. Protocol-dr!ven @ct!on$ m@y be obl!g@te (m@nd@tory) or f@cult@t!ve (perm!$
$!ve) @$ requ!red. $uch @ct!on$ m@y be !n!t!@ted !n re$pon$e to $en$or !nput (r@ng!ng
from $!mple !nput$ $uch @$ @mb!ent temper@ture or chem!c@l concentr@t!on, to more
complex !nput$ $uch @$ detect!on of engulfment by @ ph@gocyte), clock or c@lend@r
d@tem@rk$, complet!on of !ntermed!@te m!$$!on benchm@rk$, or extern@l comm@nd$.
$!x gener@l cl@$$e$ of n@norobot control protocol$ h@ve been !dent!f!ed @nd @re
de$cr!bed below. @ll n@norobot$ w!ll requ!re $ome of the$e protocol$, @nd $ome m@y
requ!re mo$t or @ll of them.

1.Oper@t!on@l Protocol$:Oper@t!on@l protocol$ control the $!mple$t @nd mo$t b@$!c

procedure$ th@t n@norobot$ mu$t perform. $uch protocol$ m@y control the oper@t!on of !
nd!v!du@l or group$ of $en$or$ or $ort!ng rotor$, or m@y regul@te !ntern@l power
tr@n$fer @nd energy $tor@ge u$!ng log!c-br@nched feedb@ck loop$. !n the c@$e of the
re$p!rocyte, @ proper @n@ly$!$ of oper@t!on@l protocol$ would !nvolve dr@w!ng up @n
oper@t!on@l flowch@rt for !t$ norm@l beh@v!or$, !nclud!ng @ltern@te mode$, oper@t!
on@l opt!on$, p@r@meter lookup t@ble$, commun!c@t!on$ !nterf@ce$, lo@d level$, $w!
tch!ng @mong b@ckup$, !ntern@l $t@te mon!tor!ng, $en$or !ntegr@t!on w!th $ort!ng rotor
funct!on, eng!ne throttl!ng, @nd dev!ce-$pec!f!c oper@t!on@l mode$—e.g., re$t!ng, exerc!
$!ng, @$phyx!@t!ng, underw@ter, h!gh @lt!tude, @nd $o forth. @l$o !ncluded here @re
$t@nd@rd!zed u$er !nterf@ce$ @nd u$er protocol$ to m@ke !t @$ conven!ent @$ po$$!
ble for doctor$ to @cce$$ @nd reprogr@m the n@nodev!ce$ wh!le en$ur!ng p@t!ent
$@fety. The n@norobot mu$t @l$o be @ble to follow !t$ @ct!v!ty $cr!pt @nd recogn!ze
when !t$ m!$$!on h@$ ended, @nd then be conven!ently $hut down. !n the c@$e of the m!
crob!vore, the end of the m!$$!on !$ not cle@rly def!ned bec@u$e @nother t@rget m!crobe
m!ght @lw@y$ be found, hence the term!n@t!on of th!$ n@norobot’$ openended m!$$!on
mo$t l!kely w!ll be determ!ned by @ clock or w!ll be extern@lly comm@nded by the
@ttend!ng phy$!c!@n. !n other c@$e$, l!ke the chrom@llocyte, the m!$$!on $equence !$
cle@rly def!ned @nd h@$ @ $pec!f!c end $t@te bec@u$e the dev!ce c@n tr@ck !t$
progre$$ through the preprogr@mmed @ct!v!ty $cr!pt checkl!$t @$ @ funct!on of
completed t@$k$ @nd extern@l event$. @ct!v!ty $cr!pt$ m@y be the mo$t complex form of
oper@t!on@l protocol.

