Listening to the Micro-World

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Technologies associated with looking at the microworld are extremely mature, and include a wide variety of microscopies. By contrast little work has been done to extend our sense of hearing into the micro-world. The purpose of this grant is to develop a basic technology for listening to the micro world, in as sense a micro ear.Just like our own ears, most sound detectors respond to changes in pressure, creating small acoustic forces and corresponding displacement of a sensor. One extremely sensitive way of measuring force is to compare it against the momentum of a light beam. Tightly focused laser beams are now routinely used to form optical tweezers, which can trap micron-sized beads, overcoming both the thermal and gravitation forces. These tweezers systems are typically built around a microscope and manipulate samples suspended in a fluid medium / such that the technology is highly compatible with biological systems. Using a microscope to observe the bead position allows the measurement of piconewton forces and the corresponding displacement of a few nanometres. The subtle movements of these optically trapped beads will form the basis of our micro-ear. We plan to develop, demonstrate and test a number of different micro-ear approaches. All imaging systems based upon focusing are restricted to scales of a wavelength or so. Even in water, acoustic wavelengths are 100s mm, making the concept of focussing irrelevant to microscopic systems. However, as evident by most wind instruments or antique hearing aids, sub wavelength horns still work. In this proposal we plan to use microfabrication techniques to produce structures that channel the fluid flow from the emitting object to the sensor bead, providing a method of guiding the pressure wave, and if necessary amplifying it (e.g. in a flared channel). We will use the optically trapped beads as sensors to measure these forces (as described above). However, it is important to consider that, at the microscale, the movements of the beads due to an acoustic response may be masked by Brownian motion / and hence distinguishing the real signal from this thermal background will be a major challenge challenge.The key to overcoming the Brownian background will be the use of high-speed cameras to measure the position of many beads simultaneously. Rather than the signal being derived from one bead, it is the correlated motion of the beads that distinguishes the sensor response from the uncorrelated background. We envisage two basic configurations. In the first, simplest case, the beads will be positioned at the ends of defined flared microfluidic structures to measure molecular interactions resulting from mechanical biological systems (molecular motors). Alternatively, we will create a circular array around the test object and measure the radial breathing of the ring. In this latter configuration there is the possibility of being able to make new and exciting biological measurements in a non-contact mode, where we will determine both short and long range interactions between cells and surfaces.

Publications

10 25 50
 
Description Theme 1:
When two microscopic objects approach each other within a fluid the dominant forces are those associated with
hydrodynamics. Unlike the macroscopic world around us, it is now the velocity of only a one of the particles that leads to a
force acting on the other. Newton's laws of motion are now, in effect, replaced by those of hydrodynamics - leading to
strange behaviours.
Using high speed cameras to monitor the acoustic motion of the particles we were able to observe a new phenomenon
where the random motions of neighbouring systems were synchronised to each other without losing their own randomness.
This hither to unrecognised synchronisation may be key to understanding the collective motion of micro biological systems
The technology we used to make these measurements was transferred to a British SME under the Easy Access IP policy
pioneered by Glasgow University.
Theme 2:
We also developed a substantial body of work, exploiting the knowledge that acoustic waves contain a mechanical energy
that can be used to manipulate fluids. This allowed us to develop a novel and significantly improved method for performing
more complex fluid manipulations. Our new platform involves the principle of using surface acoustic waves (SAW), but,
unlike all previous work in the field, the acoustic energy in the ultrasonic waves is either reflected, refracted or scattered to
create complex waves patterns by using a phononic lattice.
A phononic lattice or crystal is a miniaturised array of mechanical elements that modulates the sound in a manner that can
be understood by considering the optical analogy "shaping" or "patterning" light using a hologram. However, whilst an
optical pattern is created by exploiting the differences in refractive indices within the elements of the hologram, the
ultrasonic field is modulated by the elastic contrast between the elements in the array and the matrix surrounding them.
When the phononic crystal is placed in the path of the SAW, the acoustic energy undergoes a series of reflections and
refractions, to create a new acoustic field. It does this by exploiting the elastic contrast of the materials making up the
structure of the array, together with the size and pitch of the pattern. This leads to a complex but highly controllable,
frequency dependent patterns of acoustic field intensities, which propagate into fluid. As these complex acoustic fields
reach the fluid they create pressure differences in the fluid, resulting in unique flow patterns.
Excitingly, we have gone on to show that instead of fabricating the phononic lattice directly into the piezoelectric chip
(which would involve using the expensive piezoelectric substrate as a diagnostic substrate), we can create the phononic
pattern in a low cost disposable chip (glass, ceramic composite or laminated card) that we can interface with the
piezoelectric substrate.
The different frequencies of ultrasound interact with different phononic structures to give different functions, providing a
"tool-box" of different functions (sample processing, cell separation, detection). Just as in electronics, where discrete
components are combined to create circuits, so we propose to combine different phononic lattices into a single pattern, to
create fluidic microcircuits. In such an architecture, many phononic structures will be overlaid or embeded into each other,
so that each structure will deliver a unique sample processing step to the stationary drop, at a different frequency. Using
these methods we have shown acoustic focussing, heating and cell lysis, integrating the techniques for e.g. on-chip
detection of malaria in blood.
To continue this work, we have received further funding from Bill & Melinda Gates Foundation and it has been the subject
of two patent applications. A company is to be formed shortly with venture money raised from IPGroup.
Exploitation Route See above
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The formation of company SAWDx and consequent exploitation and technology transfer
First Year Of Impact 2012
Sector Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Bill and Melinda Gates Foundation
Amount £61,728 (GBP)
Funding ID OPP1032927 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 06/2011 
End 06/2012
 
Description Bill and Melinda Gates Foundation
Amount £61,728 (GBP)
Funding ID OPP1032927 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 05/2011 
End 10/2012
 
Description EPSRC
Amount £371,492 (GBP)
Funding ID EP/I007822/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 06/2011 
End 01/2014
 
Description EPSRC
Amount £80,248 (GBP)
Funding ID EP/I034726/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2011 
End 07/2012
 
Title FLUIDICS APPARATUS AND FLUIDICS SUBSTRATE FOR SURFACE ACOUSTIC WAVE MANIPULATION OF FLUID SAMPLES 
Description Use of SAW to manipulate fluid samples 
IP Reference WO2011023949 
Protection Patent granted
Year Protection Granted 2011
Licensed Commercial In Confidence
Impact Underpins formation of SAWDx company
 
Title FLUIDICS APPARATUS FOR SURFACE ACOUSTIC WAVE MANIPULATION OF FLUID SAMPLES, USE OF FLUIDICS APPARATUS AND PROCESS FOR THE MANUFACTURE OF FLUIDICS APPARATUS 
Description Devices to manipulate fluids using SAW 
IP Reference WO2012114076 
Protection Patent granted
Year Protection Granted 2012
Licensed Commercial In Confidence
Impact Underpins formation of company SAWDx
 
Title SAMPLE NEBULIZATION 
Description SAW and phononic methods to nebulize samples 
IP Reference PCT/GB2012/0 
Protection Patent granted
Year Protection Granted 2012
Licensed Commercial In Confidence
Impact Underpins formation of company SAWDx
 
Company Name SAWDx 
Description Exploitation of phononic and SAW based technologies in the field of diagnostics 
Year Established 2012 
Impact Currently commercially confidential