4. lrNG Dl,ING

4.1 KMm pha, phan ph6i thu6e va cac phan tu' li~u phap4.2 Ch~n doan va di~u tr!

3.3 Cac phuonq phap sinh hoc3.3.1 Tt,J'lap rap phan tlJo3.3.2 Vi ehe tac dua tren khu6n sinh hoc3.3.3 Phong sinh hoc2.3.4 Sinh hoc phan tu'

3.2 PhU'O'ng phap vat Iy3.2.1 Cac phU'O'ng phap co hoc3.2.2 Vi dinh vi kh6ng gian3.2.3 T6ng hop trong pha khl3.2.4 H6 quang di~n

3.1 Phuonq phap h6a hoc3.1.1 Micelle ngU'Q'c3.1.2 Khu'3.1.3 T6ng hop di~n h6a

3. PHU'O'NG PHAp CH~ T~O VAT LII;U NANO

2.3 Cau true nano tich hop2.3.1 Mieroarray2.3.2 Microfluidic2.3.3 )i~n Ct,J'Cnano (nanosensor)2.3.4 Thi~t b] nano (nanodevice)

2.1 V~t li~u nano2.1.1 Dc;tngcau2.1.2 Danq thanh

2.2 Cac phan tlJosinh hoc trong CNSH nano2.2.1 Protein2.2.2 DNA2.2.3 Cac cau true khac

2. KH61 cAu TRUC vA NGUYEN LV CH~ T~O

1.2. Huonq nghi~n CLrUchlnh1.3 Tiern nang

1.1 t.ich su' phat tri~m1.1.1 C6ng ngh~ sinh hoc1.1.2 C6ng ngh~ nano1.1.3 C6ng ngh~ sinh hoc nano

MI,JC Ll,IC

1.GIOI THII;U CHUNG

Hinh 1. Cac phan tu' DNA co kich thuoc khoanq 2,5 nm. 10 nguyen tLl'H xep lien nhaudai 1nm (Theo www.cecs.ucf.edu).

To chuc Nanotechnology Initiative (NNI) true thuoc chinh phu My dlnh nghTacong nghenano (CNNN) 113 "bat cu' thu' gllien quan den cac cau true co kich thuoc nho han

1.1.2C6ngngh~ nano

Nano theo tieng Latinh (vavoa) nghTala nho xiu. Vao th~ ky thlPVII truce Cong nguyen,Mimnermus, thi gia HyL9P, da sang tac bai tho c6 ten unCI'hoang Nawo". Den the kythir II sau C6ng nguyen, vavvo 103 ten mot loai banh bo co d~u oliu, sang the ky thu' IIIsau Cong nguyen thi no I~i mang nghTabon nia bat dia ton.Tien to nano xuat hien trong tal li$u khoa hoc Ian dau tien vao narn 1908, khi LohmannSlYdl,mgn6 de chi cac sinh v~t rat nho v&i dLPangkinh 200 nm [3]. Vao narn 1974,Tanigushi Ian dau lien SLrdl,mgthu~t ngli conq nghe nano (nanotechnology) ham if Sl,Ylien ket cac vat lieu cho kY thu~t chinh xac trong tu'O'nglai [3]. Hien tal trong khoa hoc,tien to nano bieu thi con 56 10-9 nrc kich thuoc 1 ph~n tY m (hlnh 1).

1.1 Llch 5U'philttri~n1.1.1Cdngngh~sinh hoc

C6ng ngh$ sinh hoc (CNSH) thuc Sl,Y tra thanh mOtnqanh cong nghi$p vao cu6i nhCmgnarn 1970 nhunq n6 da dU'Q'Cde cap va lien dean tiem nang pnat trien tv 60 narn trLP&Cd6 [1]. CNSH la tap h9'Pcac kham pha khoa hoc va ky thuat thl nghiem cho pnep cacnha khoa hoc thao tac va su' dl,mgcac h$ th6ng sinh hoc trong nghimClPUco ban vaphat trlen cac san pharn thuonq mal [2]. V&i nelntang la eong ngh$ tal to h9'P,CNSHda va dang c6 nhl}ng buoc tien than kY, v6'i nqay canq nhieu lPngdt,mgmoi.

CNSH hi$n dai tap trung nghien ciru cac qua trinh, co chi! (:y rnuc phan tCY. Sinh hocphan tu' canq phat trien, cang can cac cong cu, vat lieu m&i nnarn tham nh~p sau hanvao th~ gi&i hien vi cua nhCmgqua trinh, diu true sinh hoc.

TAl LI~U THAM KHAo

1. GIOI THII;U CHUNG

4.3 Khang vi sinh vat4.4 PMt hi$n-xac dlnh cau tLr sinh hoc4.5 PMn tach cac cau tLr sinh hoc4.6 May tinh nano sinh hoc

1.1.3 Cong ngh~ sinh hoc nano

CNNN phat trien ttH yeu dan toi nhu cau tim kiem cac m6i lien ket giCYanhCYngvat cokich thuoc nano. 8i~u do tl,l'phat dan t&i sinh hoc (ITnhvue khoa hoc "nang" nhlt)(hinh2). Cac nha khoa hoc mong muon SI)' giao thoa giCYaCNSH va CNNN b&i Ie CNNNmang lai cho sinh hoc nhCYngc6ng Cl,J l1'l&itrong khi sinh hoc cho phep CNNN dat duoccac h~ th5ng co chuc nang moi [7]. Cong ngh~ nay tao ra Sl)' hop tac chua tung cogi(fa cac nha khoa hoc v~t li~u, v~t Iy hoc va sinh hoc [8]. CNSH nano Iii t~p con cuaCNNN, n6 cOnggan vai CNSH nhU'ngthem kha nang thiet ke va bien dOicac chi tiet

Hlnh 2. Moi tu'O'ngquan giCYacac thist b] may mac (dong ho) co klch thuoc urn den mmva cau tv sinh hoc (ribosom, tien mao) co kich thuoc nano [Theo 5].

CI,Jthe hon, CNNN ta khoa hoc, ky thuat va thao thac lien quan toi cac h~ th6ng co kichthuoc nano, tY do cac h~ thong nay thuc hH;lnnhiern VI,Jdi~n, co, sinh, h6a hoac tinhtoan d~c bi~t. N~n tang cua cong ngh~ nay Ia hi~n tU'Q'ng"cac du true, thiet b] va h~thong co tinh ch~t va chLPCnang mol khi a kich thuoc sieu nho". C~u true co ban cuaCNNN baa gam cac hat hay tinh the nano, lop nano va ong nano. Cac cau true nanonay khac nhau (y cho chunq dU'Q'ctao thanh nho the nao va cac nguyen tLr, phan tl) cuachung duoc siflp x~P ra sao [6]

Trong cuon "Bionanotechnology: lessons from nature", Goodsell dlnh nghTaCNNN la"thao tac va che tao tY quy mo nano voi do chinh xac nguyen hi" [5].

1OOnm". Dinh nghTa nay da loai bo mot each doc doan chu the cua cac nghien cuu lienquan khac t~p trung vim cac thi~t bi vi long (microfluidic) va cac vat lieu dang dU'Q'cti~nhanh & quy mo I-lm [4].

Chup anh va nghiemcou tLl'O'ngtac giO>acac don phan tLl'sinh hoc, Mang chuc nang tV' lap rap vai cac tinh chat nhU'xuc tac, quang hoat, dlm di$n, di$nhoa va IQCnuoc, loc khl, vi sinh vat. Dong co DNA (DNA motor) dl)'a tren h/C tao ra khi lai cac trinh tl)I b6 sung vai nhau. Chup anh qua trlnh van dn~ ella virus, protein, prion va thu6c trong te bao s6ng. Chuyen gene va dt bien diem chinh xac. Cac bQ phan phan tLl'mai hU'ang dreh va tang phan ling miemdjeh Cong nghe phan ph6i thu6e hu'ang dich Khai thac cac dong co sinh hQCnhu co va cac protein van dong khac, de tao nang11I'Q'ngdien hcac CO'.

1.2.HLPang nghien CLPU chinhCung voi SI! no ro cua CNNN, CNSH nano cOngdang co nho>ngbuoc tiElnthanh kYoMot s6 vi du cua CNSH nano trong nghien cou va phat triiln [11]:

lrNGDVNGHlnh 3. BCYctranh toan canh CNSH nano. Trong do, cac h~ thong, thist bi rieng Ie cOngnhu tich hop duoc tao ra ttl n~n tang la su giao thoa giO>aCNSH va CNNN nharn CYngdl,mg trong y hoc, sinh hoc... (Theo www.nan02Iife.org)

Ph;m phO. 'huoeChua" cJo.1n

Kh3m pha fhuoePh3t hltn gl3m S3t

a day, din phan biet giO>a'Nanozfsto' (SLPdl,lngCNNN d~ phan tlch va tao ra cac h~thong sinh hoc), va 'Bi02Nano' (su dunq vat li~u va cau true sinh hoc de tao cac h~th6ng ky thuat) [10]. Hlnh 3 the hi~n khal quat cac dinh nghia CNSH nano neu tren.

Theo NIH. CNSH nano la: 1. Ap dunq cong cu & kich thuoc nano vao h~ thong sinh hocva 2. SLi'dl)ng h~ th6ng sinh hoc lam khuon mau dll phat triiln cac san pharn m&i c&nano.

sinh hoc & moe dO nguyen t& [5]. Hien co nhieu each dinh nghTa CNSH nano.

CNSH nano la bt cCY ll'ng dunq nao cua CNNN trong nghimcuu sinh hoc bao gbm:kharn pha thuoc, thi~t b] phan ph6i thu6c, cong Cl,lchuan doan, li~u phap va v~t Ii~usinh hoc mai [9].

