Biosensors and Microsystems L11-18 Flashcards
1
Q
Define a biosensor.
A
A biosensor is a chemical sensing device in which a biologically derived recognition entity is coupled to a transducer, to allow quantitative or qualitative analysis in a complex biochemical matrix.
2
Q
Biosensors incorporate a specific ____1____ element (that creates a recognition event) and a ____2____ element (that converts the recognition event into a recordable signal).
A
- Biological
- Physical
3
Q
Basic Principle of a Biosensor
A
4
Q
Coupling the biorecognition element to a transducer can be achieved in four ways. State each.
A
- Membrane Entrapment
- Physical Adsorption
- Porous Entrapment
- Covalent Bonding
5
Q
Define analyte.
A
A substance or chemical constituent that is of interest in an analytical procedure.
6
Q
What characteristics must biosensors exhibit? (4)
A
- Repeatability – Intra-assay variability
- Reproducibility – Inter-assay variability
- Specificity/selectivity (to analyte of interest)
- Sensitivity – Linear range, detection limit, response time
7
Q
Resonance Based Biosensors
In resonant biosensors, a light-wave ____1____ is coupled with an antibody, or bioelement.
When the analyte molecule, or antigen, gets attached to the membrane, the ____2____ of the membrane changes (due to surface flexing).
The resulting change in the mass subsequently changes the resonant frequency of the ____1____ (light hits somewhere else).
This frequency change is then measured.
The degree of flexion = ____3____ of antigen.
A
- Transducer
- Mass
- Concentration
8
Q
Thermal Detection Biosensors
Exploits the absorption or production of heat, that in turn changes the ____1____ of the medium in which the reaction takes place.
Predominantly enzyme based.
When the analyte comes in contact with the enzyme, the energy change of the enzyme reaction is measured and calibrated against the analyte ____2____.
The total heat produced or absorbed is ____3____ to the total number of molecules in the reaction.
Common applications of this type of biosensor include the detection of pesticides and pathogenic bacteria.
A
- Temperature
- Concentration
- Proportional
9
Q
Ion-Selective Field Effect Transistors (ISFET)
Ion sensitive biosensors are semiconductor FETs having an ion-sensitive surface.
The surface electrical ____1____ changes when the ions and the semiconductor interact.
This change in the ____1____ can be subsequently measured.
The ISFET can be constructed by covering the sensor electrode with a polymer layer.
This polymer layer is ____2____ permeable to analyte ions.
The ions diffuse through the polymer layer, causing a change in the FET surface ____1____.
This type of biosensor is primarily used for ____3____ detection.
A
- Potential
- Selectively
- pH
10
Q
Electrochemical Biosensors
The underlying principle for this class of biosensors is that many chemical reactions produce or consume ions or electrons, causing some change in the electrical properties of the solution that can be used as a measuring parameter.
Electrochemical biosensors can be classified into 3 types, based on measured electrical parameters.
What are they? (name + parameter)
A
- Conductometric - measures conductance
- Potentiometric - measures changes in potential difference
- Amperometric - measures current
11
Q
Conductance = inverse of ______
A
Resistance
12
Q
Ohm’s Law deals with the relationship between voltage and current. This relationship states what?
A
The potential difference (voltage) across an ideal conductor is directly proportional to the current through it.
13
Q
State the equation for Ohm’s law.
Include key.
A
V = I R
where:
V is the potential difference between two points
I is the current flowing through the resistance.
R is the resistance to current flow
14
Q
Conductometric Biosensors
Based on measuring changes in ____1____ of a selective material.
Since the inverse of resistivity is conductivity, these sensors are interchangeably called conductometric sensors or chemiresistors.
There are two types of these sensors:
- A selective material, which can change its conductivity upon interaction with chemical species is clamped between two contact electrodes and the ____1____ of the entire device is measured. Used in____2____ sensing.