41
2.B!ocomp@t!b!l!ty Protocol$: Mo$t n@norobot$ m@y requ!re @ct!ve proce$$e$ to m@!
nt@!n b!ocomp@t!b!l!ty. The$e proce$$e$ w!ll requ!re computer control @nd m@y r@nge
from $!mple protocol$ $uch @$ controll!ng @lter@ble $urf@ce chem!c@l mod!f!c@t!on$
(e.g., @dhe$!oregul@t!on [2k]) @nd the m!crob!@l t@!l protocol to rel@t!vely complex
proce$$e$ $uch @$ ph@gocyte @vo!d@nce @nd e$c@pe protocol$ [2d] or the
$plenofene$tr@l e$c@pe protocol (for bloodborne n@norobot$ @bove @ cert@!n $!ze),
@ct!v@t!on of wh!ch w!ll !n!t!@te @ $tereotyped $et of locomot!ve movement$
N@NOROBOT CONTROL PROTOCOL$ 415 th@t re$ult !n bre@k!ng free from $plen!c
c@pt!v!ty @nd return!ng to the blood$tre@m .Numerou$ other b!ocomp@t!b!l!ty $!tu@t!
on$ requ!r!ng $pec!@l!zed protocol$ @re !dent!f!ed el$ewhere. One !ntere$t!ng ex@mple !
nvolve$ the comm@ndeer!ng of n@tur@l mot!le cell$ by med!c@l n@norobot$, @
procedure known @$ cytoc@rr!@ge [1bn], @$ @n @ltern@t!ve mode of !n v!vo tr@n$port.

Dur!ng cytoc@rr!@ge, one or more med!c@l n@norobot$ m@y enter @ mot!le cell, r!de or
$teer the cell to @ de$!red de$t!n@t!on !n$!de the hum@n body, then v@c@te the cell upon
@rr!v@l. When m@croph@ge$ @nd other leukocyt!c cell$ become !nfected, they expre$$
B7 on the!r membr@ne $urf@ce wh!ch c@n be recogn!zed by @ T-cell CD28 receptor
prote!n, tr!gger!ng @n !mmunolog!c re$pon$e. !n the ‘‘!nfected cytoveh!cle protocol,’’
n@norobot p!lot$ would !n$pect the cell $urf@ce of @ pro$pect!ve cytoveh!cle$ for B7 @nd
$!m!l@r fl@g$ pr!or to cytopenetr@t!on to @vo!d choo$!ng @n !nfected cell for cytoc@rr!
@ge th@t could then $pre@d the !nfect!on. !f the cell $ub$equently become$ !nfected @nd
beg!n$ expre$$!ng B7 or other w@rn!ng $ub$t@nce$ dur!ng the journey, the protocol would
d!rect the n@norobot p!lot to @bort the m!$$!on @nd $teer the cytoveh!cle to @ ne@rby d!
$po$@l $!te, or !mplement !mmed!@te ther@peut!c me@$ure$; f@!l!ng th!$, the p!lot
$hould @b@ndon the veh!cle @t once.

3.The@ter Protocol$ @ the@ter protocol !$ @ control proce$$ by wh!ch the n@norobot

ver!f!e$ th@t !t !$ perform!ng !t$ t@$k$ !n the !ntended loc@t!on or !n the de$!red c!
rcum$t@nce$, @$ pre$cr!bed by the @ttend!ng phy$!c!@n. !f the n@norobot determ!ne$
th@t !t$ pre$ent loc@t!on !$ !n@ppropr!@te or the nece$$@ry cond!t!on$ to en@ble @ct!
on no longer ex!$t, the protocol tr!gger$ @n @ppropr!@te correct!ve or defen$!ve re$pon$e.
When @ n@norobot detect$ @n out-of-the@ter cond!t!on (e.g., bled out of body), the mo$t
@ppropr!@te re$pon$e m@y often be to $@fe the dev!ce @nd then $hut down. $ub$equent
reentry !nto the@ter @fter $hutdown (e.g., bled-out dev!ce$ f!nd the!r w@y b@ck !nto the
blood$tre@m) norm@lly $hould not @llow re@ct!v@t!on of the dev!ce bec@u$e dur!ng !t$
@b$ence from the@ter, the n@norobot m@y h@ve been $ubjected to unknown force$,
chem!c@l$, r@d!@t!on, or even reprogr@mm!ng th@t could render !t h@rmful to the p@t!
ent upon reentry, !f re@ct!v@ted. Even !f @ full pre-re$t@rt $elf-d!@gno$t!c rout!ne could
be performed @fter @n out-of-the@ter excur$!on, unw@nted mod!f!c@t!on$ m@y be too
$ubtle to detect v!@ !ntern@l $en$or$ @nd the r!$k of m@l!c!ou$ t@mper!ng !$ too gre@t.
One po$$!ble except!on !$ where the v!ol@ted the@ter of oper@t!on !$ @ funct!on@l cond!
t!on $uch @$
42
‘‘p@t!ent !$ @$leep,’’ ‘‘p@t!ent !$ drunk,’’ or ‘‘p@t!ent !$ $exu@lly @rou$ed.’’ !n the$e
c@$e$, !t !$ le$$ l!kely th@t $w!tch!ng on or off !n re$pon$e to the@ter protocol$ would
po$e $!gn!f!c@nt r!$k e!ther to the dev!ce$ or to the p@t!ent bec@u$e the$e cond!t!on$ @re
norm@lly cycl!c@l vol!t!on@l $t@te$ th@t def!ne !nherently ephemer@l or per!od!c
the@ter$ of @ct!on. The longer @ ther@peut!c n@norobot!c med!c@l procedure t@ke$ to
complete, the more t!me$ @ the@ter protocol $hould be executed dur!ng the m!$$!on.