(' ong ngb.~ Cong ty N~n tfulgPlmn tich sinh h9CSPM Hitachi High Technologies (UK) Electron-beam lithography"

Imago SClentific Instruments (WI) Leap atom probe microscope"Veeco (NY) Near-field scanning optical microscope"

Mang Affymetrix eCA) Mang oligonucleotide m~t d9 cao"(array) BioForce Nanosciences OA) Nano array"

Nanogen (CA) Mang oligonucleonde v6'ld~c tnmg phan C1,It"Nanolnk (IL) H~ th6ng in thach ban nano dip-pen*

f)u6i phan til' Dendrinc Nanotechnologies (MI) Dendruner"(Molecular Evident Technologies (FL) Tinh th~ QD ban d'nAtag) Genicon Sciences (CA) Microarray, thi~t bi ch\IPanh va phat hi~n

NanoPlex (CA) Nano-bar-codes particle kit*Nanosphere (IL) H~ th6ng va m~u dOh9t vang nanoQuantum Dot (CA) V~t lieu g~ QD (streptavu:iin,biotin .. ) ..

Microfluidic Caliper Technologies eCA) Micro[luidic"Fluidigm (CA) Multilayer soft lithography microfluidicNanoweam (CA) Sang IQchi~u nang caoSurface Logix (MA) Sang lee hl~u nang cao sti' dung thach ban tllIIl

va tinh cht h6a hQCbe m~t SInh hQCPhan p)uii tlU18c,,-:\liju phapLi~u phap Alnis Biosciences (CA) Hat nano da chirc nAng

ALZA (Mountain View, CA) Hat nano lipid phil polyethylene glycol; Doxil=NanoCrystal Technologies (PA) Cdng ngh~ NanoMill dS tao tinh th~ nanoNanoMed Pharmaceuticals (M!) Ch tic khuOnnano cho cac he th6ng phan ph6i

vaccine va thu6cAlms Biosciences (CA) Hat nano cia chirc nang.. . . . ... . .

Hien tal tren thi tnronq da co nhLi'ng san pharn thuonq mal ella CNSH nano. Bang 1 Ii~tke mot s6 conq ty thanh conq trong ITnhVI,I'CCNSH nano theo ba hLl'ang nghien cuuchfnh la (i) phan tich sinh hoc; (ii) phan phoi thu6c va li~u phap; (iii) thi~t b] y hQCvacam bi~n sinh hoc. R6 rang, c6 st)' ch6ng Iflp giO'acac linh Vl)'Cnay, va mQtlinh Vl)'Cphat tri~n se xuc tac Sl)'phat tri~n cua ITnhvue kMc [12]. Nhu' mot tt y~u trong cac ITnhVt)'C eong ngh~ cao va mol. My luon la nuoc dan dau the hien 0 so cong ty VLI'ot trQi.Tuy nhien, mot so nuoc khac nhu Uc Nhat, Canada, Nh$t, Anh cOngda co nhLi'ngconqty tham gia vao th] tmong day ti~m nang nay.

Bang 1.Cac cong ty thanh cong trong linh vue CNSH nano [12].

Du'qc toan th~ gi&i nghi~n cuu va dau tU!phat tri~n, ngan sach dau tu cho CNNN cuacac t6 chuc thuoc chfnh phu da tang khoanq 7 Ian t(J'430 trieu narn 1997 len 3 f USDnarn 2003[13]. Ty 1$dau tu cho nqhlen cuu va dao tao CNSH nann bang khoanq 6%cua cong ngh$ nano. Trong ITnhVI,I'C tlJ'nhan, cac conq ty Ian hi~n 1~ptrung CrngdunqCNNN cho vat li~u, h6a hoc, di~n; d~u tU' trong dU'Q'Cva cac h~ th6ng sinh hoc nannkhac Ll'OCtinh khoang 10%. Tuy nhien, cac cong ty nho va quy dau tLl'mao hi~m chinhi~u han trong ITnhvvc nay (30-40%) [13]. Tu' narn 1999,52% trong 56 900 tneu USDtrong quy dau tu mao hi~m chi cho CNNN t~p trung van thi~t I~p CNSH nann (hlnh 4a).Tren thuc te, trong khi trong khi von dau tu mao hiem suy giam t(J'nam 2001 den 2002,d~u tLl'van CNSH nano I~i tang 313% (hinh 4b). SI)' tang trU'o-ngnay do hai yeu to chuchot: cac U'Udai cLiachfnh phLiva 51,1' khan hiem cae sang che y dLl'Q'chQC[9]. Tren50% v6n dau tU'mGlOhiem trong 4 nam g~n day dlJ'Q'Cchi cho cac cong ty hOGitdongtrong CNSH nann [8].

C6 the n6i, trong thai diem hien tai, c6 the thay tiem nang phat trien cua mot cong ngh$hay kY thuat rnoi ra nhat qua nguon nqan sach nghien cuu hang narn va doanh thu demlai tLl'cac san phftm thuonq rnai cua n6.

1.3Tiem nang

"': 1)5rhuong mal hoa

Alnis Biosciences eCA) Hat nano da chirc mngStarPhanna (Australia) Dendrimer VivaGel khang HJV (pha J)

phan ph6i Advectus Life Sciences (Canada) H~ thNTCure, v~ chuyen thu6c ch6ng ung thirthu6e qua hang rao mau nao

BioDelivery Sciences (NJ) Cu true nano tru xoful BioOral til'16'plipid kepCAP dE phan phfu thu6e (pha I)

BioSante Pharmaceuticals (I I.,) Phan ph6i thu6c dUngfullereneC-Socty (TX) Y~u t6 hucng dich gay hoai t\t kh6i u gfulVO'l

cac tinh th~ keo cua vang; vector trong li~u phapgene.

Cytlmmune Sciences (MD) Hat micell nano NanoCap dung cho thu6c kh6ngtan trong runrc (dang phat tri~n)

NanoCarrier (Japan) Nhu tuong nano khang khu.n(pha II)NanoBio (MI) Nanoshell dung eho li~u phap quangNanoSpectra Biosciences (Texas) Hat cu nsno dUngtrong y hoc ho~c cac yeu t6Targesome (CA) chuckdoan

TIti.~tbi y ~ChS tac mo AngstroMedica (MA) KhuOnxirong hydroxyapatite nano nhan tao

NanoMateria (lL) V~t lieunano dung cho tun, SI,In, va ph\lc h6lthn kinh

pSiMedlca (UK) BloSilicon c~y trong zuongf)i~n eve sinh Agilent eCA) Giai trlnh tu 16nanoh9C 454 Life Sciences (CT) f)ia giai trlnh Il,t PicoTiter

US Genomics (MA) Gifutrlnh tu mach don DNANanomix (CA) f)ien eve sinh hoc NT

Khu cong ngh~ cao TPHCM cOng tap trung d~ymanh CNNN [21]. Trong tri~n khai thvctien, thanh cong rl,.l'Crcynhat cua CNNN tHBK - TP.HCM [18], TrLl'ongf>H-KHTN [19] va El~i hoc Cong ngh~ trvc thuoc ElHQG-HN [20], f>HBK-HN Ciava dangnqhien Cl1U,dao tao v~ cong ngh~ nano.

Theo National Science Foundation, thi trLl'ongCNSH nano se dat xap XI 36 ty USD vaonarn 2006 [15].

Nuac Ngan snell (ti i~u $mam trir c ac ti uimg hop chi rilFng)Ja9.M $810 (2003)US $774 (2003)European Union $1 2 ty/4 nsmGermany $118 (2003)V.nit.~d.KiogqQm $90 (2003)frn!)'G.~ $50 (2003)A,",m:~liil $93 (2003)K9r~a $1.2 ty 110 namr~.w!l.n $110/6 namChina $280Swi~z.erland $45/3 nam.Ga.na4a $80/5 rWn

M~c du My chiern g~n 1/3 t6ng chi cho CNNN toan cau [9]. Cac quoc gia khac clingkhong Clungnqoai cuoc, sau 3 narn k~ tl) khi CI,I'Utong thOngMy Bill Clinton thanh I~pNNI, 35 qu6c gia khac CI~xay dl,mg cac chuonq trlnh trong cOngngM nay [8]. N~m2004, chinh phu My chi 847 trieu USD cho CNNN trong khi d6 Nh~t va lien minh CMuAu cling chi khong kem. Thai Lan dang (y giai doan giCraella chuonq trinh CNNN quocgia 6 narn v&i tong nqan sach 620 tri~u USD [14]. Anh la quOcgia cuai cung tang chitieu trong cong ngh~ nano, ClLI'Q'Cgi&i thi~u vao thang 6 mot Sl,.l'g~n nhLl'gc1pdoi camk~t cua n6 voi 90 ($141) tri~u cho quy MicroNanoTechnology Network [8]. Ngfm sachdfiu tu' cho CNNN cua chlnh phOmt s6 ruroc duoc th~ hi~n trong bang 2.

Bang 1. Ngan sach chinh phu d~u b.r cho CNNN tren th~ gioi [8).

19992001

fO+-----~----~--~---- ,020021Hlnh 4. Su'c cam d6 ngay canq t~ng cua CNNN vai cac nha Clfiutu. (a) VOnClfiutu maohi~m chi cho CNSH nano so VCYicac ITnhvue CNNN khac. (b) Quy ClfiutlJ'mao hi~mhang narn chi cho CNNN [Theo 9].

Lo~ DII~ kmh (ll1lI)NguytDtU H 0.1Fullerene IDNA 2Ongnano 330Protem 550QD 210Den

QD 113m(>that vat chat oU'Q'Ctita chia v~t li~u nano thanh:

V~t li~u nano khong chieu (ca ba chieu d~u co kich thuoc nano), vi du, dam nano,hat nano...

