Nano Does a Mega Tango: FETs To Change The Fate Of Diabetics

The role of electronics in medicine or physiology is a very important one. Ranging from CT scan, fMRI, PET scan or electron microscopes and a variety of other medical investigations, medical science depends on electronics and its allied disciplines.

A simple illustration is as follows. Everyone knows that the estimation of blood glucose is the cornerstone in the diagnosis and therapy of diabetes mellitus and other hyperglycemic illnesses such as hyperthyroidism, hyperpituitarism and others. Even hypoglycemic ailments (conditions where the blood glucose levels are less than normal) like hypothyroidism, hypopituitarism or hyperinsulinemia, hypoadrenocorticism need the estimation or quantitation (quantification) of blood glucose, in order to clinch their diagnosis.

Glucose may be estimated in the blood in a variety of methods. One of the easiest methods rely on the simple reaction of glucose with potassium per-manganate. Glucose is a reducing monosachharide; while potassium permanganate is a strong oxidizing agent, so much so that it produces frank fire when added to glycerine not to mention of its emanation of oxygen (O2) when heated. When KMnO4 (potassium permanganate) is added to glucose, it (KMnO4) is reduced to manganese ions (Mn++). The colour changes from purple pink to colorless. This can be seen by the naked eye, giving us an estimate of the amount of total glucose that is present.

Another approach that is adopted nowadays is the enzymatic oxidation of glucose and their quantitation thereof. Here enzyme glucose oxidase (GOD) is used to oxidize glucose to D-gluconic acid and hydrogen peroxide (H2O2). In the presence of H2O2, hydrogen peroxidase (POD) oxidizes phenol, which combines with 4-amino antipyrine to form a red dye (quinone imine). The intensity of the red dye is linearly proportional (upto 500 mg% i.e. 500 mg per dl) to the glucose concentration in the specimen. The intensity of the color that is formed is measured by using a colorimeter; a device that measures the transmittivity of light (through the liquid) by employing LDR (Light Dependent Resistor) or phototransistors or similar devices.

Recently, advances in nanotechnology and nanoscience as a whole, is offering a brand new hope of determining blood glucose within the patients blood itself. That is you don't need to prick the guy. They are using a device called ISFET (Ion Sensitive Field Effect Transistor). It is variant of FET devices (a picture of a MOSFET i.e metal oxide semiconductor FET, is shown on the left). In a ordinary bipolar transistor, we forward bias the emitter-base junction by applying a current and make the collector strongly reverse biased. Thus any input current in the base emitter circuit is amplified several times when the electrons 'rushes' towards the attracting collector. A FET also works in much the same way. The difference is that the flow of charge carriers are controlled by a electric field applied in the Gate (G) Source (S) junction. This electric field is generated by a voltage: VGS. Thus while bipolar junction transistors (BJT) are current controlled, the FET devices are voltage controlled.

Recently, a team of physicists led by Raj Mohanty from Boston University has made a nanoscale glucose sensor using ISFETs and nanowires consisting of silicon. The silicon nanowires were primed with glucose oxidase on their surfaces and these nanowires bridged the source and the drain electrode of the MOS device. The conductivity of the 'wire' would change depending upon the glucose concentration in blood as it is reacted upon by the enzyme present on its surface. A voltage drop will ensue between the source and the drain electrodes, which may be read and interpreted by a voltage comparator. The researchers claimed that these could be put in vivo with virtually no risk. Humans do have the habit of carrying silicon on their bodies and that hardly do them any harm! We may be able to noninvasively monitor the blood glucose of diabetic persons, may even be able to act upon it, by incorporating a feedback circuit that would actuate an insulin pump, in times of hyperglycemia.

Of Mighty Mice and Men

In my article, Doping: To dope or not to dope, I mentioned how athletes exploit the pharmaceutical and other abilities of drugs to manipulate things in their favor. Trained athletes learn to use fatty acids as energy source more effectively than untrained men, over time. Burning fatty acids as fuel has the advantage of not producing lactate, metabolites of carbohydrates that is the cause of muscle cramps. At the same time, lactate, being acidic in nature, inhibit vital enzymes necessary for tissue reactions. Trained (and trendy) athletes who are experienced, overfeed themselves with carbohydrates days prior to a sporting event. This produces ample glycogen stores in them which come handy during the event as energy source.

But it seems that the mouse is going to beat them at their own turf! I am not talking about your brand new electronic optical (or bluetooth) mouse, I refer to our own natural rodent. It is well known that scientists have a penchant for using mice as experimental guinea pigs for their research. In this process they have produced "brainbow" in mice, a multicolored novel approach to explore neural networking; given birth to fearless breed of mice-no longer afraid of cats, by ablating their olfactory (smell) neurones and doing away with their smell associated identification of their enemies etc.

Now scientists have inserted a gene into mice that has made them far more stronger, hardier and has more stamina. This research was led by Richard Hanson, professor of biochemistry at Case Western Reserve University at Cleveland, Ohio. He first made a cDNA (complimentary DNA) of the enzyme PEPCK-C (phosphoenol pyruvate carboxykinase). Creating a cDNA may be compared to making a rubber stamp (or the negative of a photograph) which when inserted into the DNA sequence will keep on 'stamping', creating more proteins (enzymes) in the process. PEPCK-C cDNA was then linked to the skeletal actin gene promoter (a promoter may be conceived as a DNA sequence that instructs a gene to transcribe). Thus PEPCK-C was produced along with actin and the "mighty mouse" emerged. The PEPCK-C gene is expressed in the liver, kidney and some other tissues. This enzyme plays vital role in both carbohydrate and lipid metabolism, the transgenic mice that were produced was very efficient in utilizing fatty acids as energy source.

Cause for concern? Well, I can't envisage a mouse brigade in the near future.