Procedia

Chemistry
Procedia Chemistry 1 (2009) 2831
www.elsevier.com/locate/procedia

Proceedings of the Eurosensors XXIII conference

Fabrication and characterization of ultra-thin magnetic films for

biomedical applications
V. Mattolia,b *, V. Pensabenea,b, T. Fujiec, S. Taccolaa, A. Menciassia,b, S. Takeokac,
P. Darioa,b
a
CRIM Lab, Scuola Superiore SantAnna, Pisa, Italy
IIT, Italian Institute of Technology, Morego, Genova, Italy
c
Dept. Life Sci. Med. Biosci., Waseda University (TWIns), Tokyo, Japan
b

Abstract
Polymeric ultra-thin films, so called nanosheets, show peculiar properties making them potentially useful for several applications
in biomedicine. Moreover, the possibility to functionalize these films by using different agents opens new and partially
unexplored scenarios, including micro/nano sensing and actuation. This paper compares two different methods for the
preparation of free-standing nanosheets, loaded with magnetic particles for no-contact manipulation in liquid environment.
Morphology and functionalities of the two types of nanosheets have been characterized and compared. These magnetic
nanosheets could find applications as free-standing carriers to be released and controlled in endoluminal surgery or as plasters
with nanometric thickness to be delivered in situ on surgical incisions.
Keywords: Nanosheets; Free-standing nanosheets; Magnetic particles; Magnetic nanosheets

1. Introduction
Nanosheets are polymer-based films with very large area (up to tens of cm2) and with a thickness in the order of
few tenth hundreds of nanometers1. The peculiar properties this structures make them suitable for different
applications in the biomedical field. Biocompatibility, flexibility and possibility to carry drugs for controlled release
are just some of the most interesting features that nanosheets can exploit2. Anyhow, to be effectively useful in real
applications (e.g. as a plaster for endoluminal surgery, to be delivered in situ on surgical incisions), these structure
should be handled and positioned within the working environment, possibly by using non-invasive external tools. In
this sense, the possibility to include magnetic components, such as magnetic nanoparticles, nanobeads or
microcapsules containing magnetic nanoparticles, will pave the way for the effective use of nanosheets, by allowing
the precise positioning of nanosheets by using an external magnetic field.
This work presents two different types of magnetic controllable free-standing nanosheets based on PLLA (poly(Llactic acid)), loaded with paramagnetic nanoparticles (NPs) and realized by following two different approaches. The
first one, called homogeneous magnetic nanosheet, is fabricated by a single step of spin-coating assisted
deposition (sacrificial layer approach)1 using a PLLA solution containing NPs dispersions. The spin coating process,
already used for embedding gold nanoparticles between two polyelectrolyte layers3, has been here proposed to
implement a completely new, simple and fast nanosheets fabrication process, able to produce a single layer of
1876-6196/09/$ See front matter 2009 Published by Elsevier B.V.
doi:10.1016/j.proche.2009.07.007

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polymer with embedded magnetic nanoparticles. The second type of magnetic nanosheets, called heterogenous
magnetic nanosheet, is a double PLLA nanosheet that includes NPs deposited on the corners, in a multi-step
fabrication process.
2. Materials and methods

