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Publication Date: 2013-Jan-18
Document File: 5 page(s) / 351K

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Commercial glucose sensors for diabetics are adapted to monitor glucose levels in bioreactors.

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Commercial glucose sensors for diabetics are adapted to monitor glucose levels in bioreactors.


In cell culture, the most common method to monitor glucose levels is to analyse glucose via testing a sample of fluid that is withdrawn from the culture. However, this creates challenges related to sterility. Noninvasive methods include optical methods, such as trying to undertake Raman analysis. Those methods require, however, that optical ports be added to the bioreactor, which typically is a single use bioreactor. Other methods include localising enzyme based sensors in the bioreactor, but they must then be able to withstand the gamma or other sterilisation methods used to sterilise the bioreactor. In addition they must not leach enzymes or other materials into the reactor.

There is therefore a need of novel methods to follow glucose levels in cell culture, especially methods that can be applied to single use bioreactors and allow for non-invasive means to monitor glucose in order to allow for maintenance of sterility.

US 2010/0129899 A1 discloses a flexible bioreactor wherein parts of the flexible bottom wall are interrupted by at least one rigid element comprising measuring means allowing for non- invasive monitoring of cellular activity in the bioreactor when in use. The rigid element may be a dialysis membrane or a filter membrane with a selected pore size. Analytes that may be measured include carbohydrates (e.g. glucose), organic acids (e.g. lactic acid) and peptides, as well as gaseous O2 and CO2.

Summary of the invention

According to the invention, it is suggested that methods used to follow glucose levels in diabetic patients be adapted to glucose measurement in cell culture, and more specifically methods that are non- or minimally-invasive.

In one exemplary embodiment, the use of iontophoresis to draw samples across the skin, e.g. as in the commercially available GlucoWatch sensor for diabetic patients, is adapted to draw

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samples through a bioreactor bag film, more specifically across a dialysis membrane or similar patch provided in the bioreactor bag wall.

In another exemplary embodiment, sample wires are embedded in part of the tie-layer of a single use bioreactor, such as in the commercial Dexcom Plus Seven sensor for blood glucose measurements.

A glucose sensor according to the invention will work like a normal enzymatic based glucose sensor, but the problem of maintaining sterility is solved by having a membrane that only allows some fluid and small MW solutes like glucose to be transmitted and only under controlled conditions.

Detailed description of the invention

As mentioned above, the invention resides in adapting commercial glucose sensors for diabetics to monitor glucose levels in bioreactors.

First embodiment

In one embodiment, the glucose sensor is based on iontophoresis technology. Iontophoresis involves the application o...