V~t li$u nano met chieu la vat Ii~u trong d6 hai chieu c6 kich thuoc nano, vi du, daynano, ong nano (NT),...

V~t li~u nana hai chieu la vc;.tli~u trang do m9t ehieu co kfeh thuoc nana, vi du,rnanq mong.... Ngoai ra con c6 vat li~u c6 cau true nana hay nanacomposite trang d6 chi c6 motph~n ella vat li~u c6 klch thiroc nm, hoac cau true cua n6 c6 nana khong chieu, rrX>tchieu, hai chieu dan xen Ian nhau.

Phim loai v~t li~u nano

Hinh 5. Kfch tnuoc v~t li~u nana va te baa (Theo http://dvwarld.narthwestern.edu/)

rumhrongtir

I I. ttlllJ I l IUUJ I u..J """nI I I '''!fA " 11,,,4I A I nm 10 nm 100 nm I um 10 pm 100um

'T'

ff~FITe ,.-L,

GFP

v

NgI!yEn Ph~ tV Protein Hat keo Va~ Te bAotV Ihu~c nhu6m huYnh quang Vatlg d9Qg~t

La nano OU'Q'ctao nan tLYcac v$t li~u ran (nhu' silicon nitride) b~lng ky thuat khac boi tiaion (ion-beam sculpting technique) [32, 33] theo hai each: tao 10bi3ng each khilc trenmang, noac lap cac 10Ian non dU'eYinhO'ng di~u ki~n a d6 qua trlnh chuyen kh6i bien tachu dao. Chieu sau cua 10nano tren mang la 5-10 nm va oLl'cmg kinh 1018 3nm. Chungnho den mlfc chi cho mot mach don DNA oi qua (hinh 8a).

Lo neno (nanopore)

BO'n vi nhanh: CIO'nvi nhanh ben trong c6 the toan bQ la amin (DAB-Am = PPI =Astromol), han hop amine/amide (PAMAM), toan b('>amide (L-Iysine dendrimers),gallate hoac resorcinolate. Neu muon dung dendrimer lam thuoc, can dung don vinhanh phu hO'Pvoi cac (J.>ngdunq duoc hoc (kh6ng oc, hieu qua cao, co kha nanggiam sat.. ..).

The lien ket va b~ ~t: Tinh CIad~ng cua cac diu true dendrimer OllQ'Ctao nen chu yeunhat bai nh6m b~ mi\'itva loal the Ii~n kat dU'C)'cdung [31].

Chat kho'i mao (initiator): C6 the tao dendrimer tLYphan tll' gOc 18nguyen to da trio Cothe gan them cac nhorn chuc oe tao dendrimer oa chuc nang.

Hinh 7. Cau true hai va ba chieu cua dendrimer. Ba thanh phan cau true: 16i (vanq),vung ben trong chua cac CIO'nvi nnanh I~p lai (xanh da troi) va b~ mat ngoai (CIo) [Theo12].

Dendrimer la cac phan tLr OllQ'Cche tao b~ng each them lien tiep cac don vi nhanh toara ngoai tu' CIiem khai CIau (hlnh 7) [31].

Dendrimer

Trong so cac v~t Ii~u nano, QD hi~n oLl'qc nghien CLrUva Lrng dl,mg nhi!u nhat. C6 thenoi, vO'i nhl1ng U'Uoiem vuot trQi cua mlnh, QD se dan thay the cac chat phat huynhQuang trong nhO'ng ll'ng dunq tnroc ofly nhu lai in situ, FRET, xac dinh kha nang dioong cua te bao ....

Hlnh 6. Vi hat g~n vai QD mang lai rnau khac nhau cac phan tLr sinh hOC.MU'ai rnaukhac nhau phat ra tLYQD (CdSe gtm voi ZnS) dLl'ai tia UV [Theo 30).

Ngoai NT carbon, cung v&i Sl! pbat trien cua cong ngh$ nano, ngay nay ngU'ai ta contao ra NT peptide [45].

Co the gan cac cau hi sinh hOCvoi NT carbon (hinh 9.3), cho phep SLYdunq h$ thonglai nhu cac thiet b] cam bien sinh hoc hoac transistor vai ph6 hoat dong r~t hi$u qua.tao ra cac cau true nano phuc hop va mach nano (nanocircuit) vai cac tinh chat vacnuc nang du',cdieu khien [44].

2.1.2D~ng thanh

6ng neno

DU'Q'ckharn pha Ian dau tien boi Dr. Sumio Lijima 1

Ma vach nano dU'Q'chieu la v~t li~u nano c6 kha nang rna h6a khac nhau tU'ang (J'ngvoi tung toal phan tLYdlch. Chung c6 the la cac hat nano hlnh nu c6 vach phan bo tt,l'do, rong 12 - 15 urnva dai 1 - 50 prn, Cac m6 hinh soc lam chung tach biet (giong nhuma vach truyemthong) dU'ai anh sang, kinh hien vi huynh Quang hoac khoi pho (hinh11) [29]. Nanobarcode tao thanh vua c6 kha nang ma h6a vua c6 kha nang do.

Mii veer: nano (Nanobarcode, NBC)

2.(1)0Hlnh 10. Cau true soi vang trln lc5iactin [Thea 54]. Day nano qufm quanh soi t6c (Theohttp://planet.tvi.edu/).

Daynano

Cac day nano kim loai khac nhau gem bac [46], vang [47], platinum [481,palladium [49],ZnS [50], dong [51], silicon 152]ducc tao ra nho khuon DNA hoac tong hop h6a h9C.C6 the tao sqi vanq nano bang each SLY dl,lng protein dan hLP&ng(RecA) [53]. Patolskyve cng SI,l' polymer tLrng buoc cac don vi monomer G-actin g~n hat vang nano va cacdon vi G-actin kh6ng danh d~u de tao ra cac sot protein g~n kim loai sau khi xuc tac Sl,!'kim loai h6a cac hat nano (hlnh 10a) [54]. Hlnh 10b minh hoa day nano silica quanquanh mot sgi t6e, n6 nho bang mot phan nam virus, nhLl'ngben gap 5 Ian to' nhen.

Hlnh 9. NT carbon nguyen chat va g{m vol cac cau t(J'sinh hQC.(1) NT carbon 1 vach,(2) nhieu vach (Thea http://dvworld.northwestern.edu/).(3) Ong nano carbon gan voicac cau tLYkhac nhau: a) gan nucleotide; b) gan oLl'ang; c) gan chat hoat oong be mat:d) gan peptide; e) g~n CSO. [Theo 441

2.2 Cac phan tv-sinh h9C trong CNSH nanoT~ bao la t$p hop cua hang ngan b may nano (nanomachine, nanodevice), chunq cothe duoc thu nh~n va bien d6i de thuc hi~n cac nhlern vu CNNN tLlYtheo chu djnh cuachung taoHi~n tQi,tr~n 10.000 be;>may nanDdang lam vi~c trong cO'the mOingU'CYi.

Ngoai nhO'ngvat li~u nano ke tren, vai cac phu'onq phap t6ng hop h6a hQC,ngLPCYitacon tao ra cac diU true

F1.....TPh4r

De)ngCCi sinh hoc nano la protein va phLYCh$ protein thuc hi(m cac chtrc nang khacnhau thiet yeu cho Sl)'song nhu tai ban va bi~t hoa cua te baa. Chung stYdl,Jngnang1U'Q'ngh6a hoc, di~n h6a hoac di~n the va chuy~n nang 1U'Q'ngnay thanh ll,YcCCi hoc[63]. TI,J'nhien luon cung cap cho chung ta mot dai rong cac dong coosinh hoc nano(hinh 13), chunq du'Q'ctien h6a d~ thuc hi~mcac chLYCnang d~c biet vai hi~u qua cao[64]. Cac protein van dong nhu myosin va kinesin dong vai tro van chuyen va truyende)ng,cac de)ngco' co ban chat RNA lam virus de dang bao goi axit nucleic [65], RNApolymerase chuyen dong doc theo DNA khi phien rna, [66] va d(>ngco tien mao day vikhufln di [67]. Mt s6 enzyme nhu kinesin, RNA polymerase, myosin, va adenosinetriphosphate (ATP) synthase co chuc nang nhU'cac dong coosinh hoc quay hoac tinhtien a klch thu'()'cnano.

Trong CNSH nano, protein duoc SLYdunq refitph6 bien. Chung c6 th~ dong vai tro maudo trong ky thuat protein chip [62], tro giup qua trlnh tl,YI~p rap theo CCi che khanqnquyen-khanq th~ [38], dLYQ'cbao goi trong cac v~t li~u nana khac nhu mot phan tLYli~uphap (khang th~) [38] va d~c biet nh~t 113vai tro dong co nano.

2.3.1 Protein

Theo xu the hien nay, nglfoi ta khOngnglmg tim hieu, kharn pha cac co che sinh hOC.tan dunq toi da moi tiam nang san c6 trong cac h~ thong sinh hoc d~ LYngdunq vaoCNSH nano. Bai the, co th~ noi rnoi cau tLPsinh hOCdau da va dang 121doi toonqnghien CLYUcua CNSH nano.