2.1. Materials and experimental measurements

Poly(L-lactic acid) (PLLA, Mw: 80-100 kDa) and poly(vinyl alcohol) (PVA, Mw: 22 kDa (99% hydrolyzed))
were purchased from Polysciences Inc. (Warrington, PA) and Sigma-Aldrich Co. (Saint Louis, MO), respectively.
Silicon wafers (200 nm-thick SiO2 substrates, boron doped, crystal face 1 0 0, p-type), purchased from KST World
Co. (Fukui, Japan), were cut into 2x2 cm2 and treated with an acid mixture (SPM: 96% H2SO4: 30% H2O2 = 4:1
(v/v)) at 120C for 10 min washing and then thoroughly rinsed with deionized (D.I.) water (18 Mcm). Iron oxide
Fe2O3 nanoparticles (diameter of 200 nm) were purchased from Toda Kogyo Corp. The thickness of nanosheets was
analyzed by a surface profiler -step (KLA-Tencor Co., San Jose, CA), the macroscopic morphology of the PLLA
nanosheet was photographed by a standard digital camera, while the microscopic morphology of the nanosheets was
observed by using an Hitachi S-4500 field emission Scanning Electron Microscope (SEM), a Keyence Optical
Microscope and a Keyence Atomic Force Microscope (AFM) (used also for thickness measurement). Before the
analysis, the nanosheet samples (both types) were deposited on a clean silicon wafer, thoroughly rinsed with
distilled water and dried for 2 hours.
2.2. Preparation of homogeneous magnetic nanosheets
The homogeneous magnetic nanosheet was fabricated by spin-coating assisted deposition (see Fig 1a). The
preparation steps are reported here in details:
A PVA solution (10 mg/ml in H2O) was spinned at 4000 rpm x 20 s on the silicon square wafer (sacrificial layer);
The sample was dried on a hot plate at 80 C for 1 minute;
A PLLA solution (10 mg/ml in CH2Cl2) containing NPs was spinned at 4000 rpm for 20 s (magnetic nanosheet).
Three different NPs dispersion (10, 1 and 0.1 mg/ml) have been tested for nanosheets procedures.
The sample was dried again on a hot plate at 80 C for 1 minute;
The edges of the deposited film were defined with a cutter and the wafer putted in water: the water dissolved the
sacrificial PVA layer and the magnetic nanosheet started to float (free-standing nanosheets). Addition of PVA
solution in the water acts as a stabilizer making possible nanosheet manipulation.
2.3. Preparation of heterogeneous magnetic nanosheets
The not-homogeneous magnetic nanosheet was prepared by a multi-step fabrication process (see Fig 1a). The
preparation steps are reported here in details:
Two pure PLLA nanosheets (without NPs) were prepared (but not released in water) following the procedure
described in the previous section, with two different wafer sizes (2x2 cm2 and 4x4 cm2);
The larger nanosheet was released in water, caught with a frame, rinsed with water and dried for 2 hours;
4 drops of NPs dispersion (about 80 mg/ml in hexane) were released on the corners of the unreleased smaller
nanosheet, and the complete evaporation of the solvent was allowed;
The dried free-standing nanosheet (kept on the frame) was placed over the unreleased nanosheet and pressed
gently on the surface in order to assure good adhesion between the two films;
The obtained sample was heated in oven at 80C for 30 min to improve the adhesion of the films;
Once defined the edges with a cutter, the sample was put in water in order to dissolve the sacrificial PVA layer.
With this second method, the nanoparticles were entrapped between two PLLA nanosheets, in a sandwich-like
structure named heterogeneous nanosheets.

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30

b)

a)

Fig. 1: (a) Preparation of a homogeneous magnetic nanosheet; (b) preparation of a heterogeneous magnetic nanosheet.

3. Results and discussion

The obtained magnetic nanosheets have an average thickness of in the order of 200 nm and 400 nm respectively
for homogeneous and heterogeneous ones. The microscopic morphology of nanosheets and distribution of the NPs
inside the films have been deeply investigated and some results of measurements are reported in Table 1. While the
heterogeneous nanosheets show large aggregates of NPs, essentially due to the drop deposition (Fig. 2b), (thickness
of aggregates in the order of several microns), the homogeneous method enables to achieve a relatively uniform NPs
dispersion (Fig. 2a, Fig. 3). While the number of aggregates depends on the NPs concentration, the aggregate
dimension seems to be essentially independent (as confirmed also from AFM measurements). In general
nanoparticles aggregates are quite small (tenth of nanoparticles) and show an almost 2-D dimensional organization
(thickness of film over the NPs aggregation measure is about 600-650 nm, independently on the aggregate
extension, indicating a distribution of nanoparticles in a few layers).
b)

a)

