# US 8,770,691 B2 · Acoustically ejecting a droplet of fluid from a reservoir by an acoustic fluid ejection apparatus

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- Number: US 8,770,691 B2
- Document ID: US8770691B2
- Status: Granted
- Kind: B2
- Application number: 12/721,389
- Filed: 2010-03-10
- Published: 2010-07-08
- Granted: 2014-07-08
- Earliest claimed: 2004-10-01
- Assignees: Labcyte Inc.
- Applicants: Richard Stearns; Shehrzad Ahmed Qureshi
- Inventors: Richard Stearns; Shehrzad Ahmed Qureshi
- Web page: https://patentgrep.com/patent/US8770691B2

## CPC

- B05B 12/004: {comprising sensors for monitoring the delivery, e.g. by displaying the sensed value or generating an alarm (B05B12/08 takes precedence; registering or indicating the condition or the working of machines or other apparatus in general G07C3/00)}
- B01L 3/0268: {using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries}
- B41J 2/04541: {Specific driving circuit}
- B41J 2/04575: {controlling heads of acoustic type}
- B41J 2/14008: {Structure of acoustic ink jet print heads}
- B01J 2219/00362: Acoustic nozzles
- B01J 2219/00378: Piezoelectric or ink jet dispensers
- B01J 2219/00527: Sheets
- B01J 2219/00677: Ex-situ synthesis followed by deposition on the substrate
- B01L 2200/143: Quality control, feedback systems
- B01L 2200/148: Specific details about calibrations
- B01L 2300/0819: Microarrays; Biochips
- B01L 2400/0436: acoustic forces, e.g. surface acoustic waves [SAW]
- B01L 2400/0439: ultrasonic vibrations, vibrating piezo elements
- B41J 2/04563: {detecting head temperature; Ink temperature}
- B41J 2/0458: {controlling heads based on heating elements forming bubbles}
- B05B: SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES (spray-mixers with nozzles B01F25/72; processes for applying liquids or other fluent materials to surfaces by spraying B05D)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B41J: TYPEWRITERS; SELECTIVE PRINTING MECHANISMS, i.e. MECHANISMS PRINTING OTHERWISE THAN FROM A FORME; CORRECTION OF TYPOGRAPHICAL ERRORS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

The invention provides apparatuses and methods for acoustically ejecting the fluid from a reservoir contained in or disposed on a substrate. The reservoir has a portion adapted to contain a fluid, and an acoustic radiation generator is positioned in acoustic coupling relationship to the reservoir. Acoustic radiation generated by the acoustic radiation generator is transmitted through at least the portion of the reservoir to an analyzer. The analyzer is capable of determining the energy level of the transmitted acoustic radiation and raising the energy level of subsequent pulses to a level sufficient to eject fluid droplets from the reservoir. The invention is particularly suited for delivering fluid from a plurality of reservoirs in an accurate and efficient manner.

## Claims

### Claim 1

An apparatus for acoustically ejecting a droplet of fluid from each of a plurality of reservoirs comprising:
a plurality of fluid reservoirs contained in or located on a substrate;
a quantity of fluid disposed in each reservoir of the plurality of fluid reservoirs;
an acoustic radiation generator for generating at least one pulse of acoustic radiation;
a means for successively acoustically coupling the acoustic radiation generator with each reservoir such that at least one pulse of acoustic radiation generated by the acoustic radiation generator is transmitted through the substrate and into the fluid to a site at or near the surface of the fluid in each reservoir in a manner effective to eject a droplet from each reservoir acoustically coupled to the acoustic radiation generator; and
an analyzer for determining, prior to acoustically ejecting a droplet of fluid from a reservoir, the wave form of a droplet-forming pulse of acoustic radiation to be generated, wherein the analyzer is further configured to determine an amplitude for the droplet-forming pulse which is sufficient to eject a fluid droplet;
wherein the analyzer is further configured to, for determining the amplitude for the droplet-forming pulse for a reservoir:
(i) acoustically couple an acoustic ejector with the reservoir;
(ii) activate the acoustic ejector to generate and direct a perturbation pulse into the reservoir such that the surface of the fluid is disturbed but no fluid droplet is ejected;
(iii) generate a perturbation interrogation pulse directed at the surface of the fluid;
(iv) detect a reflection of the perturbation interrogation pulse from the surface of the fluid; and
(v) process the reflection detected in step (iv);
wherein the processing of step (v) includes analyzing the frequency spectrum of a portion of the reflection detected in step (iv);
wherein the processing of step (v) includes using a frequency domain-based algorithm to identify the difference in frequency between two minima of the frequency spectrum of the reflection detected in step (iv).

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein an echo portion of the reflection detected in step (iv) is identified.

### Claim 3 (depends on 2)

The apparatus of claim 2, wherein the echo portion is less than 1% of the reflection detected in step (iv).

### Claim 4 (depends on 1)

The apparatus of claim 1, wherein the frequency domain-based algorithm is a Fast Fourier Transform-based algorithm.

### Claim 5 (depends on 1)

The apparatus of claim 1, wherein the perturbation pulse and the droplet-forming pulse have a similar frequency spectrum.

### Claim 6 (depends on 1)

The apparatus of claim 1, wherein the perturbation pulse and the droplet-forming pulse are centered at frequencies within 100 MHz of each other.

### Claim 7 (depends on 3)

The apparatus of claim 3, wherein frequencies at which the perturbation pulse and the droplet-forming pulse are centered lie between 1 MHz and 200 MHz.

### Claim 8 (depends on 1)

The apparatus of claim 1, wherein the time elapsed between the perturbation interrogation pulse and the droplet-forming pulse is no more than 1 millisecond.