Dang chu y la sau khi tach va tinh che, cac be)may nano nay van gill' chuc nang (y kichthLYOCphan tLY.Chung la nhCrngbe)may phan tLPd

Ngay nay, ngu'()'i ta thi~t ke va che t;;to cac bo may sinh hoc nanG de thl,J'Chi$n cacnhiem vl,l di;3cbi$t (y quy ma nano, nhu' hLl'ang dich tai cac te bao ung thlf hoi;3cgiaiquyet mot mot nhi~m vI,! may tinh dan gian. Khi CNSH nanG phat trien, chung ta S9 taithist ke cac bo may ph~m tLYclIa te bao de thl,l'c hi~n nhCl'ng nhi~m cong ngh~ va slickhoe con ngLl'oi (y quy ma Ian han. Cac dIU truc Ian S9 dLl'Q'cxay dl,l'ng voi do chinhxac nguyen ttl vai cac may lap gMp phan ttl sinh hcho~c b~ng cach Stl dl,mg cac mahlnh sinh hOCde I~p ghep. Nhin VaG te bao, chung ta c6 th~ tim thay cac dong Co' tt)'

Ngoai protein va DNA, mt so cau truc sinh hoc khac cOng cho thay tiem nang Lrngdl,lng to lo'n trong CNSH nano. Cac lap be m~t te bao vi khuan gQi la S-Iayer. S-Iayerneoglycoprotein lich hQ'p c6 the SLY dl,lng trong thiet ke vaccine, phan phoi thuoc SLYdl,lng SI,I'nhi;ln biet carbohydrate. Ngoai ra, co the SLYdl,lng glycoprotein, polysaccharide,mono hay oligosaccharide lam mau do trong glycan array [74] ho~c chinh ban than tebao cOng dU'()'c lQ'idl,lng lam khuon de che t;;to day nanG [50]. Vai st)' phat trien nhu'vObao cua cong nghe hi$n nay, co the noi, l1lQicau tLYsinh hQc a kich thLl'ac nanG deu coti~m nang Lrng dl,lng trong CNSH nano.

2.3 Cau true nana tieh h9'P

2.3.3 Cae eau true khae

Mot rnanq ung dunq rat Ian noa cua DNA la lam mau do trong gene chip, mot ky thuatchi t'T1&idLFQ'Cphat minh VaG dau nhQ:ng narn 1990 va tiem nang phat trien co the so vaipeR [62]. Ngoai ra, vai cac tlnh chat tl,l' lap rap (TLR), bat cap bo sung ... , voi kha nangtOng hop nhan tao chlnh xac phan tll' DNA den tlmg base (ca mach don I~n mach kep),khi g~n DNA voi cac diu tll' sinh hOChoac cau true, phan tu' nano khac se cho ta nhO'ngung dl,lng het SLrCphong phu va da danq. Co the noi, CNSH nano m6'i chi loi dl,lngduoc mot phan rat nho be so voi ti~m nang von co clla DNA.

Co the stYdunq tinh chat nhan biet phan tLFket hop vol cac tinh chat co hoc khac nhaucua DNA mach dan va kep de tao cac thiet b] nano thuc hi(m nhieu nhiern vu han vaicac ling dunq by che t90 nano den phan phoi thuoc thong minh [71]. C6 the dung DNAde tao ra cac bo may vai kha nang chuyen dong quay, d~y va gian dai, hoac th~m chivan dong dc\ng hU'6'ng [71-73]. Co the phat minh cac thiet b] nano tt)' sinh de b~t giCf vagiai phonq cac phan tu', thuc hi$n cac nhiern vu xu' Iy thong tin don gian [71].

Ket hop cac dong co phan ttY sinh hoc voi cac h$ th6ng dll'Q'c che tao (y kich thuocnano cho phep phat trien cac thiet b] lai ho>uco-ve Co' co kha nang stY dl,mg ATP nhungu6n nang ILFQ'ng.Cach tiep can nay c6 the cho phep tao ra cac cam bien, bien nangCo' hoc va Co' cau truyen dong t'T1&i[68, 69]. Cac Co' che bai d6 cac dong Co' sinh hoctao ra Il,I'c la mot linh vue nghien cuu thu vi trong d6 cac qua trlnh dang ke dlfQ'C taothanh [70]

2.3.2 DNAC6 the n6i, chua mt cau tLYsinh hoc nao dLl'Q'cnghien cuu ky nhu DNA. Tuy nhien, c6Ie khOng ai c6 the ngo rang DNA l

2.2.3 );~neve nana (nanosensor)

Hinh 15. Anh M thong nanofluidic thuc hi~n 3 qua trinh song song dong thai stYdvngcac the tlch mau 1,6 nl, 1,0 nl va 0,4 nl de tach DNA [Theo 81].

Mt so thiEtbi di~u khian lQ'idl,mgU'Uthe cua cac thiet b] kich thuoc nho (cO'IJm)so voicac thi~t bi Ian: giam lu'oongmau va h6a ch~t tieu ton, thai gian phan tlch ng~n han, dOnhay cao hon, mang lai cac phan tlch in situ thoigian thuc va tien loi. C6 the hinh dungla tU'o'ngtt)' vai cac vi mach tich hop SlY dl,mgtransitor thu nho trong tinh toan tt)' dong,microfluidic chip c6 the dU'ooctt)' dong h6a quy mo Ian trong qua trinh sinh hoc stYdl,lngcac the tlch nl. Ngay nay, chunq ta dang thay cac h~ thong microfluidic th~t Sl,l' noi lende di~u khien cac vat li~u a moe nl, chUng dU'Q'cgOila cac h~ thong nanofluidic [81].

2.2.2 Microfluidic

Hlnh 14. Mot so loai microarray dian hinh. (A) DNA array [Theo 62]. (8) Nanowire array[Theo 54]. (C) Cantilever array [Theo 80]. (D) Protein array [Theo 77].

2.2.1 Mlcroarray

Trong kY thuat DNA array, ngU'oi ta co djnh axit nucleic c6 trinh tt)' xac dinh (mau do)tran gia the (rnanq) thich hop theo thtYb!. Axit nucleic can nqhien cuu (dich) duoc danhd~u sau d6 lai voi mau do tren mango(y nhl}ng di~u ki~n Iy tU'ang, cac axit nucleic c6trinh tt)' b6 sung S9 b~t cap chinh xac voi nhau. HO'nnoa dlfai cac di~u ki~n nay,cU'cYngdo phat hi~n tin hieu ty Ie true ti~p vai lu'oongm~u do nan c6 th~ dinh lu'oongcacloai axit nucleic trong mau ban dJu[75]. Tren co sa DNA array, cac mau do cac maudo c6 ban chat khac nhau da duoc phat trian de tao ra protein array [76, 77], PNA array[78], peptide array [79], glycan array [74], nanowire array [52,54], cantilever array [80]... rnang lai nhl}ng tYngdunq hi~u nang cao h~t sue da danq [62].

dong chinh xac, bO nho truy cap ngau nhien, cam bien ... tat ca chunq dsu 0' quy mophan tLY,san sang de thu nhan boi CNSH nano [5].

Thiet b] nano duoc dlnh nghTala t6 hop Iflp rap cua cac phan tu' da du'O'cthiet ke tlltruoc de thoc hien chuyen dng [86]. Hien co kha nhi~u thiet b] nano dU'Q'ctao ra nharnthuc hi~n cac chuyen dong tinh tie!n[87-89], quay [72], nang len ha xuong [90], co b6p(hinh 17) [73, 87, 91-93]. Ph6 bien nh~t 18 thiet bj nano doa tren DNA, ke do la cac thielb] dU'Q'cthiet ke d~c bi~t loi dl:Jngcac dong Co'phan tu>,c6 ban chat Iii protein [68,92]."Nhien li~u" cua cac thi~t b] nay c6 the la ATP, enzyme, cac klch thich ben ngoai ho~ctMm chi la tv dip nguyen li~u dl,J'alren cac thay d5i m6i tru:ang in vivo (nhu' pH) ho~cTLR thOngqua cac nguyen Iy bo sung.

2.2.4 Thi6t bj nano (nanodevice)

Hinh 16. Cau true cua aHL

Cac peptide vong chua mot s6 axit amin thay th~ danq 0- va L- dU'Q'CsU>dl,Jngtrongmt loai cam bi~n h6a sinh va h6a hoc rnoi do nh6m cua Bayley tai Texas A&MUniversity phat tri~n [85]. Trong do, ho dtIlt rnanp lipid kep chua mot kenh a-haernolysin(aHL, hinh 16) giO'ahai dung dich dien Cl,J'C,cho di~n the chuy~n mang khong d6i chayqua va do don$' chuyen mangoDong nay di doi vai Sl,f van chuyen cua cac ion chay quaken aHL vao 10 trung tam [85].

Mot trong cac di~n Cl)'Cnano dang duoc U'Utien phat trien hang dau la PEBBLE. Chungc6 kich thuoc 20-100nm, dLFQ'Cthiet ke d~c bi~t d~ sti dl,lng trong cac mOitrU'cYngsinhhoc [84]. Do c6 kich thuoc nh6 nen di~n Cl,J'Cnay tOi thi~u h6a cac tac hal vat 19 dOivoite bao. Han nO'ado thu6c nhuorn du'Q'cnang hoa trong chat n~n tro nen PEBBLE taora pha cam bien tach bM;ltvci t~ baa, do do tranh duoc kha nang gay nhieu h6a hoc.

Di~n cue sinh hoc la mot thi~t bj g6m thu th~ sinh hoc va mot y~u to chuyen d6i c6 khanang chuyen h6a nhCfng thong tin d~c bi~t thanh cac hi~u (J'ng c6 th~ do dac (nhu' tinhi~u di~n). VI tinh d~c hi~u cao cua cac thu th~ sinh hOC(DNA, khanq th~), so vai di~nCl,J'Ch6a hoc, di~n Cl,J'Csinh hoc nhay han nhi~u trong cac danh gia sinh hoc [82]. Dungvat li~u nano trong di~n cue sinh hoc cho phep sl) dt,mgmot so kY ihuat truyen tin hieurnoi. Vi m, cac di~n cue nano, mau do nano va cac M thong khac ta nhCfngllkfch trueocdu'ai ITnhVl)'Ceach manq hoa trong phan tich sinh hoc va hoa hoc, cho phep phan tichnhanh nhieu co chat Cling luc in vivo [83].

