Nano-Bio Discovery Platforms™

Summary of Breakout Session Discussions

CINT User Workshop

January 20, 2005

Session Leaders: A. Shreve, B. Bunker

Session Speakers: D. Bonnell, P. Grodzinski

The majority of the discussion centered around attempts to identify
types of scientific problems that the biological community believes
could be profitably addressed using a platform approach. This discussion
led to a relatively focused set of scientific issues and technical
capabilities that are of immediate interest, and that CINT could help
address. The challenge that remains is to translate these into the
development of design parameters to be incorporated into the first and
subsequent sets of Nano-Bio Discovery Platforms™.

A few key scientific and technical themes emerged in the discussion. In
general, a need was identified for the manipulation, control and
interrogation of complex biological phenomena within sample regimes
ranging from a few cells to sub-cellular processes. The potential uses
of spatially and temporally resolved probes and manipulation techniques
that could be applied both inside and outside of cells was highlighted.
In terms of interrogation, the ability to study biochemical processes
such as protein phosphorylation or other activation, protein-protein
interactions, enzymatic activity, cytoskeletal restructuring, and
intracellular transport, all in real time (ranging from seconds to
minutes) and with multi-scale spatial resolution, was discussed as a
scientific need. The ability to control interactions of a cell with
membranes and membrane-like assemblies was also presented as a need.
Overall, this discussion of problem areas has helped define the
capabilities that should be targeted for inclusion in a general Nano-Bio
Discovery Platform™, even as the breadth of needed capabilities
highlights the difficulties of providing a single platform that will
achieve all needed functions.

Features that need to be designed into the platforms can be summarized.
First, platforms need to enable the establishment of environmental
conditions in which very small numbers of cells can be maintained. The
platform should provide capabilities for transporting cells and placing
them in specific locations, as well as for exposing them to fluids
containing either required nutrients or chemical/biological stimuli. The
platform needs to contain architectures that can harvest both extra- and
intra-cellular fluids (e.g. MEMs-driven micro-needles or syringes). In
all cases, fluid volumes will be very small (ranging from microliters to
the volume of a single cell). Thus, the fluidics-handling systems must
be adapted for moving small quantities of materials, which likely limits
the use of pressure-driven fluid handling strategies that are used in
most existing microanalytical systems. In addition to handling both
environmental and sampled fluids, the platform needs to be capable of
providing a range of physical inputs (electrical, thermal, optical, or
magnetic) to cells. These can be used either to stimulate desired
behaviors or to manipulate cell components (e.g. use of magnetic
nanoparticles to direct proteins or signaling molecules to specific
locations within cells). It is also important that the platform provide
access to characterization methods that are external to the platform,
with access to sophisticated optical imaging, characterization and
tracking methods being an absolute must. Another desired feature would
be for the platform to enable component analytical separation
capabilities at some level, either for on-chip sensors or for delivery
to external instruments such as mass spectrometers. For detailed
interrogation of molecular interactions, another desired feature is that
the platform provide access to scanning probe capabilities. In all
cases, surface functionalization to control interfacial interactions
will also be critical, if only to inhibit undesired phenomena such as
biofouling and non-specific adsorption of desired components on
microchannel walls. An important point is that, in some cases, it may be
more feasible to provide platform flexibility by developing modular
components with different capabilities that can be readily integrated
with one another to provide the overall set of functions needed for a
particular experiment, rather than trying to build all capabilities into
a single chip. If such an approach is taken, then the grouping of
functions within modular elements and the integration schemes for
putting modules together must be carefully addressed.

Currently, components exist that could provide most of the capabilities
of interest to the workshop participants. However, nothing exists that
resembles an integrated system that could be provided as a \"platform\",
either as a single unit or a set of compatible modular units. There is
also a need to address packaging and configurations that will allow the
platforms to be sufficiently user friendly to be useful in the CINT Core
and Gateway facilities and in the laboratories of users. An initial
effort could involve taking a few simple components, and building a
Phase 1 Discovery Platform™, though this platform might well be more
useful for identifying features that work or don\'t work than for
actually enabling a wide range of user science. However, based on these
results, a Phase II platform can then be designed that could be
anticipated to provide a sufficiently refined and user-friendly
capability that a broad set of users will be attracted to its use.