Protocol$ m!ght be checked more or le$$ frequently depend!ng upon the!r m!$$!on cr!t!c@l!
ty, the!r !mp@ct on $@fety, the l!kel!hood of @ r@p!d ch@nge !n $t@tu$, the!r comput@t!
on@l overhe@d (the more often the protocol !$ run, the fewer computer re$ource$ @re
@v@!l@ble for pr!m@ry t@$k$), @nd d@t@ @cqu!$!t!on t!me (e.g., detect!ng @ very
r@re molecule !n the blood$tre@m m!ght t@ke m@ny $econd$ or m!nute$; the reprotocol
cycle t!me $hould be $!gn!f!c@ntly longer th@n the m@x!mum pr@ct!c@l $en$!ng per!od).
$ome protocol$ m!ght be checked cont!nuou$ly—b!ochem!c@l proce$$e$ m@y occur !n m!
ll!$econd$, other b!olog!c@l re$pon$e$ m@y requ!re $econd$ or m!nute$ (e.g., @utomob!le
fuel g@uge$ @re rechecked electron!c@lly @bout once every $econd.) !t !$ worth not!ng
th@t the@ter protocol$ @re found !n n@tur@l hum@n cell b!ology. For ex@mple, mo$t t!$
$ue cell$ requ!re @tt@chment to the ECM @nd $ub$equent $pre@d!ng on the ECM, for
proper growth, funct!on, @nd even $urv!v@l, @ fe@ture known @$ @nchor@ge
dependence
.Upon lo$!ng th!$ @nchor@ge @nd dep@rt!ng from the de$!red the@ter of oper@t!on, cell$
often d!e by undergo!ng @popto$!$ or progr@mmed cell de@th. (Only the cell$ c!rcul@t!ng
!n the blood @re de$!gned to $urv!ve w!thout @tt@chment @nd $pre@d!ng—$ome tumor
cell$ @cqu!re th!$ @b!l!ty @nd le@ve the!r or!g!n@l t!$$ue $!te to form met@$t@$e$, @
p@tholog!c@l $t@te.) !n th!$ the@ter protocol, the cell !$ de$!gned to def@ult to $u!c!de,
but defer$ th!$ @ct!on @$ long @$ @ $urv!v@l $!gn@l !$ rece!ved, !nd!c@t!ng cont!nued
re$!dence !n the perm!tted the@ter of oper@t!on$. The $urv!v@l $!gn@l !$ gener@ted @$
long @$ the cell m@!nt@!n$ !ntegr!n @tt@chment to @ b@$ement $urf@ce or ECM. Th!$
protocol tr!gger !$ c@lled @n @poptot!c $w!tch .T-cell$ employ @ $!m!l@r the@ter
protocol v!@ the ‘‘!mmunolog!c@l $yn@p$e’’ .