1 cm

100 m

1 cm

100 m

Fig. 2: Free-standing homogeneous magnetic nanosheet (NPs 10 mg/ml) (a) and heterogeneous magnetic nanosheet (b), suspended in aqueous
solution. On the right side, optical microscope pictures show the dispersion of magnetic nanoparticles aggregates in each nanosheet type.
Average
Thickness
Area 1: 0 nm
Area 2: 192 nm
Area 3: 583 nm
Area 4: 129 nm
Area 5: 647 nm

Fig. 3: (Left) SEM images of homogeneous PLLA magnetic nanosheets with different NPs concentrations: a) 0.1 mg/ml, a) 1 mg/ml, a)
10 mg/ml. (Right) AFM image (15 m x 22 m) of a homogeneous PLLA magnetic nanosheet (NPs 10 mg/ml).

Magnetic behavior of nanosheets has been verified by evaluating the movement of free-standing nanosheets
suspended in water, using a Neodymium Iron Boron magnet (Br = 350 mT). Both types of nanosheets are easily
controlled (Fig. 4, left) and the movement velocity results directly related to the total amount of paramagnetic NPs

V. Mattoli et al. / Procedia Chemistry 1 (2009) 2831

31

embedded in the films (see Table 1). Nanosheet flexibility has been evaluated by verifying the integrity of the film
after repeated aspirations/injections cycles by using micropipettes with different inlet diameters. From these tests,
the homogeneous nanosheet results much more flexible than the heterogeneous one, being able to be aspired and
injected repeatedly through a 0.75 mm hole fully maintaining its integrity (Fig. 4, right), as well as control
nanosheets without NPs.
Table 1. Measurements results of nanosheet thickness and aggregation (given difference), and calculated total NPs amount per nanosheet.
SAMPLE

Nanosheet
Thickness
(AFM)

Agglomeration
Thickness
(AFM)

Thickness
(Profilometer)

Agglomeration
Thickness
(Profilometer)

Calculated total
amount of NPs
(Stechiometry)

n.a

n.a

215 nm

n.a

0.2 g

Homogeneous nanosheet (NPs 1 mg/ml)

148 nm

< 400 nm

210,4 nm

n.a

2 g

Homogeneous nanosheet (NPs 10 mg/ml)

192 nm

400-450

294,6 nm

~283,4 nm

20 g

n.a

n.a

359,33 nm

~1840,67 nm

160 g

Homogeneous nanosheet (NPs 0.1 mg/ml)

Heterogeneous nanosheet

Fig. 4 (Left): Movement of homogeneous (top) and heterogeneous (bottom) free-standing nanosheets actuated by a permanent magnet. (Right):
Flexibility tests with homogeneous (top) and heterogeneous (bottom) nanosheets: a-b) nanosheet aspiration; c-d) nanosheet injection. While the
homogeneous nanosheet tolerates repeated aspiration/injection cycles, the heterogeneous one is easily broken (arrows indicate the breaking
points).

4. Conclusions
This work presents two spin-coating assisted methods for preparing ultrathin magnetic nanosheets. In the
homogeneous method the basic procedure for single layer polymeric nanosheet fabrication is modified to embed
magnetic nanoparticles inside the nanosheet structure. The heterogeneous method aims to control the position of the
nanoparticles, deposing drops of solution selectively in the corners of the squared nanosheet, to achieve a better
controllability in a precise electromagnetic field. In this case, additional steps are required for optimizing the
process, to evaluate the efficiency of the local dispensing of nanoparticles and to compare these results with the first
method. Due to the fabrication process the homogeneous nanosheets results more flexible than heterogeneous one.
Nevertheless both type of nanosheet are easily controlled by magnetic fields. The possibility to control the
nanosheet position and its movement in liquid environments represents an interesting aspect. These nanostructures
can be modified in terms of biocompatibility, size and flexibility, for moving and positioning them inside the human
body in different fluids and spaces. With defined external magnetic fields, they can be moved during a procedure of
gastroscopy in a stomach full of liquid and thus selectively attached on the mucosal walls, in order to cover, cure or
treat ulcers or injuries. The nanosheets surface can be loaded with drugs to be locally released directly on the target
area, while the nanoparticles can be irradiated and heated for a hyperthermic treatment of the tissue.
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