Talking With: EDC Biosystems

Drug discovery and development efforts of pharmaceutical companies benefit by decreasing the cost of each assay sample. In addition, it is important to be able to screen and profile candidates in a variety of assays directed toward different targets to understand its specificity. Both desired goals lead to miniaturization of assay samples. At about 100,000 assay samples (i.e., wells), the cost of each assay depends most heavily on the cost of the reagents, including chemical compounds, engineered cells, signal development systems, bioactive materials such as growth factors, and cell media, rather than the cost of the higher-density wellplate and instrumentation. The cost of each sample is directly proportional to its volume. Therefore, the most cost-effective way to improve the number of compounds screened and profiled is to decrease the volume of each assay sample. The consequence of miniaturization is automation of the assay sample construction and signal readout. The advantages are that more assay samples can be run per unit expenditure and the information obtained is both denser and richer. For example, it is possible to screen chemical compounds against a target by running a concentration series of each compound in miniaturized samples for much less cost than at single concentration in larger volumes. This provides secondary screening and enables pharmacological analysis in a single experiment.

2.) How does this technology platform enable laboratory scientists to utilize higher density wellplates?

Acoustic dispensing enables accurate and precise volumetric delivery of subnanoliter volumes of assay reagents to wells with dimensions on the order of a millimeter. The technology eliminates intervening transfer tubes that are a potential source of both sample contamination and dispensing inaccuracy and imprecision. The trademark “True Non-contact Technology” was originally coined in 2000 when EDC Biosystems first built an instrument that would dispense liquid directly out from a wellplate. The potential applications of this platform were great and one of them was to create microarrays. In the year 2000, microarrays were most commonly created using one of two methods. Either capillary tips would aspirate fluid from wellplates to placed droplets onto glass slides or needles with built in channels would wick up the fluid and essentially have brief contact with the coated glass surfaces. However, in either scenario, the printed microarraying solutions would come into “contact” with a foreign object (e.g., a tip of some sort) before reaching its destination. At the time, the term “Non-Contact” was already taken in the microarraying arena that simply described the distinction of spot creation by way of momentarily applying a “piezo squeeze” technique to the end of stainless-steel needles. The resultant drop is ejected from the end of the stainless-steel needle, not requiring contact with the slides.
The spot creation on glass slides by way of “piezo squeezing” a stainless-steel needle does however require the aspiration of liquid before the resultant drop is ejected. In this scenario, the printed microarraying solutions at their source would come into “contact” with a foreign object (e.g., a tip of some sort) during the aspiration step, again, a potential for contamination of the source fluid. Hence, the term “True Non-contact Technology” was coined which best described the complete absence of a foreign object contacting either the source fluid or the target glass slide.

The punch line behind True Non-Contact Technology for pharmaceutical companies in drug discovery, then, is that the dispense volumes for microarrays are typically much smaller than for wellplates and require a far greater degree of drop placement precision. Yields, throughput, and overall cost for that matter, have always been tied with the ability to miniaturize. What True Non-contact Technology enables pharmaceutical companies to do, simply, is to confidently use less compound solution. This ability can either be exploited to achieve greater resolution in experiments, greater mileage from a single compound plate, or enabling the use of higher density plate formats such as the Aurora Biotechnologies 1536 and 3456-well nanoplates, which have been shown to reduce cost throughout the process stream.

3.) How can the “True Non-Contact Technology” platform assist pharmaceutical companies in regards to their liquid compound handling processes?

“True Non-Contact Technology” enables accurate and precise liquid dispensing. This enables construction of microliter-scale volume assays in which the stoichiometric errors of the concentrations of key reagents chemical compounds, or bioactive regulators do not contribute significantly to assay signal variability. Thus, scientists are able to obtain statistical significance rapidly without costly re-testing simply to cover the experimental outcome space. Clearly, “True Non-contact Technology” is more than just a way to dispense liquid. Since the core engine of acoustic technology is a transducer, it also can receive feedback signals as well as transmit the energy used in ejecting a drop of fluid. For every acoustic-wave that is emitted, a portion of it is reflected back after passing through the bulk fluid of interest. A plethora of information can be harvested from that reflected signal such as how far away the liquid surface was from the bottom of the wellplate, the viscosity of the fluid, the density of the fluid, and even the concentration of liquids. The key to all this information is simply in the ability to process the signals received and to correlate the raw data to the information desired.

4.) What is the advantage of reducing the amounts of precious compounds used in biomolecular and assay experiments?

It turns out that reducing amounts of compounds used in biomolecular assay experiments is more than just about saving time, cost, and reagents. Some biomolecular assays are simply not possible unless the reaction surface area and concentration of solution are both optimized. To a certain degree that is why some wellplates have the well geometries that they have.

By reducing the amounts of precious compounds through smaller droplets, you not only reduce overall compound usage, but you can also optimize the reaction area by dispensing several small discreet droplets into the same reaction chamber (i.e., a well in a wellplate). Kinetic studies can then be more precisely timed, cell assays can experience less chemical shock due to over-concentrated boluses, and even spots of microarrays can be optimally charged with the solute over a controlled spot diameter. Too often we observe that it isn’t only about what a biological system sees but how two entities are introduced to each other that either causes or inhibits a particular result. Bottom-line, with the ability to distribute smaller quantities comes another level of control over another important variable in any experimental system.

5.) What benefits does the “True Non-Contact Technology” platform offer pharmaceutical companies in regards to achieving higher yields and increasing overall throughput?

“True Non-Contact Technology” is a fully automated liquid transfer system that is optimized for the small sample volumes necessary to miniaturize assays and automate their performance. This enables the massive parallel replication of assays at the heart of high-throughput experimentation with the attendant benefits of rapidly deriving answers.

6.) How has the technological application of breakthrough discoveries in other fields lent itself to those possibilities in the life sciences arena?

Breakthrough discoveries in other fields have made high-throughput experimentation possible. Liquid dispensing is only one of them. Understanding fluid dynamics at pico to nanoliter scales has enabled the development of dispensing systems that incorporate all the scientific details into the engineering to enable miniaturized assays to perform as well as, if not better than assay samples with traditional volumes.