Mt s6 chat heat dng be ~t la cac nguyen ttYdtt,J'chat phan (l>ngcho vao dung djch. V~t li~u nano da pha (multiphase nanomaterial)kh6 tao ra han b~ng phuonq phap h6a hoc vi mOipha can cac di~u ki~n ket tua khacnhau. C6 th~ gi6'i han kfch thiroc hat b~ng each tao ra rat nhi~u vi trf hat nhan h6a(nucleation site) SLY dvng micelle ngLl'Q'c(reverse micelle). hoac bang each bao phu bem~it(capping the surface) [94].

3.1 Phll'O'ng phap h6a hQC

Hlnh 17.Mt s6 thi~t bi nano. (A) Thang may nano, di dng tC.l'ngbuoc tCrtr~n xu6ngdu'ai thong qua qua trinh khtYproton cua ba trung tam -NH2+- [Thea 90]. (8) Chuyend9n9 tinh lien nho enzyme [Theo 87). (C) Chuylm d9n9 tinh tien nho phan lmg lai[Theo 89].

3. PHU'O'NG PHAp CHE T~O V~T LlE;UNANO

..IIM!"

~-H'

\.,\

cB

Cac hat nano dU'Q'Cket tua thu:ang la oxit hoac hydroxid. Neu can hat nano kim loai, c6th~ khLl'oxid hoac hydroxid b~ng hydro a nhi~t d cao. COngc6 th~ khl} b~ng ruou dachuc (nhu ethylene glycol) (] nhiet dOcao [94]. Qua trinh khLi'hoa hoc rnuol kim loai(hinh 18) khi co chat on dinh de tQOhat keo kim 10Qihoa tr] khong (zerovalent) trongdung djch 16nghoac dung m6i hfru co du:Q'ccong bo Ian dau tien vao narn 1857 beYiFaraday, va each tiap can nay da tra thanh mot trong cac phuonq phap tong hop rnanhva pho bien nhat trong ITnhVI,I'C nay. Phu'O'ngphap chufm dau Mn d~ tao ra hat keo kimloai (nhu' hat vang 20nm bang each khu [AuCI4-] bflng sodium citrate) du'Q'cthiet I~pbai Turkevich [38].

3.1.2 Khu.

C6 th~ cho phan hi mO(ch~t gan cng h6a trj vai be ~t cua vat li~u) vao dung djch d~ngan can qua trlnh kat tu cua cac hat nano mai tao thanh (hlnh 18). Thiolate la cac ch~tcapping thU'ong dL1Q'cstYdunq nhat. Capping cOnghan cha ket tu [94].

i

Sroblt :-;~It'"(IM'.. ,,"II>I.)

_._DJl1l01m1Uur.d mtul (oDoid(TOllUcrocnpb)

Hlnh 18. Sl)' tao thanh cua cac hat keo kim loai co cau true nano thea phuonq phapkhl) rnuoi ("salt reduction") [Thea 38].

COUi'liOD 0(Mfr.1:\rOlD.5!;\"uslntiop

@@lUdu~tioD !l Rrca:id..tiOD

Do do, co the kat tua cac hat nano ben trong micelle. Kich thuoc hat nano bj giai hanbai kich thuoc cua micelle nquoc [94].

/I

___d;o. mcw,,~d 'I."IUIIIII Jtl . ...

1. SI)' phan ra do 6xy h6a cua di~n CI)'Canode kim loal2. Cac kim loai h6a tri n dich chuyen den cathode3. T

a bHinh 21. Thi~t bi thi nghi$m tao 6ng nann carbon dau'tien b~ng phll'O'ngphap cat b~nglaser (a), va MWNT oU'Q'ct90 ra trong cac thi nghi~m Qautien (b). [Theo 38]

C6 th~ Sll'dunq phuonq phap nghi~n tl1,JCcao ning (high-energy ball milling), con gOi labaa man co hQC(mechanical attrition) d~ giam kich thuoc vat lieu hat t(J'vai prn xu6ngcon 2-20nm. Qua trlnh nay cham va can nhieu thai gian de dat dLFOOCcac kich thuocnho nhat c6 the. U'u diem cua phuonq phap nay la tll'O'ngd6i re va de tang quy mo desan xuat 11I'oongIan vat li$u. ThOng thll'ang, de t6i da h6a nang lU'Q'ngbaa man, ngU'aita Slf dunq thep cling cao phan tli (high-mass hard-steel). An men c6 hoc cOngtao racac v~t lieu sieu 6n dinh (metastable). N~u nghi!nkhi c6 02 hoac N2, c6 th~ tao thanhoxit hoac nitrit [94).

Cat bang laze

Trong kY thuat cat b~lnglaser (Hinh 21(a ngU'oita d~t graphite trong 10va dOn~xunglaser rnanh de cat n6 trong khi tro. f)au tien, dung di~n CI,J'Ccarbon nguyen chat vai

nhiet do khi argon xung quanh 12000C. Khi mang argon tap hop cac san pharn va langchUng (deposit) khi phi) co chat lam lanh. Lap phu gem cac 6ng nann 4-24 lap (Hinh21(b, chisu dai < 300 nm, cunq vo'i mt lU'oongnho co chat nhu' onion. SWNT chi

dLFOOCtao ra sau d6, khi tron mt lU'Q'ngnho 1 wt%) kim loai xuc tac (nhu bot Co-Ni).DU'oi cac dieu ki~n tOiuu, ky thu~t nay tao ra cac day tinh the SWNT tl,l' lap rap lon, vciIu'ai tam giac x~p xl17 Ao. a quy rno lon, vlec t90 ra SWNT vai toc CIsan xuat cao

(1,5 g/h), ngu'ai ta SlY dunq laser di$n tl)' do cao nang (-200W) [38].M~c du cac no Il,I'cthanh cong trong vai narn truoc de tao ra mot lU'oongIan cac engnano b~ng cac phuonq phap nhi$t d cao & tren, van chua the SLr dl,mgphuonq phapnay quy ma cang nghiep.

Nghien true cao nang

3.2.1 Cac phU'O'ngphap co hgc

3.2 PhU'O'ng phap v~t Iy

B~ng each Slr dl,mgqua trinh t6ng hop dien h6a, c6 th~ tao ra nat diu Pd(O)v6'i klchthuoc 1 - 6 nm. Phu'O'ngphap CIienh6a CIaQU'OOcap dl)ng thanh cang CI~chuan b] mOts6 organosol va hydrosol kim lcai nhu Pd, Ni, Co, Fe, Ti, Ag, va Au & quy mo hang trammg (hieu suat >95%) [38).

Hinh 20. Tao hat nano kim loai NR4+CI-- b~ng phan tYng d~n h6a [Theo 38)

Dinh vi nho laser (LAD) 103conq Cl,Jdoc nhat v6 nhi de tao ra cac vat li$u film rnonq vada dLl'Q'Cs& dunq thanh cong de che tao cac cau true nann [95]. Ky thuat nay cho phepthuc hi$n cac I~p rap c6 thli tl)' theo 50' d6 dinh truoc biing each nang len mot each vat19 va d~c cac phan tCYI~p rap tran b~ mat ran. Ky thu~t LAD da dlJ'qc Stf dl,.lng d~ d~tglucose oxidase tren SOS, riboflavin tren phospholipid va bacteriorhodopsin nhay sang(bR) tren ch~t n!n cua lipid L-a-distearoyl phosphatidylcholine [96].

3.2.3 Tong h9'P trong pha khi

Tong hop trong khi tro la mt trong cac phuonq phap dLl'Q'cSLPdvng dau tien d~ tao v~tli$u nano. Khf tro han che nguyen tLl' khuech tan ra kh6i vung quanh co chat [94]. Conhieu each tao vat li$u nann trong khi tro. Co th~ tap hop hat nano tLi' mot vi trf trongbuang g3.2.2 Vi c1jnhvi kh6ng gian

He quang di~n la phuonq phap G;lO 6ng nana carbon d~u tien duoc cang b6 va cling 113phuonq phap san xuat (y quy ma cang nghi~p d~u tien [38).oil san xuat MWNT, SLYdl,lng hai di~n CI,I'C graphite sieu tinh sach. Khi phun ho quang di~n gHJahai di~n CI,I'Cctura vat li~u trong khl tro se lam vat li~u chuyen sang tranq thai sieu baa hoa [94].Trong qua trlnh phat trien, cac ong nano dU'Q'ctao thanh va lang tren cathode; anodexay ra qua trlnh an man lien tuc [38]. Phuonq phap nay thU'ong dU'Q'cSlPdl,lng de tao rafullerene (C60) va 6ng nano carbon. Nhi~t dOcao trong ho quang lam tMng hoa vat li~u[94].

Hlnh 22. SO'do thiet b] tao ra, t~p hQ'pva nen cac hat nano trong khi tro.

