Bio Sensors and Lab on a chip

Question 1

Define biosensor

Answer 1

A sensor that integrates a biological element with a physico-chemical transducer to produce an electronic signal proportional to a single analyte which is then conveyed to a detector

Question 2

What do you need to consider when building a biosensor

Answer 2

• The analyte
• The sample handling
• Detection/recognition
• Signal- how do tou

Question 3

What is the analyte

Answer 3

What you want the biosensor to detect

Question 4

What do we mean by the sample handling of a biosensor

Answer 4

How it is going to deliver the analyte to the sensitive region

Question 5

What do we mean by the detection/recognition of a biosensor

Answer 5

How does the biosensor specifically recognise the analyte

Question 6

What is the signal?

Answer 6

This needs to be a specific signal from a specific binding
If there is non specific binding and interface. False recognition can distort the result leading to false positives and negatives

Question 7

What are the essential characteristics of a biosensor ?

Answer 7

Linearity- The sensor should have a linear response to the concentration of the substrate
Sensitivity - This is the value of the electrode response per substrate concentration
Selectivity - The chemical interface must be minimised for obtaining the correct result
Response time - This is the time necessary for having 95% of the response - want this to be short

Question 8

When was the first modern biosensor made?

Answer 8

1962 by prof leland clark

Question 9

What are the two most common biosensors ?

Answer 9

Pregnancy tests

Glucose tests

Question 10

What does a pregnancy test test for ?

Answer 10

Human chorionic gonadotrophin (hCG)

This is an enzyme which increases in concentration post conception and during foetal growth and is detected in the urine

Question 11

What chemical reaction occurs on a pregnancy test?

Answer 11

Monoclonal antibodies which only bind to this enzyme have been developed
- They work because the anti-alpha-hCG binds to the alpha domain and the anti-beta-hCG binds to the beta domain on the hCG
The Fc end of the enzyme is bound to activate dye in the catch region
The process by which it studies these enzymes is ELISA (enzyme linked immunosorbent assay)

Question 12

What physical interaction occurs in a pregnancy test

Answer 12

The test uses a hydrophillic wicking strip
The enzyme labelled reporter antibodies bind to the hCG and travel to the catcher region where antibodies are covalently bound.
the hCG binds to the catcher region and the colour is generated by the enzymatic activation of dye.

Question 13

What are glucose tests used for

Answer 13

Used by diabetics as frequent glucose monitoring has been shown to mean significantly fewer diabetes related complications to their health as tighter control on blood sugar levels

Question 14

What hormones are responsible for blood sugar levels and where are they produced

Answer 14

The pancreas produces insulin and glucagon

Question 15

1st Generation glucose measuring device

Answer 15

measures directly H2O2 and depends on O2 and H2O2 levels

Question 16

2nd Generation glucose measuring device

Answer 16

This is a mediated biosensor - It uses ferrocene independent from oxygen pressure –> This means it has lower redox potential

Question 17

3rd Generation glucose measuring device

Answer 17

Mediatorless- looks at direct electron transfer

Question 18

Early examples of glucose detection

Answer 18

One of the earliest diagnostic methods involved a uroscopy where sugar is present when it shouldn’t be.

Question 19

Define microfluidics

Answer 19

Devices that control liquids constrained at volumes in the micro litre range- exploiting the flow behaviour in this length scale

Question 20

Why do we use microfluidics in biosensing

Answer 20

Microfluidics are used because you can use smaller sample volumes with high concentrations of analyte - this makes it easier to detect at low compound concentrations

Question 21

What materials are biosensors made out of

Answer 21

Often made from glass and perspex which under goes eplication with silicone to form PDMA- This is easily made into moulds of patterned surfaces

Question 22

Properties of microfluidics

Answer 22

• Experiences laminar flow - there is no mixing of fluids or diffusion so need to manually mix
• Fast thermal relaxation (estimating the time required for heat to conduct away from a directly-heated tissue region)
• Surface tension is one of the main forces acting on the fluid

Question 23

What two ways can we mix fluids in a biosensor. What do these overcome

Answer 23

T junction fluidic mixers
Chaotic mixers

These overcome the laminar flow nature of the fluid and enable us to mix fluids

Question 24

Give some examples of lab on a chip devices

Answer 24

Biochemical assays
Chemical applications
Biological application

Question 25

What do Biochemical assays lab on a chip devices do

Answer 25

• These can carry out real time PCRs (making copes of DNA sequences)
• Carry out immunoassays
• Can do dielectrophoresis for detecting cancer cells and bacteria

Question 26

What do chemical application lab on a chip devices do

Answer 26

• Sperate molecules from mixtures
• Chemical reactors
• Chemical detection

Question 27

What do biological application lab on a chip devices do

Answer 27

• Cell coculture
• Biosensors
• Drug screening
• Single cell analysis

Question 28

Give an example of a microfluidic diagnostic method

Answer 28

Portable point of care (POC) medical diagnostic system

Question 29

Aim of POC medical diagnostic systems

Answer 29

• Inexpensive
• Accurate
• Reliable
• Suited well to medical conditions in developing countries

Question 30

What is the aim of building and animal/human on a chip

Answer 30

To get rid of the need for animal testing
Mimics the bodies physiology on a miniature scale
Seen to be accurate but not yet perfect

Question 31

Why do we need a chip of the whole body not just individual tissues

Answer 31

The human body is a complex environment

Drugs get transformed in the body by different parts in different ways

Question 32

The lab on the chips aims to put drugs in an environment where

Answer 32

• We can co-culture different cells
• The cells are in a bio mimetic environment
• Mechanical cues are included in the tissues environment

Question 33

Liver on a chip

Answer 33

• A highly porous membrane is used to mimic the endothelial barrier and then the device is back filled with hepatocytes

The liver receives blood flow from the hepatic artery and the portal vein
This carries xenobiotics such as ingested drugs from the small intestine to be metabolized by liver
hepatocytes.
Low pressure blood flow travelsfrom branches of the hepatic arteries and hepatic portal vein through the liver sinusoids and drains out via the central vein.
The hepatocytes reside in thin cords and form extensive cell-cell contacts. The sinusoid space is
bordered by a sheet of endothelial cells which lack a basement membrane (highly permeable).

Question 34

Lung on a chip

Answer 34

Attempts to improve live models of the alveolar capillary barrier
During inhalation contraction of the diaphragm causes reduction in intrapleural pressure which leads to distention in the alveoli and stretching of the alveolar capillary interface
A PDMS based lung mimic is used- vacuum on side channels which makes the membrane stretch