Applications of Biosensors

Pratyush Mishra

BS-MS Second Year

In any biological system there is a natural way of signal transduction. However when the same natural aspects are artificially engineered into a device it becomes a biosensor.

Biosensors are analytical devices which are used for detection of various chemical inputs. These devices are now consequential in many commercial fields, industries and health care aspects

Today, when we are suffering from an ongoing pandemic, early diagnosis is a major challenge. Biosensors are now successfully used for early diagnosis of number of diseases in an effective and efficient manner which ultimately aids the healthcare sector. Several virus detecting biosensors mostly contain graphene as a potential transducing material and many researchers have also developed biosensors for the Zika virus. Similar biosensors can also be explored in the case of SARS-Cov-2.

Apart from the current pandemic that has taken the world by storm, there are two more diseases which have a significant mortality rate and have spread their tentacles all over the globe: diabetes and cancer. We commercially use many blood glucose monitoring devices, most of which rely upon the principle of biosensors. Similarly, use of biosensors can also be expanded as a diagnostic tool for cancer.

Let us take a closer look at the application of biosensors for glucose monitoring and cancer diagnosis.

Glucose monitoring devices

A glucometer is a medical device which can be used to determine the concentration of glucose in blood. Glucose measurements using such devices involve interaction of an analyte which is glucose, and certain glucose specific enzyme like hexokinase (an enzyme which binds to glucose and phosphorylates it), glucose oxidase (GOx) (catalyses oxidation of glucose forming corresponding lactone and hydrogen peroxide) or glucose-1-dehydrogenase (GDH) (a glucose specific enzyme which can oxidize glucose).

Apart from clinical testing, self-monitoring of body glucose (SMBG) is important on a daily basis for diabetic patients in order to maintain their appetite and food habits. The glucose biosensors in these cases generally use two enzyme families: GOx and GDH. These enzymes are highly potent and glucose specific thus, making the device more efficient. The enzyme GOx is generally used because it is cheap and it can withstand extremes of pH and temperature.

Glucometer

Source : Wikimedia Commons By David-i98

The first amperometric (ion detecting) glucose biosensor was developed by Updike and Hicks. In this sensor, a molecule called flavin adenine dinucleotide (FAD) which is attached to the enzyme GOx accepts electron from glucose and get reduced to FADH2(reduced form of FAD).

The FADH2 generated further react with oxygen and releases hydrogen peroxide which is further oxidized near a platinum electrode. The electron lost by this reduction will generate a impulse to be measured. This was a simple first generation biosensing device which used oxygen substrate and detected hydrogen peroxide produced.

The following reactions occur in the sensor which leads to an impulse. Higher the H2O2 or electron produced near the platinum electrode, higher will be the extent of the impulse and accordingly the device will give the reading.

Glucose + GOx − FAD+ → Glucolactone + GOx − FADH2

GOx − FADH2 + O2 → GOx − FAD + H2O2

H2O2 → 2H+ + O2 + 2e-

Due to high cost, high operation potential and oxygen dependence of the first generation glucose biosensor, the 2nd generation of glucose biosensor was developed. It used some sort of redox mediator like ferrocene and ferricyanide to improve the sensor performance. But due to binding competition between the mediator and surrounding oxygen, engineers moved forward to design an another stage of biosensing methodology.

To get rid of all the mediators of electron transfer, the 3rd generation biosensor used direct transfer mechanism of electrons between the enzyme and electrode/transducer where reaction itself gave an electrical impulse.

A blood glucose test strip from Abbott ©

Most of the glucometers used today are based on electrochemical method which is same as the 2ndgeneration glucometer. In this method a test strip contains a capillary which sucks up the required amount of blood in order to give an efficient impulse via the electrode.

However, several non-enzymatic glucose biosensors are now being developed as 4th generation devices. As an alternative to amperometric glucose biosensor, fluorescent glucose biosensor is now widely used especially for continuous glucose monitoring.

Cancer diagnosis

In case of cancer the analyte used is generally a tumor biomarker like prostate specific antigen (PSA), cancer antigen 125, CA 15-3 etc. Different cancers will have different biomarkers thus would involve different biosensing methodology. So by measuring levels of such kind of analytes secreted by the cancerous/tumor cells biosensors can detect whether a tumor is present and whether it is malignant. Biosensors for cancer should have a potential to detect multiple analytes since most types of cancer involve more than one biomarker.

Prostate specific antigen (PSA) recognizing biosensors generally use an anti-PSA antibody for their detection. Moreover amperometry based biosensors can also be used in cancer diagnosis in which they utilize sequence specific DNA sequences as a recognition element. These sensors rely on gene mutations associated with a specific cancer-causing DNA based hybridization of it with the sequence specific recognition element. There are several new methods that are now currently developed to detect specific cancer by engineering cost effective biosensors.

Development of biosensors depends entirely on the field of application which include biotechnology industries, agriculture, food technology and medicine/health care.

Health being a primary concern, requires development of several diagnostic tools. Although we mentioned the application of such devices in checking hyperglycemia and detecting cancer, there are vast number of applications of this technology and many researchers are still working on it to develop more efficient sensors that could be used in healthcare sector.

We will highlight more applications of biosensors in upcoming issues.