- The chemically interactive layer is at the top of an electrode, which is immersed in the solution of ____3____. Used in biosensing
A
- Resistance
- Gas
- Electrolyte
15
Q
Potentiometric biosensors make use of ion-selective electrodes in order to ____1____ the biological reaction into an electrical signal.
This consists of an immobilised enzyme membrane surrounding the probe from a pH-meter where the catalysed reaction
generates or absorbs ____2____ ions.
The reaction occurring next to the thin sensing glass membrane
causes a ____3____ in pH.
A
- Transduce
- Hydrogen
- Change
16
Q
An amperometric biosensor is a high ____1____ biosensor that can detect electroactive species present in biological test samples.
Since the biological test samples may not be intrinsically
electroactive, enzymes are needed to ____2____ the
production of reactive species.
In this case, the measured parameter is current.
A
- Sensitivity
- Catalyze
17
Q
Name the 2 major areas of commerical success for biosensors.
A
- Diabetes monitoring (blood glucose measuring)
- ClearBlue® (pregnancy test)
18
Q
Blood glucose biosensors account for approximately 85% of the current world market for biosensors (~£2.5billion)
What is the reasons why the glucose market was particularly receptive to the introduction of biosensors?
A
The high (and increasing) prevalence of diabetes in developed nations.
19
Q
Most enzyme biosensors (glucose included) rely on ______ enzymes.
A
Redox
20
Q
The most commonly used enzymes in the design of glucose biosensors contain redox groups that change redox state during the biochemical reaction.
Enzymes of this type are glucose ____1____ (GOx) and glucose ____2____ (GDH).
In nature, ____1____ enzymes such as GOx act by oxidising their substrates, accepting electrons in the process and thereby changing to an inactivated ____3____ state.
A
- Oxidase
- Dehydrogenase
- Reduced
21
Q
State the advantages and disadvantages of glucose oxidase redox enzyme biosensors.
A
Advantages
- Inexpensive
Disadvantages
- Requires oxygen as a cosubstrate. Consequently, as oxygen is depleted in the sample, performance decreases.
22
Q
State the advantages and disadvantages of glucose dehydrogenase redox enzyme biosensors.
A
Advantages
- Oxygen independent
Disadvantages
- The cofactor (NAD+) is expensive and unstable
23
Q
State the chemical equation that happens in a glucose oxidase redox biosensor.
A
Glucose + O2 → gluconolactone + H2O2
24
Q
State the chemical equation that happens in a glucose dehydrogenase redox biosensor.
A
Glucose + NAD+ → gluconolactone + NADH
25
The earliest approaches to the construction of amperometric glucose biosensors were based on GOx immobilised close to an electrode. The depletion of oxygen was monitored, using a ______ oxygen electrode
Clark
26
What are the advantages of using a redox mediator in a biosensor? (3)
* They have a wide range of redox potentials
* The redox potentials are independent of pH
* Easy to manufacture
27
Name the analyte used in pregnancy testing.
Why is this used?
The hormone HCG.
HCG is present in pregnant women.
28
Redox enzymes can be divided into 2 classes depending on the mechanism of electron transfer.
What are they? + Examples?
* Intrinsic (e.g. Cytochrome c peroxidase)
* Extrinsic (e.g. Glucose oxidase)
29
Describe intrinsic redox enzymes. (3)
* Take part naturally in electron-transfer outside the confines of the enzyme.
* Electron transfer between prosthetic group and substrate in vicinity of active centre.
* No requirement for ET pathway from active site to protein surface.
30
Describe extrinsic redox enymes. (4)
* Electron transfer occurs within the confines of the enzyme.
* Difficult to achieve electron transfer between electrode surface and enzyme active site.
* Electron donating or accepting species required (co-substrate) which binds at site remote to active centre.
* Electron transport pathway presumed to exist between co-substrate binding site and active centre --- possibly involves enzyme surface.
31
What is the difference between intrinsic and extrinsic redox enzymes?
The positioning of the active site within the structure.
32
Free radicals (O2ˉ and NO) are continuously generated during cell \_\_\_\_1\_\_\_\_ and \_\_\_\_2\_\_\_\_.
