Technologies

Acoustic sorting of biological cells


Abstract/Technology Overview

Cell sorting is used to identify, count and extract specific target cells from a generic population, such as blood for disease diagnosis or cell cultures for tissue engineering. Typically, target cells are fluorescently labelled and detected via laser excitation. Current methods are inefficient, missing some target cells and causing significant cell death - often only half the target cells are collected alive. This technology brings cells along a microfluidic conveyor belt in single file, interrogates them with a laser and selects target cells using a highly focused acoustic wave to push the target cell to the desired output of the microfluidic device, capable of collecting 98% of target cells with almost 100% viability. 

The core technology is an acoustic chip with associated microfluidics, that can be integrated with conventional optical cell detection systems. 


Technology Features, Specifications and Advantages

At the heart of this technology is an acoustic chip that produces an acoustic beam in a microfluidic device that measured just a few tens of micrometers across. The acoustic chip comprises a curved transducer on a piezoelectric material to focus a surface acoustic wave to a narrow beam, which couples into a contacting microfluidic device. This acoustic beam gently displaces micron-sized particles in its path; triggering this beam only when a target object is identified provides a highly selective sorting method. 

Current cell sorters, or flow cytometers, encapsulate cells into aqueous droplets and droplets containing target cells are charged so that they are deflected into the desired outlet container using an electric field. Both depressurisation during droplet formation and the electric field compromise cell health, resulting in significant mortality for sensitive cells, such as stem cells. This acoustic technology avoids these harmful effects and provides a more efficient and gentle cell sorting that is suitable for fragile cells.

Laboratory tests have demonstrated sorting rates of 4,000 events per second with 98% of MCF-7 (breast cancer) cells collected from spiked whole blood, which presented almost 100% viability after sorting. In conventional flow cytometry, it is expected that around 50% of target cells will be lost. 


Potential Applications

This technology can be applied to sorting any micron-sized particles in suspension, and we have identified two key areas where this technology could be disruptive.

The first is sorting biological cells that cannot be sorted using conventional flow cytometers, such as stem cells. As such, this is a generic cell sorting platform that would find use in academic and industrial research laboratories, clinical research centres and hospitals. 

Stem cell therapies attracted over USD$4B in private funding in 2017, and there were over 100 potential therapies in clinical trials in 2016; stem cell sorting is a key capability for meeting the future needs of the stem cell therapy industry. The global cell sorting and isolation market was valued at USD$3.6B in 2016, yet most existing flow cytometers do not meet the needs of the stem cell therapy market. 

The second application is liquid biopsy for early cancer diagnosis, where circulating tumour cells are identified and extracted from whole blood, allowing further pathological studies for diagnosis and treatment planning. 

Whilst these applications are healthcare related, the core technology can sort any micro-particulate matter from liquid samples that can be identified with a fluorescent label.

 


Customer Benefit

For generic cell sorting, this technology offers the following benefits to end users:

1) Easier set-up with fewer parameters than conventional flow-cytometry
2) No droplet formation or electric fields that are harmful to cells
3) Unparalleled recovery of target cells 
4) Gentle sorting with no significant adverse effects on cell viability
5) Smaller device footprint (approximately 1 square foot) than conventional flow cytometers
6) No aerosol generation

OVERVIEW
Technology Owner

Kok Yong Tan

Company

Singapore University of Technology and Design

Technology Category
  • Medical Devices
Technology Status
  • Available for Licensing
Technology Readiness Level
  • TRL 5
Keywords

Medical device, Cell sorting, Cell sorter, Diagnostics, Acoustic, Cytometry, Single cell, Single cell analysis