research activities in 2007 - CSEM

Parallel Nanoscale Dispensing of Liquids for Biological Analysis
A. Meister, J. Przybylska, P. Niedermann, C. Santschi, M. Liley, H. Heinzelmann
Nanoscale dispensing (NADIS) is a technique developed at CSEM to dispense ultrasmall volumes of liquid using specifically fabricated scanning
force microscopy probes. The NADIS probes consist of hollow cantilevers connected to a reservoir located in the chip body. Arrays of NADIS
probes have been developed and produced by micromachining in order to dispense biological liquids in parallel.
The precise handling of liquids with volumes in the femto- and
attoliter range is a challenging task, and one that is becoming
increasingly important for specific applications. For example,
local surface functionalization with biomolecules is used to
create high-density microarrays for diagnostics and biology. In
the future, local application of candidate drugs or
nanoparticles on biological cells may be used to study their
influence on the cell in pharmacology or cytotoxicology.
In CSEM’s nanoscale dispensing, or “NADIS”, the ability to
dispense ultrasmall volumes of liquid at precise positions on a
sample is made possible by combining scanning force
microscopy (SFM) with a custom designed microtool. The
NADIS microtool is similar to a standard SPM probe, except
that the cantilever and the tip are hollow. The microfabrication
process for the NADIS cantilevers is shown in Figure 1.
Figure 1: Fabrication process of the NADIS cantilever probes. a) A
wafer is structured with reservoirs and V-grooves for chip release.
b) A second wafer is processed for microfluidic channels and
pyramidal tips with a silicon nitride layer. c) The pre-structured wafers
are brought together and aligned. d) The wafers are fusion bonded
and a silicon oxide layer is grown by thermal oxidation. e) The hollow
cantilever is released by wet etching. f) The chip is released.
Figure 2: Example of glycerol droplets (left, optical micrograph)
deposited with a tipless NADIS probe (right, SEM micrograph)
The hollow core of the cantilever is instrumental for the
dispensing process as it connects an aperture in the cantilever
tip to a liquid reservoir in the body of the chip. Once the
reservoir is filled with liquid, the hollow cantilever and tip will
be filled by capillarity. Transfer of liquid from the tip aperture to
the surface occurs when the tip is brought into contact with the
sample. First proof of principle experiments demonstrating
NADIS dispensing with glycerol are shown in Figure 2.
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In order to increase NADIS throughput, systems with multiple
cantilevers were developed. Various designs were defined,
with different cantilever geometries and dimensions. Some of
them are shown in Figure 3 and 4. Different microfluidic
connections between the cantilevers and the reservoirs were
also designed. All cantilevers in an array can be connected to
one reservoir, so that all dispense the same liquid. Or, if
different liquids are to be dispensed, each cantilever can be
connected to its own reservoir. Cantilevers with a double
beam structure are connected to an inlet and an outlet
reservoir, allowing rinsing of the cantilever by flushing a liquid
through it. Tests of these new systems are now underway.
Figure 3: Optical micrograph of two chips with NADIS probe arrays of
different designs (scale bar: 500 µm). The chips are still attached to
the wafer.
Figure 4: Scanning electron microscope (SEM) micrographs of
NADIS probes. a) Array of NADIS probes. b) Detail of an array.
c) Close-up head-on view of a pyramidal shaped tip. d) Detail of a tip
with the aperture at its apex.
The partial support of the Swiss Federal Office for Education
and Science (OFES) in the framework of the EC-funded
Project NaPa (Contract no. NMP4-CT-2003-500120) is
gratefully acknowledged.