The Applied Miniaturisation Lab's Gallery

Some phenomena lend themselves to a good image or movie... but this is not always the case. The next section is a collection of several interesting images collected from our LOC application development. This only gives a narrow slice of what we are doing, please see our recent publications for more complete details (here).

Table 1. Demonstrations

Image	Abstract	Image	Abstract
.	This work explored on-chip self-assembly of fluorescent label and DNA for high resolution, high sensitivity analysis - see Sieben/2005. To try the movie, click on the image. (depending on browser, you may have to save and play the movie)		Fluorescence in-situ hybridization (FISH) is an important cytogenetic technique. We demonstrated significant improvements in the performance of chip-based FISH - see Sieben/2007.
.	This 'dancing cell' demonstrates the degree of control that LOC allows at the level of single copies of cells or DNA. To try the movie, click on the image. (depending on browser, you may have to save and play the movie)		We have developed new methods of wide-angle cytometry that allow for full scatter images to be obtained from single cells. We have also developed new ways of simulating these images. The pattern shown here is a simulation of the scatter from a single cancer cell. See Su/2007 or Pilarski/2008.
	Coming soon...		Much of our data is in the form of an electropherogram (shown here) - a graph of fluorescence vs time that allows us to monitor the passage and presence of DNA. The velocity of the DNA can be related to size, genetic sequence and mutational status. This analysis is very versatile - allowing the detection of disease predisposition (e.g. Footz/2004) or pathogens (e.g. Kaigala/2006).

We have been pleased to have been invited to provide cover pages for some of the journal issues we have published in. These figures have ranged from self-assembled DNA to waveguides and microvalves. Please click on the image to see the related cover image, or see the publication list for more complete details (here).

Table 2. Journal Cover Pages

Image	Abstract	Image	Abstract
.	In this early work we demonstrated the integration of several mutation-detection methods onto a single chip and applied this to the detection of haemochromatosis. (Footz/2004)	.	A key challenge to building cost-effective systems is to produce inexpensive integrated optical components. Here we demonstrate such systems in application to DNA analysis. (Bliss/2007)
.	We recently demonstrated the cost effective integration of a complete diagnostic system - amplification and analysis for less than $1000. (Please see Kaigala's 2008 Analyst paper)	.	We recently demonstrated a readily scaled, easily integrated, electrically actuated microvalve. We believe that this could greatly aid in reaching higher levels of lab on chip integration. (Please see Kaigala's 2008 Lab Chip microvalve paper)

Much of our development is of the systems to operate the "lab on chip" (LOC) devices. We have established a skill set in building extremely inexpensive systems (less than a thousand dollars). These systems are made in-house from electronics, optics and machined components and are several orders of magnitude less expensive than conventional systems. We hope that these may one day serve as prototypes of new medical diagnostics. (Where marked, please click to go to relevant publications)

Table 3. Systems and Instruments

Image	Abstract	Image	Abstract
	For many years our workhorse was Micralyne's Microfluidic Toolkit (or uTK) - a sophisticated LOC electrophoretic system based on confocal laser-induced fluorescence detection. (Caliper and others have similar systems).	.	As of late we developed the "Tricorder Toolkit", or TTK. This gives pump, valve and temperature as well as electrophoretic control, allowing complete LOC diagnostics. This system is comprised of less than $1000 in components! (Please click to see Kaigala's 2008 Analyst paper).
	The latest version of the TTK is one that has been modularised, calibrated, standardised and 'connectorised'. We refer to these systems as the "Next Generation TTKs".	.	At the same time that we develop our TTKs, in a collaboration with VLSI experts (Elliott et al.), we are miniaturising our system electronics and detection systems onto a single microelectronic chip! One of our resulting systems (hand sized) is shown here (USB2).

Of course, a LOC instrument is of little use without the microchips themselves. Here we present a brief overview of some of the chips we have developed, largely based on integrations of genetic amplification (PCR) and analysis (electrophoresis). Together with the above systems, these chips enable the implementation of a wide range of nanobiotechnologies - in particular, medical diagnostic applications.

Table 4. Microchips

Image	Abstract	Image	Abstract
.	The long-standing standard chip for use with the uTKs was the simple cross chip and its variants sold by Micralyne for LOC electrophoresis. Despite its simplicity it was effective - see Footz/2004 for example.		Later generations of the uTK were able to control electrophoresis from as many as 8 reservoirs. The chip used for this (Micralyne) is shown here.
	CMC Microsystems set up rapid prototyping manufacture through Micralyne's Protolyne foundry service. One of these chips is shown here.		Much of our electrophoretic developments were based on these postage-stamp sized "4 Port Minis".
.	Much of our present development is done on microscope-slide sized chips such as that shown here (PCR/CE4). This chip combines microvalves, pumps, electrophoretic and temperature control to enable genetic amplification and analysis directly from a raw sample.	.	Although much of our work uses the microvalve technology developed by Mathies, we are constantly seeking more compact designs and new technologies. The chip shown here combines an electrically-actuated phase-change valves to control genetic amplification.
	Although the microscope-slide sized chips are convenient to prototype with, LOC technologies must ultimately be very small. To explore higher densities we are developing progressively smaller PCR/CE chips such as that shown here (PCR/CE5) - combining all functionalities needed on a postage stamp-sized chip.		In systems such as the uTK much of the overall system cost (tens of thousands of dollars) is due to the high voltage power supply, distribution, switching and interface. The chip shown here uses DALSA's HV CMOS technology to put the entire HV subsystem on a single chip costing on the order of dollars. This could greatly aid in making LOC technologies more available.

The research activities of the AML are directed towards the use and development of microsystems and the nanotechnologies implemented upon them. This field (LOC) is a highly dynamic one with exciting work being performed around the world, much of it with the goal of revolutionizing healthcare. These images may have helped describe what we do... but please read our publications and research sections to get the full flavour. This approach takes teamwork with the development of common infrastructure used by all. Although we have a very interdisciplinary environment, most of the people in the AML develop an area of particular emphasis and interest - e.g. electronics & optics, molecular biology, microfabrication, simulation or fundamental theory. We have a full set of facilities from design and manufacture in our own labs, to joint development of applications with healthcare partners. There is much to do, and a great need for it to be done.