Lecture 6A

 Plasma – Fourth state of matter

 When gas deionizes, we get plasma and when plasma ionization occurs, we get gas
 So, plasma contains freely moving protons and electrons
 Examples of complex plasma in real world are:
1. Comet rails
2. Planet rings
3. Noctilucent clouds
Which all are present in the upper atmosphere
 Some of the major industrial applications of plasma are
1. Plasma etching of silicon wafer in microelectronic industries
2. Used in fossil fuel MHD power generator
3. Use in solid fuel rocket exhausts
 One of the typical creations of artificial plasma is in fusion reactors. The heat the
gas to the very hot temperature. This leads to formation of plasma and when further
heated the fast-moving ions collide and release enormous amount of energy. This
energy can be captured and converted into electrical energy. But this process is very
dangerous as it follows the same principle based on which the sun glows.
 One such typical fusion reactor is a C – mod “tokamak” style reactor. It will be in the
shape of a doughnut with powerful magnets. These magnets help to confine the
plasma and fuse them. If these magnets are not present then the chamber walls will
turn into liquid metal
 There are two types of plasma
1. Thermal plasma
 All the energy are equally delivered to the gas ions thus a thermal
equilibrium or near equilibrium can be formed between electrons, ions and
neutrals.
 High temperature type with temperature range upto 10 to 10000s of kelvin.
 Difficult to control
 Energy costs and maintenance cost are high
2. Non-Thermal Plasma
 Once gas ionized the most of the energy are primarily delivered to the
energetic electrons rather than heating up the gas
 Low temperature process sometimes available in room temperature also
 Easy to control
 Maintenance and energy costs are much lower than thermal plasma
Other ways of Categorizing plasma are based on density and pressure like high or low density
or pressure plasma
Generations of plasma
1. Gas Discharge
There are two mechanisms to explain gas discharge
i. Townsend Mechanisms
 Process of electron multiplication in a gas filled space at low pressure and
when an electric field is applied across the gas.
 Electron Generation: In the absence of an electric field, a few
electrons are naturally present in the gas due to thermal excitation.
These are called seed electrons.
 Electron Acceleration: When an electric field is applied, the seed
electrons are accelerated in the direction of the field. If the electric
field is strong enough, these electrons can gain enough energy to
collide with gas molecules.
 Impact Ionization: When a seed electron collides with a gas
molecule, it can transfer enough energy to ionize the gas molecule.
Ionization results in the creation of additional electrons and positive
ions.
 Electron Avalanche: The newly created electrons are then
accelerated by the electric field and can, in turn, collide with other
gas molecules, causing further ionization. This process continues,
resulting in an exponential increase in the number of electrons in the
gas.
 Sustained Discharge: If the electric field is maintained, the electron
avalanche continues to grow, and a sustained electrical discharge
occurs, with a large number of electrons and ions present in the gas.
 used in the design and operation of gas-filled tubes, such as fluorescent
lamps, neon signs, and gas lasers
ii. Streamer Mechanism
Phenomenon that occurs in gas-filled spaces under the influence of high
electric fields. Unlike the Townsend discharge mechanism, which describes a
relatively uniform, sustained discharge, the streamer mechanism pertains to
the development of localized, branched discharges known as streamers.
 The streamer mechanism typically requires the application of a high
electric field in the gas.
 Electron Acceleration
 Ionization and Electron Multiplication
 Formation of Streamers
 Rapid Propagation: Streamers propagate through the gas with high
velocities. They branch out and continue to grow and evolve as they
move through the gas.
 Completion of Discharge: Eventually, the streamers may reach the
opposing electrode or dissipate in some manner.
 Key feature in phenomena like corona discharges, which occur
around high-voltage conductors and are responsible for the hissing or
crackling sounds you might hear near power lines during stormy
weather.
Different applications via gas discharge methods:
i. Corona – applying electric filed on high conductive materials ionizes and
produces plasma from the surrounding gas
 ii. Gliding arc – Remember ignition, propagation and cut off of plasma
iii. Plasma jet
iv. Transient spark
2. Dielectric barrier discharge
 A dielectric barrier discharge (DBD) is a type of electrical discharge that
occurs between two electrodes separated by a dielectric material, such as
glass, ceramic, or plastic.
 This dielectric material provides a control over the creation of plasma in the
gap
 They are often associated with non-thermal plasma because of their
relatively lower temperature
 To initiate the discharge stronger electric field is required but later that
stronger filed is not required
 Typically, in laboratory scale happens at low pressure 3.1- 3 bar, with gap size
between the electrodes 0.1 – 5 mm and very low voltage applied which can be
controlled to control the plasma creation
 Micro discharge filaments can be used for this with a near cylindrical radius of
100 microns and only wit a duration varying from 10 to 50 ns.
 Packed bed DBD the packings help in uniform distribution of gasses and thus
a larger surface area for the plasma to interact with surrounding gasses
Microplasma
The breakdown voltage for deionizing the gas depends on
1. Gas composition
2. Pressure
3. Distance between electrodes
From the Paschens curve it is understood that for a minimum pressure the break up voltage
required is minimum but afte that for evey increase in pressure the volatge required increases
which is waste of energy and alos below that pressure we rqeuire high volatage to start the
break up of ions. SO even for a atmospheric plasma with centimeters of distance requires a
large voltage. This hight breakdown vcolatge leads ot instable operation, saftey issues and
more.
Advantages of micro plasma:
 Localized hating
 Precise control
 Low operating temperature
 Compact geometry
 Increased surface to volume ratio
 Decreases electrode spacing
 Reduce voltage
Disadvantages of Micro plasma
  Low power density (Power density = (Power/Volume) – ie power distributed over a
certain area or volume)
 Need to control gas flow to achieve uniform gas distribution which is difficult
 Complex system design
 Challenging to understand the system and its parameters to produce the desired
outcomes
Typical application of Gas liquid microfluidic plasma reactors is:
 Water treatment / Oxidation process
 Synthesis of nano materials
 Cleaning and modification of microfluidic reactors

