BLOOD GLUCOSE TEST STRIPS - Problems and fixes!! PART III

Methods of electrochemical analysis

All EBGTS (Electrochemical blood glucose test strips) produce a time varying current  which must be analyzed to deduce a glucose concentration. 
However, the method of analysis varies substantially, depending upon the strip design. 
In the broadest sense, the analysis can be either 
1. amperometric, in which the instantaneous current at a particular time is proportional to glucose, or 
2. coulometric, in which the integrated charge underneath the entire curve is proportional to glucose.


Amperometric strips predominate among electrochemical test strips. Typically the current is measured 5-15 seconds after the strip is filled with blood, and that current level is directly proportional to the glucose concentration. There are, however, many variations on this theme. For example:

1. Current can be measured and averaged over a short (a few seconds) interval.
2. Peak current can be measured.
3. A mathematical analysis of the declining portion of the current-time curve (termed a Cottrell analysis) can be performed.

In general, strips designed for amperometric analysis share some features:

1. The surface area and surface roughness of the working electrode must be highly reproducible to insure that current-time curves are reproducible from strip to strip.
2. The electrode surface-area/sample-volume ratio is low, so that glucose is not substantially depleted in the strip during the analysis.

 Enzymes used in the strips

Table I. Commonly used enzymes for EBGTS
Enzyme	Reacts with O2?	Reacts with maltose?
Glucose Oxidase	Yes	No
PQQ-Glucose Dehydrogenase	No	Yes
NAD-Glucose Dehydrogenase	No	No
FAD-Glucose Dehydrogenase	No	No

Four enzymes are commonly used in these strips






Glucose oxidase was first employed in EBGTS, and is still used in a few commercially available test strips, although its use is declining, since it reacts rapidly with oxygen. EBGTS made with glucose oxidase produce currents that are dependent on the amount of dissolved oxygen in the blood sample, which is heavily dependent on the hematocrit (% red blood cells) in the sample.
Glucose oxidase has been largely supplanted by the dehydrogenases, which do not react appreciably with oxygen. (In the table above: PQQ, NAD, and FAD refer to the electron transferring cofactors, which differ between each of the distinct enzymes.) However PQQ-GDH does react with many non-glucose sugars, particularly maltose, which can be elevated in patients undergoing peritoneal dialysis. For this reason, use of PQQ-GDH is decreasing, and the FDA has recently restricted its use in new commercial products.
Both NAD-GDH and FAD-GDH combine oxygen rejection with high specificity for glucose. Their use in EBGTS is increasing. Enzymes typically are deposited on at least the working electrode, and sometimes on one entire side of the sample chamber, and are codeposited with buffers and stabilizing agents, such as bovine serum albumin.

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BLOOD GLUCOSE TEST STRIPS - PART II - The EBGTS story!

Electrochemical blood glucose test strips (EBGTS)

The electrochemical blood glucose test strip (EBGTS) is a very small volume (often about one µl or less) disposable electrochemical cell, which is contacted with whole blood. It then produces, in conjunction with a test meter, an electrical current which is proportional to the blood glucose concentration. Typical currents are a few µA.

This electrical current is produced by the very selective oxidation of glucose in the blood sample, which is catalyzed by two reagents which are precoated inside the test strip: 

(i) an enzyme, which reacts directly with the glucose molecule to remove its two available electrons, and 

(ii) a mediator molecule, which takes (either singly or as a pair) the two electrons from the enzyme, and transports them to the working electrode, where they can be measured. 

This process is illustrated in Figure below.

Electrons flow from glucose to an enzyme to a redox mediator to the working electrode.


The enzyme and mediator act as a sort of electron bucket brigade to transport electrons from glucose to the working electrode. Each enzyme and mediator molecule can repeat this transfer again and again, if necessary. There are a wide variety of different enzymes and mediators which are suitable for use in an EBGTS. Although there are many differences between the various commercially available test strips, they all rely on the fundamental mechanism 


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BLOOD GLUCOSE TEST STRIPS - How do they work? PART I

1. Insert a disposable test strip into the meter, automatically turning the meter on.
2. Lance the skin with a fine sharp to produce a small blood droplet, about one mm in diameter (volume = 0.3 to 5 µl)
3. Sample the blood with the test strip, attached to the meter.
4. The meter interrogates the strip in order to measure the blood glucose concentration, typically requiring about 5-10 seconds.

The test strips described in the above procedure can be either optical, in which glucose-derived electrons effect a change in the color of an indicating dye molecule, or electrochemical, in which case the glucose-derived electrons are routed directly through the external meter, and counted. For various reasons, including accuracy and the ability to measure extremely small blood volumes, electrochemical strips have gained the advantage in recent years, and now comprise a growing majority of the test strip market.

Components of a test strip

Automatic coding

Generally, calibration codes, corresponding to a particular batch of strips, are entered into the meter by the user, either manually or through insertion of a calibration “chip,” that accompanies the strip vial. However, it is desirable to entirely bypass this process, since user error is always a possibility. Therefore, some EBGTS do not require calibration of any sort. This is generally accomplished by:

1. Precise manufacturing control of the sensitivity of the produced strips, such that their performance is highly reproducible from batch to batch. In this process, strips are rejected, and disposed of, if their performance does not meet very stringent performance criteria.
2. Adding an indicating mark to the strip that the meter can use to assign a calibration code.

Both systems are currently in use, and automatically coded strips make up an increasing share of EBGTS

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Tomorrow we will discuss about the Electrochemical blood glucose test strips (EBGTS) - The newest and commonest type of strips used today