Ultrafast microliter centrifuge platform for size‐based separation using novel omnidirectional spiral surface acoustic wave for point‐of‐care diagnostics

Abstract

Lab‐on‐a‐chip diagnostic devices have long promised the future ability to provide point‐of‐care information on a patient’s medical conditions from a small blood sample. Within the blood, there are numerous functional entities, including exosomes, microRNA, large functional proteins within the plasma and indeed platelets and white blood cells that altogether can provide a great deal of details regarding a patient’s burden of disease and disorders.Despite years of investment and research, none have found a method to perform rapid and effective centrifugation and separation of cells from whole blood. Still today a key reason that diagnostics remains a laboratory‐based activity is the need for centrifugation and fractionation of whole blood with sample sizes of at least 10 mL (about the volume of a large lipstick case). With humans, this requires drawing blood from the arm, uncomfortable and not possible to be repeated numerous times. With small animals used in research, such separations are tedious and certainly require less than 10 mL of blood to avoid killing the animal.Here, we have devised a solution to the true problem of lab‐on‐a‐chip, point‐of‐care diagnostic devices—fluid handling at chip (micro to nano) scales—by using a carefully designed, sterilizable ~40 MHz surface acoustic wave microfluidics handling device that can centrifuge and fractionate whole blood using samples as small as 2 μL. This is a mere pinprick of blood from a human or animal.Acoustic waves transmitted into fluids at frequencies above 5 MHz can generate rapid fluid flows via a combination of compressibility and local fluid motion from the passage of the acoustic wave, but avoid damaging the cells and molecules in the sample as determined via proliferation, QPCR, and mass spectroscopy techniques among other methods. Placing a droplet of whole blood on our device allows it to be spun at over 3000 RPM to cause separation of the particulate components of the blood due to centrifugation and direct interaction of the acoustic wave with those particulates (i.e., the cells). With our unique device, we can furthermore rapidly reverse the rotation of the blood in a few milliseconds, producing an additional means to induce mixing and more finely controlled separation of objects in the blood. The centrifugation completes in ~1 s, about two orders of magnitude quicker than in an ultracentrifuge. After centrifugation, we extract the various components of the blood through microchannels strategically placed to deliver red blood cells, platelets, and other cells separated from each other. These advancements potentially provide an effective platform for whole blood separation and point‐of‐care diagnostics without need for micro or nanoscale fluidic enclosure.Image of 40MHz Omnidirectional spiral surface acoustic wave device with microliter sessile drop on inner circular region. Scale bar: 0.5mm.Figure 1(a) 1.5 μl drop with 3.3μm (red), 5.73μm (green), 43.2μm (green) polystyrene (PS) particles randomly distributed inside. (b) After surface acoustic wave induced separation, showing 3.3μm, 5.73μm, 43.2μm PS particles separated from periphery to center of the droplet. (c) 1.5 μl diluted mouse blood before separation. (d) After surface acoustic wave induced separation, obtaining red blood cells at center and other components of blood at periphery of the drop. Scale bar: 0.5mm.Figure 2