3.2.4 Ho quangdi~n

HIGH PRESSURECOMPACTION UNIT

LOW PRESSURECOMPACTION UNIT

VACUUM PUMPS---

FUNNEL

-- GAS INLET-wrEVAPORATIONSOURCES

.- MAIN VACUUMCHAMeER

ISCRAPER

3.3 Cae phU'O'ng phap sinh hoc

3.3.1 TlI'lap rap phan tiP

TI)' lap rap (TLR) ta qua trlnh tl)' t6 chuc cua 2 hay nhi~u thanh phan tnanh mot khoi Ianth6ng qua cac Ii~n ket d6ng va/hoc;.c phi d5ng h6a tr] (97). TLR phan tll' (MSA) la mC>teach tiep can tuyet vol de che tao cac cau true sieu phan tCP.MSA duoc tao thanh bc)'icac lien ket phi dong h6a tr] yeu- dang chu y la lien ket H, lien ket ion, tuo'ng tac kynuoc. van der Waals va lien ket H qua nuoc. M~c du khi dLFng rieng, cac lien ket naytuonq doi yeu nhung trong tong th~ chunq, chunq chi phOi qua trinh hinh thanh cau truecua tat ca cac dai phan tLPsinh hoc va anh hu'ang den tu'ong tac cua chung vai cacphan ttY khac, Tat ca cac phan tii sinh hoc, bao g6m peptide va protein, tuonq tac va tt,J'to chLPCthanh cac cau true xac dinh, c6 clurc nang. Bang each quan sat qua trlnh caccau true sieu phan tlY lap rap trong tt,J'nhien, chunq ta c6 the bat dau khai thac 5t,J'TLRd. tao ra nhCmg v~t li~u tong hQ'p hoan toan mai. DNA, peptide va protein la cac khOicau truc da tac dt,mg de lap rap cac v~t li~u. TI,I' nhien lu6n SlYdl,mg chung nhu cac bokhung de tGtora rat nhi~u 10

Che t~o CaGday nanDsiP dl,mgb khung sinh h9C

C6 the dung NT peptide TLR lam khuon cho qua trlnh kim lo~i h6a. Khi b khung hLruCo' bi IO

I -111111-4nm I~- .!t~GM,~"\P~h.M

Hlnh 24. Lap rap cac v~t lieu peptide. (a) Peptide tl,l'bo sung ion hoa co 16 axit amin,kich thuoc -5 nm. Chung TLR tao thanh soi nano voi cac gOckhong phan CI,I'C namtrong (xanh ta cay), va cac goc tlch di~n - (do) va + (xanh da troi) tao thanh cac tU'O'ngtac ion bOsung gi6ng nhu' ban cCi vua. Cac sol nano nay tao thanh cac chat n~n danxen sau d6 tao thanh scaffold hydrogel v&i tren 99.5% Iii nuoc, (b) Mt loai peptidegiong chat heat d(>ngbe mat, kich thuoc -2nm, TLR thanh NT hoac tui nano(nanovesicle) voi dl.l'()'ngkinh 30-50 nm. (c) Peptide bao goi nano be m~itvoi ba phandoan rieng bi~t, co the SLYdunq nhu rTlV'C de in true tiep tren ~ mat. (d) Peptide congtac phan tLP,voi tinh ILfang CI,l'Crnanh, bien doi hinh danq rnanh giCi'aa-helix va 13-strand hoac ~-sheet dU'&ikich thich nqoai lai. Cac tinh the nano c6 the du'Q'Cg~n v6'icac peptide lU'angCl)'C nay de che tao chUng thanh cac cong tac nh6 [Theo 98].

c

b

~-.5nm

..I---- (~., -,,

. . !'... ,'

2nm

Belcher va cng Sl,l'ti~n hanh mot each ti~p can r~t khac de kh6ng chi kharn pha rnacon che tao cac vat lieu dien va tLr rat khac so voi cac vat lieu truyen thong. HQ tao rabacteriophage TLR da bi~n doi di truy~n sao cho co the dung chung de chon cac v~tlieu tCr, ban dan hoac dan dien (hinh 25) [104].

Hinh 25. Kharn pha va chon cac vat li~u di~n SlYdunq h~ th

Trang tU'O'nglai, cac h~ th6ng vat li~u crurc nang dU'Q'cphat trian cho cong ngh~ sinhhoc nano hoac cong ngh~ nanDc6 the g6rn protein (hlnh 27). Chung tham gia vao quatrlnh I~p rap, ch~ tac va ch~c ch~n, trong du truc san pham cu6i cung, rnang l'ili cacchu'c n~ng d~c biet, c6 the dieu khien tlJ'O'ngtll cac c~u truc trong rna x6p va ~n sinhhoc. Trang linh VI,I'C ph6ng sinh hoc phan tti (molecular biomirnetic, MB)- trang d6 ket

3.3.3 Phong sinh hoc

Virus ki~u Virus ki~u d~t Day nano c615i lahoang dai biSn W1.lS ki~u oQt bl~n E::::=- ........ a;...iillilll

Hlnh 26. (A) So' 66 cha teo day nano tren n~n tang ky thu~t phage display va (B) daynano ZnS-virus [Theo 50].

BA

Mao va cong SI,I' da tao ra cac virus c6 kha nang ket tinh cac hat tinh the nano ZnS boacCdS bang ky thuat phage display. Cac virus nay duoc cho vao dung dich chua chatban dan va cac hat tinh the nano tao thanh doc theo khuon virus tao thanh day nano(hinh 26) [50].

Cac phan tll' DNA 8 urn, TLR trong dung djch de tao thanh cac tinh the mot mi~n c6kich thu'ac 2 x voi dOday d6ng nh~t tLr 1 den 2 nm. Han nO'a,Sl) dunq oligonucleotidetong hop mang cac base bien doi cho phep dieu khien cau true cua khoi tuan hoanbang each g~n them cac nh6m chuc nang nhu chat xuc tac, enzyme, va protein, caccum kim loai ho~c cac dIU true nano DNA khac nho polyhedra [108] ho~c vonqBorromean [50].

Nhi~u motif DNA khong thong dunq cGngco th~ duoc sUodunq d~ tao nan cac kh6i cautrue phan tUobeYikha nang ket hop cua DNA thong qua dau dinh co tinh d~c hieu r~tcao. cac phan tu' DNA phan nhanh c6 cac dau dlnh d~y hua hen cho cac cau true tuanhoan.

v~mat nguyen Iy, cac d~c trung c6 tinh I~p lai va cac motif kha nhan di~n cua cac daiphan tu' sinh hoc c6 the dlJ'Q'Ckhai thac de che tao cac cau true va thiet b] nano [106].Mt trong cac vi du tieu bi~u 103 che tao tam hoac cac day nano d~n di~n. Day nano bacdan di~n oa OlJ'Q'cche tao bang each I~p rap tren khu6n DNA [107].

3.3.2 Vi che tac dt)'a trim khu6n sinh hoc

Cac hat keo vang co the TLR thanh mot cau true tap trung b~ng each g~n voi cac hat13nm khong be sung vai cac oligonucleotide DNA co hai d~u g~n vai nh6m thiol va saudo k~t tu voi mot phuc h~ oligonucleotide voi cac dftu dinh va be sung voi hai trlnh tl,l'ghep [105]. Qua trlnh I~p rap hoan toan thuan nqhich thong qua cac chu ky lai va bientinh beYinhi~Hthong thlJ'6'ng.

Chi m(lt vai polypeptide da dU'Q'cxac dinh la gan d~c hi~u voi cac chat vo ca. Chunghau het la cac protein khoanq h6a sinh hoc, tiet ra tLl'rno ran (hard tissue) sau khi dLYQ'cphan tach, tinh che va tach dong. M~c ou each tiep can nay kho, ton thai gian va c6nhi~u giai han ton, mt so protein tach theo each nay da dU'Q'cSLYdl.,lngnhU'enzyme detong hop cac chat vo Co'nhat dinh. Cach tiep c~n pho bien hO'nla thu polypeptide ganchat ht}u cO'nha cac ky thu~t sinh hoc. Trong each tiap c~n nay, m(lt llJ'Q'nglan, thU'

Hlnh 28. Ti~m nang LYngdl.,lngella MB trong cong ngh~ nano va cong ngh~ sinh hocnano su dl.,lngcac polypeptide bien doi di truy~n gan chat vo co [Theo 38].

(Ph'n ph61thuOc)

ThilaiproteWchlt vo CCI

..J

Khoang hOe.sinh h9C

C6ng ngh, sinh h9CnIno

Glai phap thti ba la tl)' lap rap va/ho~c dong I~p rap cac phan tCrsinh hoc thanh dIU truenano co tr~t tu. 8ieu nay dam ba~ mot qua trinh lap rap tinh vi de tao ra cac cau truenano phuc tap, va c6 the la cac cau true c6 thLf bac, tuonq ll! trong tl,l'nhien.

Hinh 27. Kha nang SLYdl,mgcua cac protein gan chat vo co: (a) the lien kat de co djnhhat nano. (b) cac phan tll' ChLfCnang I~p rap tren Co'chat d~c bi$t. (c) the ket n6i danang g6m 2 protein tiep qiap voi cac dan vi vo co' nano. NSL, the ket noi khonq d~chi~u [Theo 109].

a '-------' bSubstrate

Mattrial-1

Thfr hai, c6 the SLfdunq cac protein nay lam chat kat n6i hay cac tap hop I~p rap phanttYde lien kat thuc the phan tLY,bao gam hat nano, polymer crurc nang hoac cac cautrue khac tren khuon phan tll'.

Giai phap thti nhat la chon lee la thi6t ka (y rnuc phan ttYva di truyen cac peptide,protein g~n ch~t vo ca. E)i~unay cho phep dat dlJ'qc kha nang dieu khien (y nht}ng rnothLYCnho nhat.

hop hai hoa cac Ifnh VI,J'C sinh hoc va vat Iy truyen thong- c6 the tao ra cac vat li~u laiduoc I~p rap tu.,rrurc phan tu su dunq cac tinh chflt nh~n biet va g~n d~c biet cuaprotein voi cac chat vo ca. MB mang lai ba giai phap giup di~u khien va che tac cautrue nano quy mo Ian cOng nhu lap rap cac v~t lieu hal, ba chieu mot each c6 tr~t tv(hlnh 27).