1. Respiration
2. Metabolism
33
Define lipid peroxidation.
Lipid peroxidation is the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage.
34
_Lipid Peroxidation_
**Initiation**
* Reactive oxygen species (ROS), such as OH·, O2ˉ and NO, combine with a hydrogen atom to make \_\_\_\_1\_\_\_\_ and a fatty acid radical.
**Propagation**
* The fatty acid radical reacts with molecular oxygen to create a lipid peroxyl radical.
* This radical reacts with another free fatty acid, producing a different fatty acid radical and a lipid peroxide, or a \_\_\_\_2\_\_\_\_ peroxide if it reacted with itself.
* This cycle continues, as the new fatty acid radical reacts in the same way.
**Termination**
* When a radical reacts with a non-radical, it produces another radical, resulting in a "chain reaction mechanism".
* This radical reaction can only be stopped by the interaction of two radicals to produce a non-radical species.
* In nature there are specific molecules that accelerate termination by capturing free radicals and preventing them from damaging the cell \_\_\_\_3\_\_\_\_.
* Antioxidants include vitamins A, C and E. Other anti-oxidants are enzymes and include superoxide dismutase, catalase, and peroxidase.
**Final products of lipid peroxidation**
* The end products of lipid peroxidation are reactive \_\_\_\_4\_\_\_\_, such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE).
1. Water
2. Cyclic
3. Membrane
4. Aldehydes
35
Xanthine oxidase catalyses the conversion of xanthine to uric \_\_\_\_1\_\_\_\_ and superoxide (O2- free radical).
This is our method of generating superoxide at will.
We can therefore design a biosensor for free radical/oxidative stress ex vivo.
Transfer of \_\_\_\_2\_\_\_\_ is the same as cyto c peroxidase, just with superoxide instead.
1. Acid
2. Electrons
36
Define amperometry.
The detection of ions in a solution based on electric current or changes in electric current.
37
_Amperometric Glucose Measurement_
38
_Amperometric Glucose Measurement_
39
_Amperometric Glucose Measurement_
40
**Read**
## Footnote
In medical and biochemical research, when the domain of the sample is reduced to micrometer regimes, e.g. living cells or their subcompartments, the real-time measurement of chemical and physical parameters with high spatial resolution and negligible perturbation of the sample becomes extremely challenging.
The larger the sensor the more it can detect and therefore it can be less sensitive.
The smaller the sensor the less it can detect and therefore it must be more sensitive to retain functionality.
A traditional strength of chemical sensors (optical, electrochemical, etc.) is the minimization of chemical interference between sensor and sample, achieved with the use of inert, ‘biofriendly’ matrices or interfaces.
However, when it comes to penetrating individual live cells, even the introduction of a sub-micron sensor tip can cause biological damage and resultant biochemical consequences.
In contrast, individual molecular probes (free sensing dyes) are physically small enough but usually suffer from chemical interference between probe and cellular components.
41
What are PEBBLE sensors (Probes Encapsulated By Biologically Localized Embedding)?
Nano-scale spherical devices consisting of sensor molecules (fluorescent sensing dyes) entrapped in a chemically inert matrix.
42
PEBBLE sensors (Probes Encapsulated By Biologically Localized Embedding) are nano-scale spherical devices consisting of sensor molecules (\_\_\_\_1\_\_\_\_ sensing dyes) entrapped in a chemically inert matrix.
This protective coating eliminates interferences such as protein binding and/or membrane/organelle sequestration which alter dye response.
Conversely, the nanosensor matrix also provides \_\_\_\_2\_\_\_\_ to the cellular contents, enabling dyes that would usually be \_\_\_\_3\_\_\_\_ to cells to be used for intracellular sensing.
In addition, the inclusion of reference dyes allows quantitative, ratiometric fluorescence techniques to be used.
PEBBLEs have been used to measure \_\_\_\_4\_\_\_\_ such as calcium, potassium, nitric oxide, oxygen, chloride, sodium and glucose.
