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Research Papers

Scalable Fabrication of Low Elastic Modulus Polymeric Nanocarriers With Controlled Shapes for Diagnostics and Drug Delivery

[+] Author and Article Information
Vikramjit Singh

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712-1591
e-mail: viks@utexas.edu

Rachit Agarwal

Department of Biomedical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332-0535
e-mail: rachitbly@gmail.com

Patrick Jurney

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712-1591
e-mail: jurney4@gmail.com

Kervin Marshall

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712-1591
e-mail: kervinscott@gmail.com

Krishnendu Roy

Department of Biomedical Engineering,
Georgia Institute of Technology and Emory University,
Atlanta, GA 30332-0535
e-mail: krish.roy@gatech.edu

Li Shi

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712-1591
e-mail: lishi@mail.utexas.edu

S.V. Sreenivasan

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712-1591
e-mail: sv.sreeni@mail.utexas.edu

1Corresponding author.

Contributed by the Manufacturing Engineering Division of ASME for publication in the JOURNAL OF MICRO- AND NANO-MANUFACTURING. Manuscript received April 7, 2014; final manuscript received October 21, 2014; published online November 20, 2014. Assoc. Editor: Nicholas Fang.

J. Micro Nano-Manuf 3(1), 011002 (Mar 01, 2015) (8 pages) Paper No: JMNM-14-1024; doi: 10.1115/1.4028896 History: Received April 07, 2014; Revised October 21, 2014; Online November 20, 2014

A new process, decoupled functional imprint lithography (D-FIL), is presented for fabricating low elastic modulus polymeric nanocarriers possessing Young's modulus of bulk material as low as sub-1 MPa. This method is employed to fabricate sub-50 nm diameter cylinders with >3:1 aspect ratio and other challenging shapes from low elastic modulus polymers such as N-isopropylacrylamide (NIPAM) and poly(ethylene glycol) di-acrylate (PEGDA), possessing Young's modulus of bulk material <10 MPa which is cannot otherwise be imprinted in similar size and pitch using existing imprint techniques. Standard imprint lithography polymers have Young's modulus >1 GPa, and so these polymers used in nanocarrier fabrication in comparison have very low elastic modulus. Monodispersed, shape- and size-specific nanocarriers composed of NIPAM with material elastic modulus of <1 MPa have been fabricated and show thermal responsive behavior at the lower critical solubility temperature (LCST) of ∼32 °C. In addition, re-entrant shaped nanocarriers composed of PEGDA with elastic modulus <10 MPa are also fabricated. Nanocarriers fabricated from PEGDA are shown with model imaging agent and anticancer drug (Doxorubicin) encapsulated in as small as 50 nm cylindrical nanocarriers.

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Figures

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Fig. 1

SEM and AFM images of sub-50 nm diameter NIPAM and PEGDA based nanopillars imprinted using J-FIL: (a) Top-down SEM of nanopillars using standard J-FIL resist with high pattern density template with holes having d = 36 nm, h = 72 nm, and pitch, p = 72 nm; (b) top-down; (c) 15 deg angled cross section SEM of collapsed nanopillars consisting of PEGDA 200 Da in DMSO using the same template as mentioned in (a); (d) AFM of collapsed nanopillars consisting of NIPAM; (e) bad shape retention of PEGDA 700 Da imprints using J-FIL due to elastic relaxation of an imprint using PEGDA 700 Da after imprinting using a template having holes with diameter d = 120 nm, height h = 80 nm, and pitch p = 240 nm; and (f) Nanoimprint of standard J-FIL resist using the same template as (d) showing desired nanopillar geometry.

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Fig. 2

D-FIL process for fabricating nanocarriers in drug delivery applications: (a) illustration and SEM of mechanically stable hole-tone imprint (40 nm diameter holes with 100 nm pitch) over SiOx masked PVA layer on a Si substrate; (b) break-through etch into the SiOx masking layer; (c) transfer of etched pattern with varying depths as shown in SEM images (c1) AR = 1:1, (c2) AR = 2:1, and (c3) AR > 3:1; (d) imprint planarization of patterned PVA layer; (e) removal of top residual layer; and (f) dissolution of PVA layer in DI water to harvest nanocarriers.

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Fig. 3

Illustration depitcting imprinting issues during demolding in conventional imprinting processes (a), compared to the D-FIL process shown in (b)

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Fig. 4

Fabrication of PEGDA nanocarriers using D-FIL: (a) SEM image showing transfer of an imprint pattern (d = 155 nm, h = 160 nm, square array pattern density pitch p = 200 nm) into the PVA layer; (b) SEM image showing imprint planarization of UV cured PEGDA based aqueous resist over the patterned PVA layer; (c) SEM image after RIE etch removal of the top residual interconnecting layer creating isolated PEGDA nanocarriers (d = 155 nm, h = 160 nm) inside the patterned PVA; (d) fluorescence image of released PEGDA nanocarriers; (e) and (f) SEM image of released nanocarriers; and (g) large area (80 mm diameter) imprint planarization of patterned PVA using imprint lithography over a 6 in. Si wafer.

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Fig. 5

SEM and fluorescence images of PEGDA 400 Da nanocarrier: (a) SEM image of imprint planarized isolated sub-50 nm diameter cylindrical nanocarriers with aspect ratio >3:1; (b) SEM image and (c) fluorescence microscopy image of released sub-50 nm diameter cylindrical nanocarriers with aspect ratio >3:1; (d) SEM image of imprint planarized isolated sub-200 nm re-entrant barrel shaped nanocarriers; (e) SEM image and (f) fluorescence microscopy image of sub-200 nm re-entrant barrel shaped nanocarrier; (g) SEM image of imprint planarized 50 nm cylindrical nanocarriers; (h) SEM image; and (i) Fluorescence microscopy image of released 50 nm PEGDA nanocarriers showing encapsulation of Doxorubicin post fabrication and release.

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Fig. 6

NIPAM nanocarriers fabricated using D-FIL: (a) 40 nm diameter cylinders with AR > 3:1 and (b) 100 nm diameter cylinders with AR = 2:1

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