General Introduction to Non-Thermal Plasma Chemistry

Three types:
i. Thermal Chemistry – Heat source
ii. Non-Thermal Chemistry – Reaction initiated by energetic electrons
iii. Photochemistry – Light source
Difference between thermal and non-thermal plasma chemistry (TPC and NTPC)
1. Temperature
 TPC – Electrons and gases have high temperature due to thermal equilibrium
 NTPC – Since no thermal equilibrium exists the electron temperature are
much higher compared to the gas temperature or it can be lower also
2. Energy distribution:
 TPC - Most electrons have relatively same and high energy levels
 NTPC – Range of electron energy level exists
3. TPC are non-controllable and NTPC are controllable
In NTPC two main process occur:
1. Primary process
 Occurs as various high energy electrons collide with gas molecules in various
ways to produce highly reactive species. The primary process include:
i. Ionization
ii. Dissociative ionization
iii. Electron attachment
iv. Dissociative electron attachment
v. Excitation
vi. Dissociation
2. Secondary process:
 Includes reaction between the reactive species produced in the primary
process. These reactions include:
i. Gas phase reaction to form new compounds
 ii. Surface reactions – interact with surfaces leading to surface
modification
iii. Radial-molecule reaction
iv. Ion-molecule reaction
Example: Production of No and NO2 form using air (Slide – 21)
Time scale of process in atmospheric non-thermal plasma includes over 12 orders of
magnitude.
From the DBD plasma graph in slide 24 for a fixed voltage, power and frequency:
 As flow rate increases the conversion decreases and for a fixed flow rate lower
size channel has good conversion
 Also, as residence time increases the1 conversion in the plasma channel
increases and also for a fixed residence time lower size channel has more
conversion.
Electron Energy Distribution function (EEDF)
The rate of such process depends upon the number of electrons present which has the
sufficient energy to the job. That is, it depends on electron density (Number of electrons per
unit volume)
EEDF tell about the number of electrons that are present at each energy levels which often
depends on the electric field or voltage applied and gas composition.
Reduced Electric field (REF)
Ratio of electric filed (E in V/m) to the number density of gas molecules (N in m^-3). It
describes the mean energy acquired by each electron as they move through the gas. This REF
relates it to the mean free path which is the average distance an electron travels between two
collisions. So, if there is high REF then the mean free path will be longer for electrons.
Unit of REF: V m^2 or Td. {1 Td = 10^ (-21) V m^2}
From slide 28 and 29:
1. Specific Energy Input
2. Absolute conversion of reactant i
3. Effective conversion of reactant i
4. Total Conversion
5. Energy efficiency
6. Energy consumption
Plasma catalysis
In plasma catalysis, a plasma is generated in the vicinity of a catalyst, which can be a solid,
liquid, or gaseous material. The catalyst facilitates the formation of reactive species, such as
ions, electrons, radicals, and excited molecules, within the plasma. These species can then
participate in chemical reactions to drive various processes.
Can be used for various purposes like:
 i. Air cleaning
ii. Flue gas cleaning
iii. Water treatment
iv. NH3 synthesis
Plasma – Catalyst interactions
i. Plasma to Catalysts (advantages)
 Hot spot formation – significantly increase the catalytic activity
 Reduce coke formation and chances of catalytic poisoning
 Lower activation barrier
 Changes the morphology and physiochemical characteristics
ii. Catalyst to plasma
 Electric field enhancement
 Formation of micro discharges in pores
 Change in discharger type
 Changes in plasma density

