Acoustic droplet ejection (ADE) uses a pulse of ultrasound to move low volumes of fluids (typically nanoliters or picoliters) without any physical contact. This technology focuses acoustic energy into a fluid sample in order to eject droplets as small as a
picoliter. ADE technology is a very gentle process, and it can be used to transfer proteins, high molecular weight DNA and live cells without damage or loss of viability. This feature makes the technology suitable for a wide variety of applications including
proteomics
Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replicatio ...
and cell-based assays.
History
Acoustic droplet ejection was first reported in 1927 by
Robert W. Wood
Robert Williams Wood (May 2, 1868 – August 11, 1955) was an American physicist and inventor who made pivotal contributions to the field of optics. He pioneered infrared and ultraviolet photography. Wood's patents and theoretical work inform m ...
and
Alfred Loomis, who noted that when a high-power acoustic generator was immersed in an oil bath, a mound formed on the surface of the oil and, like a "miniature volcano", ejected a continuous stream of droplets. Ripples that appear in a glass of water placed on a loud speaker show that acoustic energy can be converted to kinetic energy in a fluid. If the sound is turned up enough, droplets will jump from the liquid. This technique was refined in the 1970s and 1980s by
Xerox
Xerox Holdings Corporation (, ) is an American corporation that sells print and electronic document, digital document products and services in more than 160 countries. Xerox was the pioneer of the photocopier market, beginning with the introduc ...
and
IBM
International Business Machines Corporation (using the trademark IBM), nicknamed Big Blue, is an American Multinational corporation, multinational technology company headquartered in Armonk, New York, and present in over 175 countries. It is ...
and other organizations to provide a single droplet on-demand for printing ink onto a page. Two California-based companies, EDC Biosystems Inc. and Labcyte Inc. (both now acquired by
Beckman Coulter
Beckman Coulter, Inc. is a Danaher Corporation company that develops, manufactures, and markets products relevant to biomedical testing. It operates in the industries of diagnostics under the brand name Beckman Coulter and life sciences under the ...
), exploit acoustic energy for two separate functions: 1) as a liquid transfer device and 2) as a device for liquid auditing.
Ejection mechanism
To eject a droplet, a transducer generates and transfers acoustic energy to a source well. When the acoustic energy is focused near the surface of the liquid, a mound of liquid is formed and a droplet is ejected. The diameter of the droplet scales inversely with the frequency of the acoustic energy—higher frequencies produce smaller droplets. Unlike other liquid transfer devices, no
pipette
A pipette (sometimes spelled as pipet) is a type of laboratory tool commonly used in chemistry and biology to transport a measured volume of liquid, often as a media dispenser. Pipettes come in several designs for various purposes with differing ...
tips,
pin tools, or
nozzle
A nozzle is a device designed to control the direction or characteristics of a fluid flow (specially to increase velocity) as it exits (or enters) an enclosed chamber or pipe (material), pipe.
A nozzle is often a pipe or tube of varying cross ...
s touch the source liquid or destination surfaces. Liquid transfer methods that rely on droplet formation through an orifice, e.g., disposable tips or capillary nozzles, invariably lose precision as the transfer volume decreases. Touchless acoustic transfer provides a
coefficient of variation
In probability theory and statistics, the coefficient of variation (CV), also known as normalized root-mean-square deviation (NRMSD), percent RMS, and relative standard deviation (RSD), is a standardized measure of dispersion of a probability ...
(CV) that is significantly lower than other techniques and is independent of volume at the levels tested.
ADE shoots a droplet from a source well upward to an inverted receiving plate positioned above the source plate. Liquids ejected from the source are captured by dry plates due to surface tension. For larger volumes, multiple droplets can be rapidly ejected from the source (typically 100 to 500 droplets/sec) to the destination with the coefficient of variation typically <4% over a volume range of two orders of magnitude.
Applications of acoustic transfer
The following applications are among those that can benefit from the features of acoustic droplet ejection:
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High throughput screening
High-throughput screening (HTS) is a method for scientific discovery especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling device ...
[{{cite journal , first1 = Xingyu , last1 = Yin , first2 = Alexander , last2 = Scalia , first3 = Ludmila , last3 = Leroy , first4 = Christina M. , last4 = Cuttitta , first5 = Gina M. , last5 = Polizzo , first6 = Daniel L. , last6 = Ericson , first7 = Christian G. , last7 = Roessler , first8 = Olven , last8 = Campos , first9 = Millie Y. , last9 = Ma , first10 = Rakhi , last10 = Agarwal , first11 = Rick , last11 = Jackimowicz , first12 = Marc , last12 = Allaire , first13 = Allen M. , last13 = Orville , first14 = Robert M. , last14 = Sweet , first15 = Alexei S. , last15 = Soares , title = Hitting the target: fragment screening with acoustic in situ co-crystallization of proteins plus fragment libraries on pin-mounted data-collection micromeshes , year = 2014 , journal = Acta Crystallographica Section D , volume = 70 , issue = 5 , pages = 1177–1189 , doi = 10.1107/S1399004713034603, pmid = 24816088 , url = http://academicworks.cuny.edu/cgi/viewcontent.cgi?article=1055&context=si_pubs , pmc = 4014116 ]
*
Microelectromechanical systems
MEMS (micro-electromechanical systems) is the technology of microscopic devices incorporating both electronic and moving parts. MEMS are made up of components between 1 and 100 micrometres in size (i.e., 0.001 to 0.1 mm), and MEMS devices ...
*
Assay miniaturization
*
Eliminating cross-contamination
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Reducing plastic waste in biological research
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Direct loading of mass spectrometers
See also
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Acoustic droplet vaporization
Journal of Laboratory Automation Special Issue: Advancing Scientific Innovation with Acoustic Droplet Ejection
References
Acoustics
Ultrasound
Microtechnology
Microfluidics
Nanotechnology