Question

1. In relation to these clinically important analytes, answer the following questions.

Analytes: H + Ca2+ K + Glucose Lactate Urea Ethanol Glycerol O2 Dopamine Serotonin Glutamate Cortisol Acetylcholine

b) For each “type” of analyte, answer the following. How can you go from "biorecognition" of the analyte in a sample to "detection"? What is the matrix that your sample resides in (blood, urine, tissue, etc.)? How will you collect the biofluid or access the analyte? Will the wearable sensor perform an in vitro analysis or will you detect continuously in vivo? How fast does your sensor need to respond? What is the limit of detection required? (***HINT: You should be able to group the analytes together based on biorecognition element/sensor type. Are there processes associated with this analyte that might make it have concentrations that are rapidly changing?)

c) For 2 of the “type” of analyte suggest a sensor design keeping the above points in mind and including the following information. a. Which class of transducer will you use? b. How will you couple the bio-recognition element to the transducer? c. What signal will you have to design the electronics to measure?

d) Where and how can the device be integrated onto/into the wearer? What are some considerations for the devices location?

Answer 1

Biorecognition is the biological identification of specific compounds

H ⁺ Ca²⁺ K ⁺ : Ion selective electrode or potentiometric biosensors can be used for the detection of such analytes.

Glucose, Lactate, Urea, Glutamate, Cortisol, Acetylcholine: all these can be biorecognise using enzyme based biosensors like enzyme electrode is used for detection of glucose.

Ethanol, Glycerol, O_2, : Microbial biosensors can be used for detection of such analytes

Dopamine, Serotonin: Surface Plasmon resonance biosensor can be employed for detection of these analtes

The sample mostly resides in the blood either in plasma or serum and urine Biofluid mainly collected through needle or microneedle technique, or tthrough body ejected fluids such as urine, saliva, intestinal fluid or tear fluid. Wearable sensor enable continuous monitoring of metabolites. These sensors must respond quickly and should have ultra-high sensitivity.

c) There are three main parts of a biosensor: (i) the biological recognition elements that differentiate the target molecules in the presence of various chemicals, (ii) a transducer that converts the biorecognition event into a measurable signal, and (iii) a signal processing system that converts the signal into a readable form. The molecular recognition elements include receptors, enzymes, antibodies, nucleic acids, microorganisms and lectins.

The basic concept of the glucose biosensor is based on the fact that the immobilized GOx catalyzes the oxidation of β-D-glucose by molecular oxygen producing gluconic acid and hydrogen peroxide [35]. In order to work as a catalyst, GOx requires a redox cofactor—flavin adenine dinucleotide (FAD). FAD works as the initial electron acceptor and is reduced to FADH2.

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

The cofactor is regenerated by reacting with oxygen, leading to the formation of hydrogen peroxides.

GOx − FADH2 + O2 → GOx − FAD + H2 O2

Hydrogen peroxide is oxidized at a catalytic, classically platinum (Pt) anode. The electrode easily recognizes the number of electron transfers, and this electron flow is proportional to the number of glucose molecules present in blood.

The transducer used is electrochemical type.

Potentiometric biosensors make use of ion-selective electrodes in order to transduce the biological reaction into an electrical signal. In the simplest terms this consists of an immobilised enzyme membrane surrounding the probe from a pH-meter, where the catalysed reaction generates or absorbs hydrogen ions. The reaction occurring next to the thin sensing glass membrane causes a change in pH which may be read directly from the pH-meter's display. Typical of the use of such electrodes is that the electrical potential is determined at very high impedance allowing effectively zero current flow and causing no interference with the reaction.

d) These wearable biosensors can be integrated in the body, such as the trunk, leg, arm, etc.