### Claim 9 (depends on 1)

The apparatus of claim 1, wherein the time elapsed between the perturbation interrogation pulse and the droplet-forming pulse is no more than one second.

### Claim 10 (depends on 1)

The apparatus of claim 1, wherein the time elapsed between the perturbation interrogation pulse and the droplet-forming pulse is no more than 1 hour.

### Claim 11 (depends on 1)

The apparatus of claim 1, wherein the time elapsed between the perturbation pulse and the perturbation interrogation pulse is no more than 10 milliseconds.

### Claim 12 (depends on 1)

The apparatus of claim 1, wherein the duration of the perturbation pulse is between 0.5 μseconds and 1000 μseconds.

### Claim 13 (depends on 6)

The apparatus of claim 6, wherein the acoustic energy of the perturbation interrogation pulse is between 80% and 120% of the acoustic energy of the droplet-forming pulse.

### Claim 14 (depends on 6)

The apparatus of claim 6, wherein the duration of the droplet-forming pulse is between 0.5 μseconds and 1000 μseconds.

### Claim 15 (depends on 1)

The apparatus of claim 1, wherein the perturbation pulse is at least 0.5 dB lower in power that the droplet-forming pulse.

### Claim 16 (depends on 1)

The apparatus of claim 1, wherein the acoustic radiation generator is a single acoustic radiation generator.

### Claim 17 (depends on 1)

The apparatus of claim 1, wherein the fluid reservoirs and the quantities of fluid within the fluid reservoirs are removable from the remainder of the apparatus.

### Claim 18 (depends on 1)

The apparatus of claim 1, wherein the fluid reservoirs are individual wells in one or more well plates.

### Claim 19 (depends on 1)

The apparatus of claim 1, wherein the fluid reservoirs are substantially acoustically indistinguishable.

### Claim 20 (depends on 1)

The apparatus of claim 1, wherein the fluid reservoirs are optically opaque.

### Claim 21 (depends on 1)

The apparatus of claim 1, wherein the fluid reservoirs are sealed.

### Claim 22 (depends on 1)

The apparatus of claim 1, wherein the apparatus comprises 96 reservoirs.

### Claim 23 (depends on 22)

The apparatus of claim 22, wherein the apparatus comprises 384 reservoirs.

### Claim 24 (depends on 23)

The apparatus of claim 23, wherein the apparatus comprises 1536 reservoirs.

### Claim 25 (depends on 24)

The apparatus of claim 24, wherein the apparatus comprises 3456 reservoirs.

### Claim 26 (depends on 25)

The apparatus of claim 25, wherein the apparatus comprises 10,000 reservoirs.

### Claim 27 (depends on 26)

The apparatus of claim 26, wherein the apparatus comprises 100,000 reservoirs.

### Claim 28 (depends on 27)

The apparatus of claim 27, wherein the apparatus comprises more than 500,000 reservoirs.

### Claim 29 (depends on 1)

The apparatus of claim 1, wherein at least one reservoir is constructed to contain no more than about 1 mL of fluid.

### Claim 30 (depends on 1)

The apparatus of claim 1, wherein at least one reservoir is constructed to contain no more than about 1 ÅL of fluid.

### Claim 31 (depends on 30)

The apparatus of claim 30, wherein at least one reservoir is constructed to contain no more than about 1 nL of fluid.

### Claim 32 (depends on 1)

The apparatus of claim 1, wherein the fluid in the fluid reservoirs is an aqueous fluid.

### Claim 33 (depends on 1)

The apparatus of claim 1, wherein the fluid in the fluid reservoirs is a non-aqueous fluid.

### Claim 34 (depends on 33)

The apparatus of claim 33, wherein the nonaqueous fluid comprises an organic solvent.

### Claim 35 (depends on 1)

The apparatus of claim 1, wherein the fluid contains a biomolecule.

### Claim 36 (depends on 1)

The apparatus of claim 1, wherein the fluid is at least partially frozen.

### Claim 37 (depends on 1)

The apparatus of claim 1, wherein at least one reservoir contains a substance capable of existing as a fluid at a temperature of about 0° C. to about 100° C.

### Claim 38 (depends on 1)

The apparatus of claim 1, further comprising a means for altering the relative position of the analyzer with respect to the fluid reservoirs.

### Claim 39 (depends on 1)

The apparatus of claim 1, wherein the analyzer is positioned in fixed alignment with respect to the acoustic radiation generator.

### Claim 40 (depends on 1)

The apparatus of claim 1, wherein the acoustic radiation generator comprises a component common to the analyzer.

### Claim 41 (depends on 40)

The apparatus of claim 40, wherein the component common to the acoustic radiation generator and the analyzer is a piezoelectric element.

### Claim 42 (depends on 1)

The apparatus of claim 1, wherein the analyzer is adapted to analyze a characteristic of acoustic radiation to determine a property of the fluid in each reservoir.

### Claim 43 (depends on 42)

The apparatus of claim 42, wherein the property is acoustic impedance.

### Claim 44 (depends on 42)

The apparatus of claim 42, wherein the property is acoustic attenuation.

### Claim 45 (depends on 42)

The apparatus of claim 42, wherein the characteristic is the intensity of the acoustic radiation.

### Claim 46 (depends on 42)

The apparatus of claim 42, wherein the characteristic is the wavelength of the acoustic radiation.

### Claim 47 (depends on 40)

The apparatus of claim 40, further comprising a focusing means for focusing acoustic radiation generated by the acoustic radiation generator.

### Claim 48 (depends on 47)

The apparatus of claim 47, wherein the focusing means is adapted to focus the acoustic radiation according to results of an analysis performed by the analyzer.

### Claim 49 (depends on 1)

The apparatus of claim 1, further comprising a temperature control means for controlling the temperature of the fluid reservoirs.