4.$@fety Protocol$: $@fety eng!neer!ng !nvolve$ m@k!ng $ure th!ng$ do not f@!l !n the
pre$ence of r@ndom f@ult$. @$ Dorner note$ th@t le@rn!ng theory tell$ u$ [th@t] bre@k!
ng $@fety rule$ !$ u$u@lly re!nforced, wh!ch !$ to $@y, !t p@y$ off. !t$ !mmed!@te
con$equence !$ only th@t the v!ol@tor !$ r!d of the encumbr@nce the rule$ !mpo$e @nd
c@n @ct more freely. $@fety rule$ @re u$u@lly dev!$ed !n $uch @ w@y th@t @ v!ol@tor
w!ll not be !n$t@ntly blown $ky h!gh, !njured, or h@rmed !n @ny other w@y but w!ll !
n$te@d f!nd th@t h!$ l!fe !$ m@de e@$!er. The po$!t!ve con$equence$ of v!ol@t!ng
$@fety rule$ re!nforce our tendency to v!ol@te them, $o the l!kel!hood of @ d!$@$ter !
ncre@$e$. @nd when one doe$ !n f@ct occur, the v!ol@tor of $@fety rule$ m@y not h@ve
@nother ch@nce to mod!fy h!$ beh@v!or !n the future.

43
5.$ecur!ty Protocol$ :Even the be$t $ecur!ty c@nnot prevent @ll h@rm but c@n help @vo!
d $!gn!f!c@nt h@rm wh!le @llow!ng the $y$tem to cont!nue oper@t!ng norm@lly. Wh!le
mo$t fe@ture$ @re u$eful for wh@t they do, $ecur!ty fe@ture$ w!th!n product$ @re u$eful
bec@u$e of wh@t they don’t @llow to be done. $ecur!ty eng!neer!ng help$ to en$ure th@t
the n@nodev!ce w!ll not f@!l ‘‘!n the pre$ence of @n !ntell!gent @nd m@l!c!ou$
@dver$@ry who force$ f@ult$ @t the wor$t t!me @nd !n the wor$t w@y.’’ $ecur!ty
protocol$ @re requ!red to en$ure th@t !ncom!ng comm@nd$ or!g!n@te from tru$ted @nd
@uthor!zed $ource$, @nd m@y employ check$um$, $!gned @nd cert!f!ed progr@m$, @nd
form@lly proofed $y$tem$ w!thout tr@pdoor$. The$e protocol$ $hould norm@lly refu$e to
@ccept comm@nd$ th@t could c@u$e the dev!ce to exh!b!t beh@v!or$ th@t would h@rm
the p@t!ent. Commun!c@t!on protocol$ m!ght !nclude TCP/!P protocol $t@ck$ comb!ned
w!th typ!c@l $ecur!ty technolog!e$ $uch @$ f!rew@ll$, p@cket f!lter!ng, !ntru$!on detect!
on, @nd $ecure procedure$ for flow control @nd @uthent!c@t!on (e.g., p@$$word$, b!
ometr!c$, @nd publ!c-key cryptogr@phy) to prevent ‘‘body-h@ck!ng.’’ Depend!ng on c!
rcum$t@nce$, n@norobot$ m@y need blocker$ for v!ru$e$, worm$, @nd $p@m, @nd
protocol$ l!nked to $en$or$ th@t mon!tor $tructur@l !ntegr!ty to en$ure t@mper re$!
$t@nce.

Other $ecur!ty protocol$ m@y be requ!red to @uthor!ze re@d!ng @nd wr!t!ng d@t@ !nto
per$on@l med!c@l record c@che$ !mpl@nted !n the p@t!ent’$ body— mult!ply redund@nt
c@che$ B1 mm3 !n $!ze could hold W1000 TB of f@$t-@cce$$ mech@n!c@l memory,
c@p@c!ou$ enough to $tore @ l!fet!me of det@!led med!c@l d@t@, thu$ $!mpl!fy!ng @nd
perfect!ng med!c@l recordkeep!ng wh!le m@k!ng l!fe$@v!ng d@t@ more qu!ckly @cce$$!
ble to emergency med!c@l per$onnel. $ecur!ty protocol$ mu$t $@fegu@rd not ju$t the$e !
ntern@l d@t@ $tore$, but @l$o @cce$$ to the p@t!ent’$ !mpl@nted !ntern@l commun!
c@t!on$ network @nd @ny other !n v!vo n@norobotry th@t m!ght be pre$ent. Other $ecur!
ty protocol$ enforc!ng d!g!t@l r!ght$ m@n@gement (DRM), @ud!t tr@!l$, proce$$
@ccount!ng, exp!r@t!on d@te$ @nd rel@ted $cheme$ m@y be employed on commerc!@l
$y$tem$ to enforce p@tent r!ght$. However, @ny regul@t!on$ requ!r!ng !mplement@t!on of
embedded government$pon$ored control$ or content f!lter!ng $hould be reg@rded w!th deep
$u$p!c!on.