1. Fluorescent
2. Protection
3. Toxic
4. Analytes
43
Define ratiometric.
Describing any system in which an output is directly proportional to an input.
44
One of the advantages of the nanosensors are that they are \_\_\_\_\_\_.
Ratiometric
45
_Fibre-Optic Precursor Technology_
Pulled (tapered) fibre optic probes as intracellular sensors have been used. The tips of these fibres were either coated with a layer of plasticized PVC (glue) containing sensor materials, or they had a small amount of sensor material on the end which was photo-polymerized. The sensor materials stuck down by the PVC polymer are effectively fluorophores. This fluorophore responds to pH.
The probe is pushed through the cell membrane into the intracellular space. Any changes in pH in this immediate area will be recognized by the probe causing the fluorophore to fluoresce. This light then travels down the fibre and can be measured. The level of fluorescence is dependent on the pH.
What are the major problems of this technology? (3)
* Made a big hole in the membrane (to get the probe into the cell). This causes damage and can lead to apoptosis.
* Can only measure pH changes in the small vicinity of the fibre tip. This is unlikely to give an accurate representation of the entire cell.
* Entire fibre is very big in relation to the cell meaning that a maximum of only 2 or 3 fibres could be used on a single cell. Therefore you cannot make up for the second problem. Multiple fibres in a single cell would likely kill the cell regardless.
46
Name the 2 major problems with free sensing dyes.
What nanoscale biosensor technology overcomes this?
* The fluorescence intensity will change from cell to cell due to the different concentrations of dye in each cell.
* Interference by things like non-specific protein binding (which happens a lot in a cellular environment).
PEBBLEs
47
What delivery method is used for inserting PEBBLEs into cell culture?
Give an advantage of this.
Give a disadvantage of this
Gene gun.
## Footnote
**Advantage** - This method forces the nanosensors through the cell membrane into the cytoplasm and are even forced into the nucleus (which makes the Gene Gun especially useful).
**Disadvantage** - Punctures the cells leaving holes in them. Like the fibre-optic method can cause apoptosis and cell death. Some of the fired nanosensors pass right through the cell.
48
What is the advantage of using a gene gun as a PEBBLE delivery method?
Good penetration. This method forces the nanosensors through the cell membrane into the cytoplasm and some are even forced into the nucleus.
49
What is the disadvantage of using a gene gun as a PEBBLE delivery method?
Often too destructive. It punctures the cells leaving holes in them. Like the fibre-optic method can cause apoptosis and cell death. Some of the fired nanosensors pass right through the cell.
50
Explain the technique of using phagocytic cells as a delivery method for nanosensors.
How do we achieve this?
What is the disadvantage?
We can use the cells innate properties (phagocytic macrophage cells). These cells internalize anything that is deemed damaging to the host. We can trick them into internalizing our nanosensors.
We achieve this by growing the macrophages in a medium that contains our nanosensors. Once the macrophages come into contact with the nanosensors they internalize them.
The disadvantage is that this technique only works with phagocytic cells and most cells are not.
51
Explain the technique of using the liposomal transfection process as a delivery method for nanosensors.
Uses a transfection reagent which is basically strands of lipid. If the nanosensors are incubated with this lipid, the lipid forms vesicles around the nanosensors trapping them inside. The liposomes then fuse with the cell membrane and release their contents (nanosensors) into the intracellular space.
52
Describe the nanosensor fabrication process.
1. Water in oil micro-emulsions are used for the synthesis in an argon rich environment.
2. Any solvent is then distilled off (has the nanosensors dissolved within).
3. Solvent is then dried in vacuum to produce the nanosensor powder with can be stored.
53
Besides incorporation of many different sensing constituents, PEBBLEs have the advantage that it is possible to attach other molecules to the outside of the \_\_\_\_1\_\_\_\_, allowing specific attachment at cellular membrane sites.
The method involves \_\_\_\_2\_\_\_\_ of the PEBBLEs using a mixture of monomers, some having free amine groups.
