Copyright © 2010 by ASME
Proceedings of ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology
NEMB2010
February 7-10, 2010 Houston, TX, USA
DEVELOPMENT OF A MICROFLUIDIC INJECTION AND PERFUSION DEVICE FOR SINGLE
CELL STUDY
Hsiu-hung Simon Chen, Zhiquan Shu, Lei Cheng and Dayong Gao
Department of Mechanical Engineering
University of Washington, Seattle WA
USA
Corresponding author: hhchen@u.washington.edu
ABSTRACT
The cell membrane, composed primarily of proteins and lipids, is a selectively permeable lipid bilayer in the scale of 10 nm
or so. Molecules permeating through cell membranes play critical roles in the applications of drug delivery, cell therapy, and
cryopreservation. Cryopreservation and banking of cells, such as umbilical cord bloods, female eggs, etc., are critical to facilitate
practical and effective in vitro fertilization (IVF). The determination of molecule transport properties of cells, such as water and
cryoprotectants (CPAs), is indispensable for developing optimal conditions for cryopreserving them. On the other hand, injection of
material of interests, such as sperms and DNA segments, to female eggs or blastocysts, so-called intracytoplasmic sperm injection
(ICSI) technique, are playing important roles on IVF and advanced gene knock-out. In this study, a novel micro- nano-fluidic system
that allows perfusion and injection in nano-liter scale has been developed and fabricated by soft lithographic methods. A single cell in
the microfluidic system is able to be trapped on site and then either be perfused by various solutions or injected with plain solutions or
solutions with genetic materials. Our ongoing study will demonstrate that the micro- nano-fluidic system allows us to: 1) confine cells
in a channel; 2) deliver drugs by perfusing the cell; 3) monitor osmotic behaviors of the cell by replacing its extracellular environment;
and 4) perform ICSI with sperms or genetic materials.
Keywords: intracytoplasmic sperm injection, cryopreservation, microfluidic, cell therapy.
INTRODUCTION
Osmotic response of cells toward their extracellular
environment plays a critical role in the fundamental study of
cryobiology [1-6]. Molecules permeating through cell
membranes through perfusion allow cell behaviors be
monitored in the applications of drug delivery, cell therapy, and
cryopreservation. On the other hand, direct injection of
materials to cells through tiny needles has also shown its
potentials in transgenic research and genetic engendering [7-9].
Various approaches have been utilized to quantify the
cell membrane transport properties, reviewed by McGrath [10],
and to manipulate single cells [11-14]. On the other hand,
intracytoplasmic sperm injection (ICSI) technique has
performed its successful way in in vitro fertilization (IVF) and
other transgenic experiments. In order to accelerate the
improvement of gene engineering, as well as lower the cost of
performing ICSI related experiment (over USD100,000 for
equipment itself), a cost-effective and easy-to-use system needs
to be developed.
In this study, a micro- nano-fluidic system that allows
perfusion and injection in nano-liter scale has been realized and
fabricated by soft lithographic methods. A single cell in the
microfluidic system will be able to be trapped on site and then
either be perfused by various solutions or injected with plain
solutions or solutions with genetic materials. Before, during
and after the cell is manipulated, cell behavior towards its
extracullular environment will be monitored under the
microscope. Our ongoing study will demonstrate that the
micro- nano-fluidic system should allows us to: 1) confine cells
at a in a channel; 2) deliver drugs by perfusing the cell; 3)
monitor osmotic behaviors of the cell when replacing its
extracellular environment; and 4) perform ICSI with sperms or
genetic materials.
EXPERIMENTAL METHODS
Proceedings of ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology
NEMB2010
February 7-10, 2010 Houston, TX, USA
NEMB2010-13
1 Copyright © 2010 by ASME
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