6.Group Protocol$: Group protocol$ m@y be requ!red to control the collect!ve beh@v!or$
of l@rge popul@t!on$ of $!mult@neou$ly !nter@ct!ng !n v!vo med!c@l n@norobot$. !t !$
hoped th@t rel@t!vely $!mple !nd!v!du@l n@norobot beh@v!or$ c@n be progr@mmed
th@t w!ll g!ve r!$e to more complex de$!red group beh@v!or$. Mult!robot control @lgor!
thm$ @re @ m@jor re$e@rch f!eld tod@y w!th precedent$ !n @gor!c @lgor!thm$, $t!
gmergy, $w@rm comput!ng, @nd @gent-b@$ed $y$tem

44
 CH@PTER 8

@DV@NT@GE$ @ND D!$@DV@NT@GE$

8.1 @DV@NT@GE$ OF M!CROB!VORE$

The @dv@nt@ge$ of m!crob!vore$ @re l!ted @$ follow!ng:-

  1.More th@n m!ll!on people !n th!$ world @re @ffected by th!$ dre@ded d!$e@$e. Currently
there !$ no perm@nent v@cc!ne or med!c!ne !$ @v@!l@ble to cure the d!$e@$e. The
currently @v@!l@ble drug$ c@n !ncre@$e the p@t!ent’$ l!fe to @ few ye@r$ only, $o the !
nvent!on of th!$ n@norobot w!ll m@ke the p@t!ent$ to get r!d of the d!$e@$e.
2. @$ the n@norobot do not gener@te @ny h@rmful @ct!v!t!e$ there !$ no $!de effect. !t
oper@te$ @t $pec!f!c $!te only.
3. The !n!t!@l co$t of development !$ only h!gh but the m@nuf@ctur!ng by b@tch proce$$!
ng  reduce$ the co$t.
4. No oper@t!on f@!lure$.
5. They m@y @l$o produce cop!e$ of them$elve$ to repl@ce worn out.

8.2 D!@DV@NT@GE$ OF M!CROB!VORE$

The d!$@dv@nt@ge$ @re @$ follow!ng:-
1. The n@norobot $hould be very @ccur@te, otherw!$e h@rmful effect$ m@y occur.
2.The !n!t!@l de$!gn co$t !$ very h!gh.
3.The de$!gn of th!$ n@norobot !$ @ very compl!c@ted one.

45
 CH@PTER 9

FUTURE $COPE OF M!CROB!VORE$

 Re$p!rocyte n@norobot$: The$e n@norobot$ would funct!on !n @ $!m!l@r w@y to

the red blood cell$ !n our bod!e$; however, they @re de$!gned to c@rry much more
oxygen th@n n@tur@l red blood cell$. Th!$ de$!gn could be very u$eful for p@t!ent$
$uffer!ng from @nem!@.
The$e re$p!rocyte n@norobot$ would cont@!n @ t@nk !n wh!ch oxygen !$ held @t @
h!gh pre$$ure, $en$or$ to determ!ne the concentr@t!on of oxygen !n the blood$tre@m,
@nd @ v@lve th@t rele@$e$ oxygen when $en$or$ determ!ne th@t @dd!t!on@l
oxygen !$ needed.
 Clottocyte n@norobot$: The$e robot$ funct!on $!m!l@rly to the pl@telet$ !n our
blood. Pl@telet$ $t!ck together !n @ wound to form @ clot, $topp!ng blood flow.
Depend!ng on the $!ze of the wound, $!gn!f!c@nt blood lo$$ c@n occur before @ clot !
$ formed.
@ $y$tem of clottocyte n@norobot$ would $tore f!ber$ unt!l they encounter wound. @t
th@t po!nt, the n@norobot$ would d!$per$e the!r f!ber$, wh!ch would then come
together to cre@te @ clot !n @ fr@ct!on of the t!me th@t pl@telet$ do.
 Cellul@r rep@!r n@norobot$: The$e l!ttle guy$ could be bu!lt to perform $urg!c@l
procedure$ more prec!$ely. By work!ng @t the cellul@r level, $uch n@norobot$ could
prevent much of the d@m@ge c@u$ed by the comp@r@t!vely clum$y $c@lpel.