Some of these groups will be exposed on the outside of the PEBBLE, and simple attachment can be made to other molecules (like biotin) through carboxyl or succinimydal \_\_\_\_3\_\_\_\_ groups.
1. Matrix
2. Polymerization
3. Ester
54
_Background of ME/Chronic Fatigue Syndrome (CFS)_
ME/CFS is characterised by profound \_\_\_\_1\_\_\_\_ which frequently has a significant impact on quality of life.
When ME/CFS patients undertake a standard level of peripheral muscle exercise they show marked abnormality of bio-energetic function (assessed using fMRI).
Over-utilisation of anaerobic metabolism pathways will limit capacity to exercise through ______ 2 ______ accumulation and lead to the perception of \_\_\_\_1\_\_\_\_.
1. Fatigue
2. Lactic acid
55
_Optical Nanosensors_
* Designed to address the limitations of standard fluorescent probes
* Produced by microemulsion polymerisation techniques – porous polyacrylamide matrix
* Spherical in shape: 20 - 200nm diameter
* Introduced into cells via lipid transfection
What are the advantages of using optical nanosensors? (2)
* Matrix protects fluorophore from NSB (e.g. protein)
* Matrix protects cell from fluorophore toxicity
56
\_\_\_\_\_\_ 1 \_\_\_\_\_\_: The liver is severely scarred but there are enough healthy cells in your liver to perform all of its functions adequately.
\_\_\_\_\_\_ 2 \_\_\_\_\_\_: The liver is not capable of performing all of its normal functions resulting in a number of complications including, fluid retention and mental confusion (encephalopathy)
1. Compensated cirrhosis
2. Decompensated Cirrhosis
57
_Side effects of decompensated cirrhosis_
\_\_\_\_1\_\_\_\_– Accumulation of fluid in the abdomen around the liver. Can be fatal due to fluid stopping the diaphragm from working thereby suffocating the individual due to loss of lung function.
\_\_\_\_\_\_ 2 \_\_\_\_\_\_– Form of dementia. Caused by the failing liver being no longer able to metabolise ammonia. Ammonia levels build up in the blood and reach the brain causing the illness.
\_\_\_\_3\_\_\_\_– Blood flow through the liver is impeded by fibrosis, tumours etc. This leads to a build up of pressure caused by the blood trying to enter the liver but failing. This increases the blood pressure in the blood vessels that supply the liver causing the vessels to bulge out to form varices.
1. Ascites
2. Hepatic encephalopathy
3. Varices
58
\_\_\_\_\_\_ ______ \_\_\_\_\_\_- The failing liver with not be able to deal with biosalts in the way a healthy liver could. The biosalts then enter the blood and are deposited under the skin. This causes a relentless itch that cannot be got rid of.
Chronic cholestatic itch
59
There are too few available cells in the liver to be used to make an artificial liver. Therefore scientists use cells from the \_\_\_\_\_\_.
Pancreas
60
From a clinical perspective there are 6 key parameters that must be measured to monitor liver function:
Name them.
* Bilirubin
* Albumin
* Creatinine
* Sodium
* Potassium
* Blood clotting time (increase = bad)
61
Define microfluidics.
Design of systems in which low volumes of fluids are processed to achieve multiplexing, automation, and high-throughput screening.
62
State the advantages of microfluidics. (5)
* Low fluid volumes consumption
* Faster analysis and response times due to short diffusion distances
* System is compact
* Parallelization allows high-throughput analysis
* Lower fabrication costs
63
State the disadvantages of microfluidics. (2)
* Detection principles may not always scale down
* The absolute geometric accuracies and precision in microfabrication are high
64
_d-Liver_
Physiological parameters measured by sensors on chest –\_\_\_\_1\_\_\_\_ measurement
Biochemical parameters measured by microfluidic sensor –\_\_\_\_2\_\_\_\_ measurement
1. Passive
2. Active
65
Name the 4 physiological parameters measured by the d-Liver.
