Acoustic Trapping in Biomedical Research

Sammanfattning: Herein a method that uses acoustically resonating glass capillaries and enables non-contact capture of micron-sized bioparticles, i.e. acoustic trapping, is described. A miniaturized ultrasonic transducer is used to locally actuate a cross-sectional resonance in the capillary. A 2000×200 µm2 capillary is typically operated around a resonance frequency of 4-MHz. Optimal design of the transducer for this purpose is investigated in detail, showing that mode-control in the transducer results in a more efficient device, and makes automatic frequency tracking possible. A system design that allows easy assembly and disassembly of the transducer and the capillary also demonstrates how a single-use device can be accomplished. A breakthrough for the presented acoustic trapping technology is the introduction of seed-particles. These enable trapping of submicron particles that would otherwise be impossible to capture in this kind of system. It is shown how controlled interaction with the larger seed particles can circumvent this limitation. Using this approach capture of 110 nm particles and Escherichia coli bacteria is demonstrated with 95% capture efficiency. The usefulness of the acoustic trapping device in biomedical research is demonstrated in applications such as; efficient washing of functionalised beads for biomarker detection in blood plasma, dynamic studies of cell-drug interactions, and purification and identification of microbes from infected blood. To enable these applications the acoustic trap an interface to a Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) instrument has been devised. This is facilitated by designing the acoustic trap to operate in aspirate/dispense mode (like a pipette) depositing liquids in a microchip for solid phase extraction and subsequent MALDI MS analysis. Tracking and logging the system resonance frequency provides a new way to measure the amount of captured material as well as continuously adjusting the driving frequency to changes in the infused samples. Apart from providing a new measurement method, continuously adapting the resonance frequency enables samples with a wider range of acoustic properties to be processed. This is demonstrated in an assay for bacteria typing with MALDI MS in blood cultures. Here, acoustic trapping provides a faster and more automatable sample preparation method as compared to the one currently used in the clinical assay.