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 CONCLU$!ON
Th!$ report pre$ent$ @ theoret!c@l n@norobot $c@l!ng $tudy for @rt!f!c!@l mech@n!c@l
ph@gocyte$ of m!cro$cop!c $!ze, c@lled "m!crob!vore$," who$e pr!m@ry funct!on !$ to
de$troy m!crob!olog!c@l p@thogen$ found !n the hum@n blood$tre@m u$!ng @ d!ge$t @nd
d!$ch@rge protocol.

The m!crob!vore !$ @n obl@te $phero!d@l n@nomed!c@l dev!ce me@$ur!ng 3.4 m!cron$ !n

d!@meter @long !t$ m@jor @x!$ @nd 2.00 m!cron$ !n d!@meter @long !t$ m!nor @x!$,
con$!$t!ng of 610 b!ll!on prec!$ely @rr@nged $tructur@l @tom$ !n @ gro$$ geometr!c
volume of 12.1 m!cron3. Dur!ng e@ch cycle of oper@t!on, the t@rget b@cter!um !$ bound to
the $urf@ce of the m!crob!vore v!@ $pec!e$-$pec!f!c rever$!ble b!nd!ng $!te$. Tele$cop!ng
robot!c gr@pple$ emerge from $!lo$ !n the dev!ce $urf@ce, e$t@bl!$h $ecure @nchor@ge to
the m!crobe'$ pl@$m@ membr@ne, then tr@n$port the p@thogen to the !nge$t!on port @t
the front of the dev!ce where the cell !$ !ntern@l!zed !nto @ morcell@t!on ch@mber. @fter
$uff!c!ent mech@n!c@l m!nc!ng, the morcell@ted rem@!n$ @re p!$toned !nto @ d!ge$t!on
ch@mber where @ preprogr@mmed $equence of eng!neered enzyme$ @re $ucce$$!vely !
njected @nd extr@cted, reduc!ng the morcell@te pr!m@r!ly to monore$!due @m!no @c!d$,
mononucleot!de$, glycerol, free f@tty @c!d$ @nd $!mple $ug@r$, wh!ch @re then h@rmle$
$ly d!$ch@rged !nto the env!ronment, complet!ng the cycle.

Med!c@l n@norobot$ m@y be con$tructed of d!@mondo!d n@nometer- $c@le p@rt$ @nd

$ub$y$tem$ !nclud!ng onbo@rd $en$or$, motor$, m@n!pul@tor$, power pl@nt$, @nd
molecul@r computer$. The pre$ence of onbo@rd n@nocomputer$ w!ll @llow !n v!vo med!
c@l n@norobot$ to perform numerou$ complex beh@v!or$ wh!ch mu$t be cond!t!on@lly
executed on @t le@$t @ $em!@utonomou$ b@$!$, gu!ded by rece!pt of loc@l $en$or
d@t@, con$tr@!ned by preprogr@mmed $ett!ng$, @ct!v!ty $cr!pt$, @nd event clock!ng,
@nd further l!m!ted by @ v@r!ety of $!mult@neou$ly execut!ng re@lt!me control
protocol$. $uch n@norobot$ c@nnot yet be m@nuf@ctured, but prel!m!n@ry $c@l!ng $tud!
e$ for $ever@l cl@$$e$ of med!c@l n@norobot$ !nclud!ng re$p!rocyte$, m!crob!vore$,
clottocyte$ @nd chrom@llocyte$ h@ve been publ!$hed !n the l!ter@ture.

The$e de$!gn$ @llow @n @n@ly$!$ of b@$!c comput@t!on@l t@$k$ @nd @ $umm@t!

on of m@jor comput@t!on@l control funct!on$ common to @ll complex med!c@l
n@norobot$. The$e funct!on$ !nclude the control @nd m@n@gement of pump!ng, $en$!ng,
conf!gur@t!on, energy, commun!c@t!on, n@v!g@t!on, m@n!pul@t!on, locomot!on,
comput@t!on, @nd the u$e of redund@ncy m@n@gement @nd fl@wle$$ comp@ct
$oftw@re

The dev!ce m@y con$ume up to 200 pW of cont!nuou$ power wh!le completely d!ge$t!ng
tr@pped m!crobe$ @t @ m@x!mum throughput of 2 m!cron3 of org@n!c m@ter!@l per 30-
$econd cycle.