* Heart rate
* Skin body temperature
* Activity/Posture
* Blood pressure
66
Define Pulse Transit Time (PTT).
The time taken from the opening of the heart valve until the blood pressure wave reaches the periphery. PTT depends on blood pressure; higher pressure correlates to shorter PTT.
67
What sensor is used to detect the heartbeat start impulse?
Electro CardioGraphy (ECG)
68
What sensor is used to detect opening of the aortic valves?
Impedance CardioGraphy (ICG)
69
What sensor is used to detect peripheral pressure waves?
PhotoPlethysmoGraphy (PPG)
70
Describe the process of measuring blood clotting analysis. (5)
1. The sensor is composed of a complementary metal-oxide semiconductor (CMOS) sensor on which the fluidic component is put
2. The sample fills the channel by capillarity.
3. A laser source illuminates the blood sample and red blood cells diffuse light.
4. A moving diffraction picture is formed on the CMOS sensor called speckle diffraction.
5. When the blood clots, the movement stops. Clotting is then detected.
71
Define potentiometry.
The measurement of electrical potential as a technique in chemical analysis.
72
73
74
The bioreactor is a network of tubes.
Cells enter via inoculation tube. The cells spread out and populate the entire reactor. The cells are kept healthy by the constant perfusion of air and oxygen and the removal of old medium and CO2 from the respective inlet/outlet tubes.
75
Define Micro Electro Mechanical Systems (MEMS).
A functional unit that contains electrical and mechanical components for sensing or actuation. The characteristic size of at least one x, y or z dimension must be at the micron scale.
76
What does an actuator do?
An actuator takes one type of energy and transfers it to another type. E.g. an actuator can turn electrical energy into mechanical energy (and therefore motion).
77
What is a cantilever?
A rigid structural element, such as a beam or a plate, anchored at only one end to a (usually vertical) support from which it is protruding.
78
Force effects (i.e. ______ that hold proteins together) only work on the micro/nano scale.
Bonds
79
What is a piezoelectric material?
Certain ceramic and crystalline materials that display a linear electromechanical response to mechanical stress or vibration or an electric field.
80
If you input a voltage to a piezoelectric material, as the voltage changes it changes the \_\_\_\_1\_\_\_\_ in the material. As this changes the material \_\_\_\_2\_\_\_\_. This is a mechanical effect.
Piezoelectric materials can be used in both sensors and actuators.
1. Charge
2. Deforms/changes shape
81
\_\_\_\_\_\_ = area of electrode / distance between electrodes
Capacitance
82
# Define the piezoresistive effect.
How is it different to the piezoelectric effect?
A change in the electrical resistivity of a semiconductor or metal when mechanical strain is applied.
In contrast to the piezoelectric effect, the piezoresistive effect causes a change only in electrical resistance, not in electric potential.
83
The main problem of electrostatic effect is that it decreases with the ______ of the distance between the two charged bodies.
Square
84
Define actuation.
The electrostatic force (attraction) between moving and fixed plates as a voltage is applied between them.
85
Define electrostatic sensing.
The capacitance between moving and fixed plates change as distance and position is changed.
86
Why use microneedles (microcantilevers) for transdermal delivery? (4)
* Shallow penetration reduces chance of infection.
* Drugs with larger molecular sizes.
* Delivery where drugs are most effective (lower dosage).
* Virtually painless.
87
Why is a clean room necessary for microfabrication?
To prevent any skin, hair, dust etc. contaminating the microscopic MEMS device.
88
Define microfabrication.
Is the process of fabricating miniature structures of micrometre scales and smaller.
89
\_\_\_\_\_\_ ______ are used as the starting material in nearly all microelectronics as it can be doped to a be semiconductor.