CNSH nanD phan anh tam quan trong ngay cang tang cua khoa hoc nanDva cong Cl,lnanD trong vi~c ttso tharn chi tich luy bac tai thanh te bao voi mt IlfO'ng len den25% lrong 11I'0'ngsinh khoi kha. Chung Pseudomonas stutzeri AG259, phan I~p tLr rnobac tich lOycac tinh the dan b

Hlnh 30. Nguon tai ehfnh. (a) Thong ke quy dau tLYmao hi~m tap trung trong CNSHnano tCYnarn 1998 den nay. (b) Phan be quy dau tLYmao hiem trong CNNN tCrnarn1998 t&i nay [Theo 9].

Mt trong cac khoi cau true nano duoc sU' dl,mg ph6 bi~n nh~t trong chien ILY9'Cphanphoi thuoc la dendrimer (hinh 7) b6"i tinh chat hoong dich va phat hi~n ella n6. Cac thietb] nano dung dendrimer PAMAM da chirc nang cung cap mOt nan tang nano de chup

\Malerials

12%

Devices32~NanoBlo

52%

Diagnostics37%Drug

discovery54%

bBlopharmaceuUc

Cac phu'O'ng phap hu'ang dfch khac sU' dt,mg nang IU'Q'ngngoai de ho~t h6a t~i chOhO

Gan day, Gao va c(lng sv SLYdl,Jng thanh conq aD de chup anh va hU'ang dlch ung thuin vivo. HO gan aD voi khanq the d~c hi~u te bao ung thu tien liEIlttuyen. Sau khi liemVaG chuot (da chuyen t~ bao ung thU' lien li$t tuy~n cua ngLPai), c6 the nh.;tn biet vachvp anh khang the PSMA danh dflU aD gan vai vi trl khoi u in vivo (hlnh 31) [129]. Wuva dOng Sl,l' phat trien cac rnau do aD d~c hieu va dang tin c~y de dinh vi chI thi b~ m~tte bao ung thu' vu (Her2), sO'i cytoskeleton, va khang nguyen trong t~ baa co dinh, tebaa song va phan do~n mo [131].Cong ty iMEDD (Columbus, OH, USA) ~o ra 10 nano tren cac thiel bi pMn phoi thuocdy dU'ai da de dieu khien qua trinh giai ph6ng thuoc. Cac chLl'O'ng trinh hQ'p tac giCraNational Aeronautics va Space Agency Ames Research Center (Moffet Field, CA, USA)va Stanford University (Stanford, CA, USA) dang co gan ket hOOpcac men CI,I'C16 nanoc~y vao vang mt;lc nh~m t;;lOra giao tiap chU'c nang giCra day th~n kinh va vang m;;lC(hinh 32) [12].

Thanh va Rosenzweig da phat trien m(lt thi nqhiern trong d6 nong dO khanq the dU'O'cxac dinh thong qua ham ket 11,1cua C,3c hat vanq g6i trong khanq nguyen [130]. Hirschva d6ng Sl,I'da phat trien thl nghiem ket tu de phat hi$n immunoglobin trong rnau SU>dl,mg v6 nano [36].

Hinh 31. HU'6ng dich va hi$n anh in vivo dung aD. (A) Thi nghi$m rno ex vivo cua t~bao ung thu danh dau aD trong phoi chuot. (8) Hien anh in vivo cac vi hat aD da rnautrong cbuot song. (C) Hu'cmg dlch phan to'va hi$n anh in vivo khoi u titn liet tuyen achuot dung kMng the ket hop vol aD [Theo 129].

Cac cam bien sinh hoc nano dU'O'CSLrdl,Jng thanh cong trong cac do dac n(>i bao, E>iEIlnCl,PCPEBBLE c6 th~ xac dinh pH, Mg+, CI-, K+, Ca2+, oxy va glucose ni bao kha chinhxac [84]. Cac cam bi~n nano SQ'iquang cua Vo-Dinh va cng Sl,P[127] dU'Q'cch~ taothanh cong de do nong d benzo-a-pyrenetetrol (BPT) trong bao tuO'ng cua t~ bao ungthu vu cua ngu'ai va te bao bieu mO gan chuot. f)i~n cue sinh hoc nano dung enzymede phat hiEIlngian tiep glutamate (chat truyen d~n noron quan tronq trong h~ than kinhtrung U'O'ng)mot each lien fuc da duoc che tao thanh cong, trong do thu the sinh hQClaglutamate dehydrogenase [128].

Chlm doan la linh Vl,PCdU'Q'cd~u tLPkinh phi nhi~u th(r hai sau phan phoi thuoc (hinh30). Hi~ln tal da c6 kha nhieu thanh cong.

4.2Ch~ndoim va di~utr]

Cac h$ thong trong tLfO'ng lai c6 the dLl'Q'Cl.;tp trinh truoc de c6 toe d(>phan phoi biendoi theo thai gian hoac tl! ditu hoa dap (rng vai cac klch thich rnoi tmang (nhCrng kichthich nay c6 thl phat hi~n biing cam bi~n sinh hQCtai vi tri cay). Ova tren conq ngh$kenh nano, cac h$ thong ditu khi~n hoat h6a mai dang du'O'c phat triln cho cac thi~t b]c~y ghep d~ thuc thi chu'ong trinh, di~u khi~n tu' xa va tt)' ditu h6a [117].

cac nha khoa hoc tai Northwestern University da phat trien rna vach nann (bio-barcode)sieu nhay co ban chat la hat vanq nano va DNA d~ phat hien phan tu' DNA dich (kh~mgnguyen d~c hieu ti~n li~t tuyen, PSA) (:j nang dQthap trong rnau [137]. PSA du'Q'csU'dl,mgde phat hien ung tho phei va ung thir tien li~t tuyen, hai trong s6 cac leal ung thuthU'cYngthay nhat. Cling tren nguyen Iy ma vach nano, PSA dU'Q'cphat hien thong quacac vi hat co tLYtinh nam trong kMng the don dong PSA. PSA bi bat giG'b&i vi hat co tLYtinh va phan Ling vai vo cua hat vang nann vai mQtkhanq the PSA da dong va barcodeDNA hybrid. Phtrc h~ kep PSA bi b~t giO'b(:ji tu' tinh va giai ph6ng barcode DNA. Saudo barcode DNA dU'Q'cphat hien tren mang sau khi gan v6'i cac yeu t6 gan va phat hienSlY dl,mgoligonucleotide be sung gan vo'i cac h

C6 the xac djnh trlnh tl,J'ssDNA can cli tren SI,J' van chuyen di~n tlch cua cac chuai DNAqua la nano tren rnanq silicon nitride [143] hoac qua 10 a-hemolysis tren rnanq lipid kep(hinh 34) [144]. )u'cmgkinh 10 trong ca hai tru'cmg hop cac peptide nay di se c6 kha nang di vao thanh te bao vikhuan, lam chUng bi chet nhanh ch6ng [140]. Cac nha nghien CLrUthucc McGowanInstitute for Regenerative Medicine va University of Pittsburgh d t6ng hop du'Q'ccacNT d6ng nh~t tLl>cac phan tu' rnuoi amine HBr b~c hai, NT nay c6 kha nang gist vikhuan va X8C dinh cac chat khac nhau qua chi th] mau [141].

SPL7013, mot dendrimer d~c bi~t v6'i loi h6a trj hai, voi lilu IVQ'ngthich hop trong amdao kim ham ngay I~p tuc SI,J' nhi~m HIV rna khOnggay doc [31].

4.4 Phat hi~n-xac "inh c~u tLv sinh h9C

4.3 Khimg vi sinh v~t

M6'i d~y nh~t, V80 thang 1a narn 2005, tren to Nature, Zheng ve cOngSl,l' d13c6ng bomot nghien cuu het sue thu vi. a do, ho sli dunq mang day nano silicon de phat hi~ncac protein chi th] ung thu (khang nguyen d~e hieu tien li~t tuyen) dua tren tin hieu di$nh6a voi dOnhay cao va khOngcan danh dau dich [52].

Hlnh 33. Tai tao ba chieu Pelvic Lymph Nodes dua tren anh cong hLfang tLl>dLfoi Sl,l' trogiup cua cac hat nano tu tinh [Theo 132].

Nh6m cua Lieber elitimphong trong vi~c SLPdl,JngNT carbon fullerene thanh don nhU'cac dau do trong kinh hien vi di$n til (AFM) de chl,Jpanh cac ot;li phan tlr sinh hQcnhLPkhang the, DNA, a-amyloid protofibril [155].Santra va cong SI,J' elanang h6a cac phCPch$ ruthenium trong cac lap silica mong denh~n biet te bao bGichcau [156).

McKnight va c(>ngsl,J'dachung minh SI,J' kat hop chuc nang cua cac m~u do soi nanocarbon trong te bao, Kha nang s6ng cua cac te bao sau khi g~n mau do CIu'O'cchU'ngminh bcYiSl,I'bieu hi~n dai han cua cac gene ma h6a protein phat huynh Quangxanhduoc bieu hlen chu yeu tren cac plasmid lien ket cong h6a tr] vai cac sol nano. Khi soinano va cac plasmid van lien ket, SI! dieu khien hU'ang dich va true tisp cua Sl)' bieuhi~n cua cac gene dU'Q'ckat hop dU'ang nhu la khit thi [153).