M!crob!vore$ @re up to ~1000 t!me$ f@$ter-@ct!ng th@n e!ther n@tur@l or @nt!b!ot!c-

47
@$$!$ted b!olog!c@l ph@gocyt!c defen$e$, @nd @re ~80 t!me$ more eff!c!ent @$
ph@gocyt!c @gent$ th@n m@croph@ge$, !n term$ of volume/$ec d!ge$ted per un!t volume
of ph@gocyt!c @gent. Be$!de$ !ntr@venou$ b@cter!@l $c@veng!ng, m!crob!vore$ or
rel@ted dev!ce$ m@y @l$o be u$ed to help cle@r re$p!r@tory, ur!n@ry, or cerebro$p!n@l
b@cter!@l !nfect!on$; el!m!n@te b@cter!@l toxem!@$ @nd b!of!lm$; er@d!c@te v!r@l,
fung@l, @nd p@r@$!t!c !nfect!on$; d!$!nfect $urf@ce$, food$tuff$, or org@n!c $@mple$;
@nd help cle@n up b!oh@z@rd$ @nd tox!c chem!c@l$. M!crob!vore$ could @l$o be
u$eful for tre@t!ng !nfect!on$ of the men!nge$ or the cerebro$p!n@l flu!d (C$F) @nd re$p!
r@tory d!$e@$e$ !nvolv!ng the pre$ence of b@cter!@ !n the lung$ or $putum, @nd could
@l$o d!ge$t b@cter!@l b!of!lm$. The$e h@ndy n@norobot$ could qu!ckly r!d the blood of
nonb@cter!@l p@thogen$ $uch @$ v!ru$e$ (v!rem!@), fungu$ cell$ (fungem!@), or
p@r@$!te$ (p@r@$!tem!@). Out$!de the body, m!crob!vore der!v@t!ve$ could help cle@n
up b!oh@z@rd$, tox!c b!ochem!c@l$ or other env!ronment@l org@n!c m@ter!@l$ $p!ll$,
@$ !n b!oremed!@t!on.

  

48
 REFERENCE$
[1] Cr@nd@ll BC. N@notechnology: Molecul@r $pecul@t!on$ on Glob@l
@bund@nce. 1$t ed. M!T Pre$$; C@mbr!dge, M@$$@chu$ett$: 2018.
[2] Fre!t@$ Robert @., Jr The future of n@nof@br!c@t!on @nd molecul@r $c@le dev!ce$ !n
n@nomed!c!ne. $tud!e$ !n He@lth Technology @nd !nform@t!c$. 2017
[3]$oft M@ch!ne$: N@notechnology @nd L!fe by R!ch@rd @nthony Lew!$ Jone$

[4] Fre!t@$ Robert @., Jr Explor@tory de$!gn !n med!c@l n@notechnology: @ mech@n!c@l

@rt!f!c!@l red cell. B!otechnol B!oeng. 2017;26:411–430.
[5]Fre!t@$ Robert @., Jr M!crob!vore$. @rt!f!c!@l mech@n!c@l ph@gocyte$ u$!ng d!ge$t
@nd d!$ch@rge protocol. Zyvex. 2018:634–645. prepr!nt.
[6]Fre!t@$ Robert @., Jr Clottocyte$ @rt!f!c!@l mech@n!c@l pl@telet$. Fore$!ght
Upd@te. 2018;41:9–11.
[7] T@n!h@r@ M, N!$h!mur@ Y, $uzuk! K. @ new drug del!very $y$tem w!th controlled
rele@$e of @nt!b!ot!c only !n the pre$ence of !nfect!on. J B!omed M@ter Re$. 2017;42:112–
116.
[8] Fre!t@$ Robert @., Jr The future of n@nof@br!c@t!on @nd molecul@r $c@le dev!ce$ !n
n@nomed!c!ne. $tud!e$ !n He@lth Technology @nd !nform@t!c$. 2018;80:45–59.

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