## Footnote
*(In electronics - doped = add an impurity to (a semiconductor) to produce a desired electrical characteristic.)*
Silicon wafers
90
Describe the Czochralski process. (5)
1. Start with single seed of silicon crystal in a certain orientation on a rod
2. Rod is dropped into container filled with molten silicon
3. Rod is rotated, spinning the seed
4. Slowly lifting up, the molten silicon attaches to the seed and builds up the ingot
5. Ingot is then cut up into slices to produce the starting material
91
Silicon has 4 electrons in its outer shell and therefore it can make 4 bonds with other things (not because there are 4 electrons, but because there are 4 electrons needed to fill the outer shell of \_\_\_\_1\_\_\_\_). To produce the crystal structure of the wafer the silicon forms tetrahedral bonds with other silicon. As all the bonds are now used the silicon wafer is an \_\_\_\_2\_\_\_\_ (cannot conduct electricity due to no free electron). To make current flow through the wafer we can attach positive (e.g. boron) and negative (e.g. phosphorous) \_\_\_\_3\_\_\_\_. Boron has \_\_\_\_4\_\_\_\_ electrons in its outer shell and this interferes with the silicon by causing the silicon bound to the boron to have a free electron (only \_\_\_\_4\_\_\_\_ needed to fully bind boron). This free electron is then able to move through the silicon lattice and conduct electricity. Phosphorous has \_\_\_\_5\_\_\_\_ electrons in its outer shell. When the phosphorous binds to the silicon it has one electron free and this electron is able to travel through the lattice and conduct electricity. Difference between positive and negative doping is just which molecule donates the free electron.
1. 8
2. Insulator
3. Dopings
4. 3
5. 5
92
Define doping (electronics).
In semiconductor production, doping intentionally introduces impurities into an extremely pure intrinsic semiconductor for the purpose of modulating its electrical properties.
93
What is the first step of the microfabrication process?
The removal of contaminating particles from materials.
94
_Growth at silicon/oxide interface_
What is the growth rate determined by? (2)
* Rate of converting silicon to oxide at interface (increases with temperature).
* Diffusion of oxygen through oxide layer (increases with pressure).
95
How are metals and piezoelectric materials deposited on the silicon wafer?
Through Physical Vapor Deposition (PVD).
96
Define Chemical Vapor Deposition (CVD).
Deposition of a solid on a heated surface from a chemical reaction in the vapour phase.
97
Define photolithography.
The process of transferring geometric shapes on a mask to the surface of a silicon wafer.
98
Define a photoresist.
A light-sensitive material used in several industrial processes, such as photolithography and photoengraving, to form a patterned coating on a surface.
99
Define electron-beam lithography.
The practice of scanning a focused beam of electrons to draw custom shapes on a surface covered with an electron-sensitive film called a resist.
100
# Define an isotropic material.
Define an anisotropic material.
When the properties of a material are the same in all directions, the material is said to be isotropic.
When the properties of a material vary with different crystallographic orientations, the material is said to be anisotropic.
101
Name and describe the 2 types of etching.
**Wet etching** (chemical)
* Generally isotropic.
* Can be anisotropic for single crystal substrates where etch rate can vary on direction in crystal.
**Dry etching**
* Generally anisotropic due to direction of gas ions striking surface perpendicularly.
102
Describe, step by step, the microfabrication of a microcantilever. (7)
1. Grow oxide (thermal oxidation)
2. Photolithography patterns oxide (sacrificial layer)
3. Remove visible oxide etch
4. CVD polysilicon device layer
5. Photolithography patterns polysilicon structural layer
6. Etch polysilicon
7. HF etch of sacrificial layer.
103
Define a BioMEMS.
A MEMS functionalised with a recognition bio-molecule that can pull down a specific target molecule and lead to a physical mechanical change that can be observed.
104
Is a higher or lower limit of detection (LOD) better?
Why?
Lower.
Because it means it can detect smaller variations.
105
Define a cantilever.
A beam anchored at only one end.
106
Microcantilevers can be designed to be rigid or flexible depending on their application.
In micro needles the probes must be stiff enough to penetrate the \_\_\_\_1\_\_\_\_ without bending.
