Labs may eventually be able to count copy numbers of any DNA or RNA sequence from single cells or mixed stains, enabling development of inexpensive genomic alternatives to Fish or CGH oncology testing
Advalytix, a wholly-owned subsidiary of Olympus, has launched a suite of solutions for assay miniaturization in three volume ranges: 1microlitre (ul), 5-50ul, and 50-500ul.
Products introduced to the US market at the Lab Automation meeting in Palm Springs include AmpliGrid, a 1ul assay platform designed for nucleic acid and immuno assays; AdvaLab, a low-cost, integrated immuno assay system powered by surface acoustic waves for volumes of 5-50ul; and PlateBooster, a contact-free MTP mixer without moving parts, for volumes up to 500ul.
"The proven technology upon which these products is based is very exciting, and opens new doors of opportunity for a variety of applications," said Christoph Gauer, CEO of Advalytix.
"For instance, labs may eventually be able to count copy numbers of any DNA or RNA sequence from single cells or mixed stains, potentially enabling the future development of less invasive, inexpensive genomic alternatives to such procedures as Fish and CGH oncology testing, along with screening for common fetal abnormalities and more".
AmpliGrid is a flat glass slide with 48 chemically structured reaction centres that provide unparalleled sensitivity and robustness for robot-compatible microlitre reactions.
In comparison to conventional reaction containers such as micro titer plates (MTP), cuvettes and tubes, it provides significant reagent savings by safely holding 1ul reaction volumes in place.
In applications such as common polymerase chain reaction (PCR) or cycle sequencing, it can enable substantial savings with minimal modification to the user's high-throughput facility.
The flat geometry of the slide makes it easy to pre-spot reaction mix directly into the reaction centers, eliminating the need to apply reagents during sample processing.
An activated version of AmpliGrid allows for immobilisation of capture probes directly within the reaction centres, enabling integrated detection without transferring and reformatting amplicons.
The flat geometry also eases monitoring of single cells and placing them into the reaction centres, making it useful for performing diagnostics on single cells or small cell clusters.
The high sensitivity of the AmpliGrid technology allows genomic diagnostic tests on single cells (which is the reason AmpliGrid was chosen as the physical platform for a kit to detect all chromosomes on human polar bodies; the kit is commercially available in Germany).
Further molecular diagnostic assays based on the AmpliGrid platform are currently under development.
For assays in the 5-50ul range, and potentially below, Advalytix offers AdvaLab, a custom system based on a low-cost plastic cartridge that slides into a simple analyser.
A transducer chip inside the analyser generates surface acoustic waves that penetrate the cartridge where they perform dosing, mixing and washing for the assay.
Advalytix says it has proven Saw's reliability and effectiveness through its SlideBooster microarray hybridisation stations.
The cartridge approach allows for low cost, maintenance-free analysers, which make low-throughput analysers economically viable.
For traditional, high-throughput analysers used by reference labs, there is a significant reduction in cost of goods derived from reduced assay volumes.
PlateBooster is a general-purpose laboratory mixer or add-on for liquid handling systems, replacing high-speed orbital shakers and aspiration with pipettes.
Unlike aspiration-based mixing, it mixes contact-free.
The system has no moving parts and operates silently and vibration-free, eliminating interference with sensitive robotic arms, and differentiating it from mechanical mixers.
Thus, PlateBooster is optimised for automated liquid handling platforms.
Applications include re-suspending lyophilised or crystallised reagents for high throughput screening (HTS) and preventing settling of cells or magnetic particles in assays.
In these applications, PlateBooster's advantage over orbital shakers is that its surface acoustic waves penetrate the bottom of MTP wells and mix liquid from the bottom up.
Also, surface acoustic waves operate at much higher frequencies but lower power than conventional ultrasonic waves and therefore do not suffer from the damaging effects associated with ultrasound.
About miniaturized assays In medical diagnostics, current assay volumes for immuno and chemistry assays are in the 200-400ul range with manufacturers now working on assays in the 10-100ul range.
Smaller assays significantly reduce cost of goods and enable smaller, less complex instruments.
Similarly, oligonucleotide amplification and sequencing, currently performed with 5-25ul assays, are being miniaturised to improve cost/ reaction economics.
Volume reductions pose unique challenges.
A 10x reduction of assay volumes for medical diagnostics requires a new approach to mixing: conventional, mechanical mixing is less effective at reduced volumes and more costly to implement.
Other requirements include higher precision for dosing and more sensitive detection technologies.
A 10x volume reduction in oligonucleotide and sequencing assays changes the fundamental physical properties of the assay such as surface tension.
Conventional reaction containers such as MTPs or cuvettes are no longer adequate to ensure efficient reactions and quality control.
Surface tension can cause 1ul drops to 'stick' to an MTP wall rather than react with each other and reactions are difficult to monitor on the bottom of a well.
Advalytix, a wholly owned subsidiary of Olympus Life and Material Science Europa, is said to be at the cutting edge of developing low-cost and simple miniaturised assays based on proprietary intellectual property in surface acoustic wave (Saw) and surface chemistry, as well as providing deep application know-how in microarrays, molecular diagnostics and immuno assays.
Advalytix works with collaborative partners to further advance medical diagnostics based on next generation immuno and chemistry assays and genetic analysis.
