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Step-change in antibody discovery process

7th October 2019


Advances in medical diagnosis and treatment are constantly evolving but developing a new procedure into a commercial, scalable process can be a lengthy and challenging journey. Bürkert Fluid Control Systems has applied its expertise in microfluidics to deliver a crucial component that will enable antibody biotherapeutics to be identified and isolated much more efficiently.

Cambridge is a centre for Life Sciences and creation of new biotechnology in the UK. Sphere Fluidics is one of a few companies involved in advanced research and development and, as an innovator in technology, its role is to convert theory into reality. To do this, they enlisted the help of a company that specialises in biomedical engineering, The Technology Partnership (TTP), to make a microfluidic prototype into a commercial product.

Innovative solutions

Bürkert has often worked with TTP, which acts as a scientific consultant and locates resources for various companies to develop their technology and build it on a commercial scale. Bürkert has been providing innovative solutions to challenges that development teams face, offering expert engineering advice in fluid control, especially in microfluidic and hygiene applications.

Antibody-based therapeutics are fast becoming a major class of modern medicine especially for the treatment of cancer and autoimmune disorders. However, traditional methods for screening large panels of cells used in antibody discovery during lead selection is a very time-consuming, expensive and inefficient process.

Until recently, manual or semi-automated technologies, such as cell sorting, colony picking, and cell-in-well imagers have been used to screen and isolate rare cells secreting antigen-specific antibodies. These antigen-specific antibodies can be used to target a specific antigen that is known to be present or as a diagnostic tool that will react with the antigen if it is present.

Developing new technologies

Sphere Fluidics has developed a process that can isolate single cells for analysis and characterisation. More specifically, a process that selectively isolates rare antigen-specific B cell and hybridoma clones from large starting populations. Using proprietary microfluidic picodroplet technology, the process compartmentalises cells into individual aqueous picolitre volume compartments (called picodroplets) in an oil emulsion.

The process of creating picodroplets involves encapsulating a single cell, which is contained in an aqueous solution, in a spacer fluid which is a proprietary, fluorinated oil that is immiscible with the fluid surrounding the cell. Specialised biocompatible surfactants stabilise these picodroplets to prevent subsequent aqueous / oil layer separation. This posed two major issues when it came to creating a commercial solution for this technology: The control valve dispensing the spacer fluid needed to have very fast opening and closing times and the seals needed to be compatible with the carrier oil.

The cell concentration within the aqueous solution dictates the number of cells that are encapsulated in each picodroplet. Each one is then analysed and sorted and only those containing a single cell producing antigen-specific antibodies will be collected into wells of microplates.

Finding the right components

Based on the flow and size of picodroplet that was needed, Sphere Fluidics calculated the speed and volume required from the valve. Until this point, the company had been unable to find a valve that would deliver the speed and the chemical resistance that was required.

As a specialist in fluid control systems, especially microfluidics, Bürkert was approached by TTP for a high frequency control valve that had a very small dead volume and was compatible with the above fluorinated oil. Emmett O'Sullivan at Bürkert, explains: "We offered the Type 6712 Whisper valve because it seemed ideally suited to this application. It is designed for desktop apparatus, has a switching frequency of 50Hz, and a switching noise of less than 36 dB."

The Bürkert valve was trialled for two weeks, and in this time it was quickly established that the valve was the ideal solution. Following further consultation, the project to build the commercial benchtop analysis system was given the go-ahead. The Cyto-Mine Single Cell Analysis System is the first instrument of its kind, being able to analyse, sort and dispense millions of individual cells in just a single day.

As a result, the Cyto-Mine has already become a commercial success, offering huge improvements in speed and productivity for the discovery and development of biotherapeutics.





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