Cantilevers in chemical or biochemical sensor are designed to be \_\_\_\_2\_\_\_\_. Their method of signal transduction is mechanical deflection or dynamic mechanical motion.
1. Skin
2. Flexible
107
Kspring = EWT3 / 4L3
* E= material elasticity (measure of material stiffness)
* W= cantilever width
* T= cantilever thickness
* L= cantilever length
Kspring = spring constant. The ______ the spring constant, the stiffer the material is.
The ______ the Young’s modulus is, the stiffer the material is. Equation proves that long, thin and low width cantilevers have low stiffness (high flexibility). Equation proves that short, thick and wide cantilevers have high stiffness (low flexibility).
Higher
108
Why use microcantilevers as BioMEMS?
Micro-cantilevers capitalise on attributes that scale advantageously as physical size is reduced. They are scaled to a physical size at which you could expect to see a mechanical effect due to analyte binding.
109
Define resonance (physics).
The tendency of a mechanical system to oscillate with greater amplitude at certain frequencies.
110
Add mass to cantilever = ______ the resonant frequency.
Decrease
111
What separates the environment from the BioMEMS device?
The Bio-interface.
112
Give examples of recognition molecules used in the bio-interface. (5)
Which is the most commonly used? Why?
* Antibodies
* Receptors
* DNA and RNA aptamers
* Peptide aptamers
* DNA Waston-Crick Base pairing
Antibodies are the primarily used molecule in the bio-interface because they have strict specificity and we can design them easily to our needs.
113
Define physisorption
Physical adsorption; the weakest form of adsorption. Lacks a true chemical bond.
114
Define chemisorption.
Adsorption which involves a chemical reaction between the surface and the adsorbate. New chemical bonds are generated at the adsorbent surface.
115
_Effects of down-scaling for MEMS devices_
**Force effects**
* ?
**High surface to volume ratio**
* ?
* ?
**Manufacturing inaccuracy**
* ?
**Reduced time constants**
* ?
**Lower power consumption**
* ?
State the down-scaling effect of each and whether the effect is positive or negative.
**Force effects**
* E.g. (length)2 dependence for electrostatic forces ✔
**High surface to volume ratio**
* Good thermal dissipation ✔
* High frictional forces ✖
**Manufacturing inaccuracy**
* Relatively large tolerances required ✖
**Reduced time constants**
* Faster response time of sensor ✔
**Lower power consumption**
* Greater energy and cost efficiency ✔
116
_The main danger in miniaturisation/MEMS_
As devices become smaller on the nano and micron scale then the ______ \_\_\_\_\_\_ ______ \_\_\_\_\_\_ \_\_\_\_\_\_becomes larger and surface effects become dominant.
The phenomenon of protein molecules aggregating, or sticking at a surface is similar.
Surface area to volume ratio
117
The economist, ______ \_\_\_\_\_\_, advocates that a new technology has historically taken 28 years to gain wide acceptance, once accepted rapid growth ***may*** occur for an additional 56 years.
Norman Poire
118
_MEMS Accelerometers_
When the object on which the accelerometer is mounted moves or vibrates, the proof mass detects and “\_\_\_\_\_\_” the movement. The spring constant of material allows the movement of the proof mass. The distance moved (Z) is a factor of the acceleration (A), proof mass size (M), and the spring constant (K) of the material.
Z= ?
Copies
Z = (MxA) / K
119
Micro-needles have the ability to deliver \_\_\_1\_\_\_ and sample fluids painlessly because they are short enough to avoid ______ 2 ______ located in the \_\_\_3\_\_\_.
1. Drugs
2. Nerve endings
3. Dermis
120
Why use microneedles for transdermal delivery? (4)
* Shallow penetration reduces chance of infection.
* Drugs with larger molecular sizes.
* Delivery where drugs are most effective (lower dosage).
* Virtually painless.
121
Regarding microfabrication, name the 3 techniques used to deposit layers onto the basic silicon wafer.
* Thermal oxidation
* Chemical vapour deposition
* Physical vapour deposition