Li va cng Sl,J'da tao ra va dung nanobarcode c1~ phat hi~n DNA cua m(>ts6 10Qisinhvat gay b~nh dl,J'atren tin hi~u huynh Quangv6'i d('>nhay (attomole) va toc d('>phat hi~nrat cao [56). Cong ngh$ phat hi$n DNA da dLl'O'cChad Mirkin va dong su phat trien[154]. Dubbed 'blo-barcooe' c6 dOnhay 500 zeptomolar (zepto = 10-21) canh tranh vaiPCR. Hon nv'a, U'Udiem Ion so voi PCR la kh6ng can khuech d~i bai enzyme va c6 theap dl,mgvai protein, cOngnhU'DNA.

Xu cunq cong Sl,I'oa phat triElnmot phU'ong phap moi dua tren QD de xac dinh SNP vaihi$u nang cao [146). Dubertret va cong su da nang h6a tLPngtinh the QD trong khoiphospholipid-micell dong polymer va kst noi mixell-tinh the nay voi DNA. Sau khi tiemvao ph6i cua Xenopus, phuc h~ nay d6ng vai tro nhu m~u do phat huynh quang va laivai cac trlnh tl,J'b6 sung el~chi~u, cho phep theo d6i qua trlnh phat trien cua ph6i [147].

Maxwell cung cong Sll [148) va Dubertret cunq cong Sll (39) da khai thac tiem nang cuacac tinh the chat keo nano vang de lam tat thucc nhuorn phat huynh Quangtrong cac thinghi~m phan bi$t oligonucleotide vai chi mot base khac bi~t. Mot vi du nCPala cac maudo gan hat nano vanq ket hop voi vi chip rang lU'gc (mirocantilever) de phan bi~t motnucleotide sai khac [149] va de chuyen d6i phan tu' g~n nharn phat hi~n Sl,J'sai khac 6>rmrc urn [150]. Arun Majumdar va el6ngSl,J'elasu' dunq vi chip rang luoc CIaphat hi~nSNP trong DNA dich dai 10 nucleotide, kh6ng dm danh dau huynh Quanghoac ph6ngxt;l[151,152].

~Hinh 34. Kenh a-hemolysin oU'Q'Cthe hi~n ~t cat ngang duoc gan voi mot lap lipidkep. Khi c6 di~n ap, mach don DNA poly(dC) duoc elieukhien eliqua 10bai eli~ntrU'6'ng[Theo 145].

Hi~n t~i, may linh dung silicon da O

Mot each tisp can khac trong tinh toan tt)' dong voi DNA dua tren cac enzyme DNA(deoxyribozymes). Stojanovic va dong St)'[167] da thist ke cac cong logic khac nhaudl,l'a tren hoa.tdOngcat RNA cLiadeoxyribozyme E6 [168]. Cau truc lai DNA/RNA v6'imOtbase RNA tc;livi trf chfnh xac bi cat bai enzyme DNA khi g~n v6i cac ph~mdoa.nnh?n biet cO'chat clla chUng. Cac trlnh tt)' nh?n blat nay co the dLl'9'Cbao v~ b&i modulevong-g6c tt! lai. Bang 51,1'bat c~p base vai mQchDNA bo 5ung vO'itrinh tl,l'vong.module vong-goc co the dU'ocme)"ra. E>ieunay lam trinh tl,l'nh?n biet cO'chat kha truy

~ - .~ . -... -_._. ~.,..",.- ....

. , ..... - ~

MOtbOx& Iy micrafluidic tich hop duoc phat trien de tht,Ychi~mcac tinh toan phan t& s&dunq SNP nhu cac rna nh] phan. Mau t6ng the cua cac "giai dap" DNA danh dflu huynhquang du'Q'ctong hop crura ba base da hlnh khac nhau; da hlnh toan A hoac T du'Q'cSLPdunq de ma hoa gia tr] cua ma nh] phan (TRUE or FALSE). MOtchuonq trinh gommot chuai cac buoc bat giCr/nia/giai phonq dU'Q'cthuc hi$n va cac phan t& DNA giG'laital dau cua may tinh cung cap cho dung dich mot bai toan thong ke Boolean ba bien sobon menh dl (hlnh 35) [165].

Cac nha khoa hoc Israel voa ch~ tao ra mOtmay t1nhc6 the thuc hi~m330.000 ty pheptinh/giay, g~p 100.000 Ian toc dOcua PC nhanh nhflt hien nay. Neu nhin bang m~hthU'ang, may tinh DNA trong giong dung dich nuoc. 1.000 ty thiet b] co the nam gontrong mot giot nuoc. Cau true cua may tinh sinh hoc gom DNA dong vai tro phan rnernva enzyme giCl'vai tro phan cling. Phan (ling hoa hoc giCl'acac phan t& trong ongnghi~m cho phep nha khoa hoc thuc hi~n nhCl'ngphep tinh don giim. Nha khoa hoc raI~nh cho thi~t b] lam viec b~ng each thay d6i thanh phan phan tll' DNA. Thay vi xuathien tren man hinh, k~t qua du'Q'Cphan tich thong qua met ky thuat cho phep nha khoahoc nhan biet chieu dai cua phan t& DNA dau ra [166).

phap thay the mot, dieu do tat yeu dan toi DNA [164]. Trang khi may tinh de ban duocthi~t ke de thuc hi~n mOtphep tinh th?t nhanh thi may tinh DNA t90 ra hang ty cau traIcyicunq mQtluc. Bilu nay khien thi~t b] sinh hoc phu hop voi vi~c giai quyet cac van dllogic mo. Bien toan DNA tren the gi6'i v~n dang a giai doan so ,khai. Tuy nhien, n6 c6th~ thay doi tu'onq lai cua may tfnh, d~c bi(Hla cac t:mg dt,mgve sinh y hoc va ouochoc.

1. Bud, R. 2001. History of Biotechnology. Encyclopedia of life sciences.www.els.net:1-62. Wilson, J. 2001. Biotechnology intellectual property - bioethical issues.Encyclopedia of life sciences www.els.net:1-43. Joachim, C. 2005. To be nano or not to be nano? Nature 4:107-1094. Editorial. 2003. Why small matters. Nat. Biotech. 21: 11135. Goodsell, D. S. 2004. Bionanotechnology: lessons from nature. Hoboken, NewJersey: Wiley-Liss, Inc. 346 pp.6. Masciangioli, T., W.-X. Zhang. 2003. Environmental technologies at the nanoscale.Environ. Sci. Tech.:102A-108A7. Whitesides, G. M. 2003. The 'right' size in nanobiotechnology. Nat. Biotech.21 :1161-11658. DeFrancesco, L. 2003. Little science, big bucks. Nat. Biotechnol. 21:1127-11299. Paull, R., J.Wolfe, P. Hebert, M. Sinkula. 2003. Investing in nanotechnology. Nat.Biotech. 21:1144-114710. Grunwald, A. 2004. The case of nanobiotechnology. EMBO rep. 5:832-S3611. Moore, A. 2004. Waiter, there's a nanobot in my martini! EMBO reports 5:448-45012. Mazzola, L. 2003. Commercializing nanotechnology. Nature 21:1137-114313. Roco, M. C. 2003. Converging science and technology at the nanoscale:opportunities for education and training. Nat. Biotech. 21:1247-124914. Watanabe, M. 2003. Small world, big hopes. Nature 426:478-47915. Miller, S. E. 2003. The Convergence of N. New York Law Journal 23016. World, K. 2005. Chinh phu tap trung dau tLYcho dl)' an phat trien conq ngh~ rnoi.http://world.kbs.co.kr/vielnamese/news/news_detail.htm? No=67417. Giarn doc DHQG-HCM. 2004. Quy dinh ve quan Iy va hoat dng khoa h9Cvacong ngh~ tai DHQG-HCM. http://www.vnuhcm.edu.vn/khoahoc/quydinh/quydinh.htm18. fas.hcmut.edu. 2005. Nganh dao tao v~t Iy ky thuat.http://www.fas.hcmut.edu.vnNLKTNN/index1.html19. Chau, N. 2005. Gan ch~t cong tao nghien cuu khoa hQCva dao tao can be)tre.http://bulietin.vnu.edu.vn/btdhqghnlVietnamese/C1177/2005/03/N6842/?120. DHCN-HN. 2005. Gi&i thi~u. http://www.fotech.vnu.edu.vn/fotech_gioi_thieu.htm21. Park, S. H.-T. 2004. HOE,ltdong cua TT R&D ve cong ngh~ nano tal khu congngh~ cao TP HCM trong narn 2004.http://www.shtp.hochiminhcity.gov.vn/webshtp/tintuclcontent.aspx?cat_id=490&news id=15922. VNN. 2005. DH Bach Khoa TP He Chi Minh che tao thanh cong than nano "long".http://www.tchdkh.org.vn/ttchitiet.asp?code=104023. Dieu, M. 2005. Than nano "long" made in Viet Nam.http://nguoivienxu.vietnamnet.vn/doisongnvxlhdvktrongnuoc/2005/07/471671/24. Di~p, D. N. 2005. TLFco duyen cuoc dai den "HO'uduyen" vai cong ngh~ Nano.http://irv.moi.gov.vn/KH-CN/dndnnkh/2005/3/14209. ttvn25. Thi.d on a cyclic peptide. Nature 366:324-327A. 2005. Thiet b] do neng dOkhi gas hoa long.http://WNW.monre.gov.vn/monreNet/default.aspx?tabid=214&ltem ID=729926. Park, S. H.-T. 2005. HQ'ptac trien khai heat dng nqhien cuu cong ngh~ nano

cap de co chat bi cat. Bang each kat hop cac module dieu khien va xuc tac nay, co thetao ra cac cong logic dan gian nhu AND hoac XOR [167], may cng DNA (DNA half-adder) [169] va may tinh phan tCYco the tl,l' dng choi (va thang) tro choi "tic-tao-toe"[170].

TAl LI~UTHAM KHAo

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