Acoustic concentration, transfer and analysis of samples containing particles
Systems and methods described herein employ focused acoustic energy applied to a reservoir containing a fluid to eject a fluid sample from the fluid sample reservoir, e.g. to an inlet of an analytical device. In many embodiments, the ejected fluid sample traverses an air gap separating the inlet of the analytical device from an upper surface of the fluid in the fluid sample reservoir. In many embodiments, the ejected fluid sample comprises one or more droplets ejected from the fluid sample reservoir, which can contain particles suspended in the fluid sample.
1. A method for acoustic transfer of particle-containing fluid droplets, the method comprising:
positioning a fluid sample reservoir containing a fluid sample having suspended cells or particles that is acoustically coupled with an acoustic radiation generator in alignment with an inlet of an analytical device;
applying an ejection tone burst of focused acoustic radiation by the acoustic radiation generator to the fluid sample within the fluid sample reservoir to eject a droplet from the fluid sample reservoir such that the droplet contacts the inlet of the analytical device, the droplet containing at least one cell or particle; and
concentrating the suspended cells or particles at a target location within the fluid sample prior to applying the ejection tone burst by applying a concentrating tone burst of focused acoustic radiation by the acoustic radiation generator to the fluid sample, the concentrating tone burst configured to move the suspended cells or particles toward the target location within the fluid sample without causing droplet ejection.
2. The method of claim 1 , wherein the concentrating tone burst and the ejection tone burst are applied sequentially.
3. The method of claim 1 , further comprising: repeatedly applying the concentrating tone burst to maintain an increased concentration of the cells or particles at the target location within the fluid sample.
4. The method of claim 1 , wherein the concentrating tone burst comprises one of a continuous waveform or a long tone burst configured to produce a standing acoustic wave in the fluid sample to trap the cells or particles in a resonant or anti-resonant node.
5. The method of claim 1 , wherein the concentrating tone burst comprises a swept frequency configured to push the cells or particles toward the target location within the fluid sample.
6. The method of claim 1 , wherein: the acoustic radiation generator comprises an annular first acoustic radiation generator and a disk-shaped second acoustic radiation generator positioned concentric with the first acoustic radiation generator; the concentrating tone burst is generated by the first acoustic radiation generator; and the ejection tone burst is generated by the second acoustic radiation generator.
7. The method of claim 1 , further comprising: subsequent to the ejection of the droplet from the fluid sample reservoir, positioning a second fluid sample reservoir containing a second fluid sample in alignment with the acoustic radiation generator; applying a second concentrating tone burst of focused acoustic radiation by the acoustic radiation generator to the second fluid sample to concentrate cells or particles within the second fluid sample; and applying a second ejection tone burst of focused acoustic radiation by the acoustic radiation generator to the second sample fluid within the second fluid sample reservoir at a second target location corresponding to the concentrated cells or particles, to ejecta second droplet from the second fluid sample reservoir containing at least one cell or particle.
8. The method of claim 1 , further comprising:
adjusting a vertical position of the fluid sample reservoir to align a focal region of the ejection tone burst with an upper surface of the fluid sample.
9. The method of claim 1 , further comprising:
performing a particle count by the analytical device on the droplet contacting the inlet of the analytical device.
10. The method of claim 9 , wherein:
the analytical device comprises an electrolytic particle counter configured to count or measure the suspended cells or particles in the droplet contacting the inlet of the analytical device by measuring electrical impedance of fluid drawn from the droplet across an aperture of the analytical device fluidly coupled with the inlet; and
performing the particle count comprises electrically sensing passage of the suspended cells or particles through the aperture from the droplet contacting the inlet.
11. The method of claim 9 , further comprising:
ejecting additional subsequent droplets from the fluid sample contained in the fluid sample reservoir to supplement the droplet contacting the inlet of the analytical device; and
ceasing ejecting the additional subsequent droplets from the fluid sample based on an attribute of the particle count.
12. The method of claim 11 , wherein the attribute of the particle count is one of a number of cells or particles, a size of cells or particles, a number of cells or particles per unit time, a number of cells or particles within a predetermined range of size, or a total volume passed through the analytical device.
13. The method of claim 11 , wherein the analytical device is configured for counting cells or particle.