Medical Engineering & Physics 29 (2007) 749–754
Preparation of microbubble suspensions by co-axial
electrohydrodynamic atomization
U. Farook, H.B. Zhang, M.J. Edirisinghe
∗
, E. Stride, N. Saffari
Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
Received 14 June 2006; received in revised form 25 August 2006; accepted 29 August 2006
Abstract
In this paper we report a novel method, based on co-axial electrohydrodynamic jetting, for the preparation of microbubble suspensions
containing bubbles <10 m in size and having a narrow size distribution. No selective filtration is necessary and the suspensions are produced
directly by the process. To demonstrate the method, glycerol was used as the liquid medium, flowing in the outer needle of the co-axial twin
needle arrangement and undergoing electrohydrodynamic atomization in the stable cone-jet mode while air flowed through the inner needle
at the same time. At zero applied voltage a hollow stream of liquid flowed from the outer needle. When the applied voltage was increased,
eventually the hollow stream became a stable cone-jet and emitted a microthread of bubbles, which were collected in a container of glycerol
to obtain microbubble suspensions. The size of the microbubbles was measured via optical microscopy and laser diffractometry. Several
microbubble suspensions were prepared and characterised and the size distribution was found to be critically dependent on the ratio (n) of
flow rates of liquid/air and, in particular the flow rate of the air. At n = 1.5, with the flow rate of air set at ∼1.7 l/s, a microbubble suspension
containing bubbles in the size range 2–8 m was obtained.
© 2006 IPEM. Published by Elsevier Ltd. All rights reserved.
Keywords: Microbubble; Electrohydrodynamic; Co-axial; Atomization
1. Introduction
Suspensions of gas microbubbles play a vital role in a wide
range of sectors including materials and chemical engineer-
ing, environmental engineering and medical engineering. In
the latter case, microbubbles have become well established as
the most effective form of contrast agent for diagnostic ultra-
sound imaging, owing to their high compressibility and their
ability to scatter ultrasound non-linearly. More recently, the
use of coated microbubbles in therapeutic applications such
as targeted drug and gene delivery has also become an active
area of research [1–5]. By incorporating drugs into their coat-
ings, microbubbles may be used as carrier particles that can
be traced through the body using low intensity ultrasound and
then destroyed with a high intensity burst in order to release
the drug in a specific region. By localising the treatment in
this way, the use of microbubbles and ultrasound has become
∗
Corresponding author. Tel.: +44 2076793942.
E-mail address: m.edirisinghe@ucl.ac.uk (M.J. Edirisinghe).
an effective method of tumour therapy [6,7] and the harmful
side-effects from chemotherapy can be reduced. However, for
therapeutic applications, a well-defined microbubble size dis-
tribution, drug content and destruction threshold are critical in
order to ensure correct dosage. The required level of size dis-
tribution control is not easily provided by existing microbub-
ble preparation technologies such as agitation or sonication
[8,9].
Producing microbubble suspensions via agitation or
sonication, results in a broad size distribution and it is
necessary to filter out microbubbles having diameters
>10 m which would pose a risk of causing an embolism
in vivo. Even then, the remaining size distribution is still
relatively broad, resulting in a wide range of microbubble
resonance frequencies. Moreover, there is a wide variation in
the properties of individual microbubble coatings, which has
a significant effect upon their dynamic and acoustic response
[10]. For example, microbubble scattering cross-section
varies with the stiffness of the coating. This makes predict-
ing and controlling the microbubble response, in particular
1350-4533/$ – see front matter © 2006 IPEM. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.medengphy.2006.08.009