In summary:
Plasma process have following characteristics
i. Mild reaction condition (Low temp and atmospheric pressure)
ii. Instant control over reaction (On-off electric field)
iii. Available in small scale and portable
iv. Easy to be used with renewable energy when the electric source comes from the
renewable source and most cases air is used as the gas for plasma
v. Green environment profile
vi. Low investment and operation cost
Aspects Microplasma Conventional plasma
Operating pressure Atm pressure Needs low pressure (See
Paschens principle)
Gas temp Low temp or room temp High temp above 1000 C
Particle size and distribution Fine size and narrow size Larger size and wider size
distribution distribution
Setup and investment Portable, small and low cost Non portable, large size and
more costs

Diagnostics of Plasma
Desired properties or important parameters required to study plasma are:
i. Voltage
ii. Current frequency
iii. Gas composition
iv. Flow rate
v. Pressure
 vi. Electric field
vii. Electron density
viii. Temperature profile
ix. Ions
x. Radicals
xi. Neutrals
Now to analyze the plasma there are two ways:
i. Electrical diagnostics
 We measure electric characters like voltage and current
 Circuit is analyzed
 Energy calculations done
ii. Optical diagnostics
 Optical emission spectroscopy (OES)
Involves analysis of emitted light from plasma. Provides info about energy
levels, composition and temperature of plasma. Atomic and molecular
transitions can also be identified allowing for determination of species
conc.
 Optical Absorption Spectroscopy (OAS)
Wavelength of the absorbed light gives about what species is present in the
plasma.
 Laser induced fluorescence (LIF)
Laser used to excite specific atomic or molecular species within the
plasma. The emitted fluorescence light is then analyzed to measure species
concentrations and temperature with high precision.
Note: Non-intrusive probes (Type of sensor which do not interfere with the system because
they don’t come in direct physical contact with the system) are good for these kind of studies
as they do not interfere with plasma. But for more accurate measurement intrusive probes
are required and that comes at the cost of altering system properties since a foreign element
comes in physical contact with the system.
Electrical Diagnostics
Most widely used electrical diagnostics to analyze plasma is Langmuir probes (Intrusive
probes). They consist of metal electrodes that are inserted into the plasma. By measuring the
current-voltage characteristics pf the probe one can determine parameters like electron
density, electron temperature and plasma potential.
Note: A spark discharge, often simply referred to as a spark, is a sudden and visible
electrical discharge that occurs when there is a breakdown in the dielectric strength of a
medium (such as air) due to the application of a high voltage.
Optical Diagnostics
i. Electronic Transitions
 Transition between two different energy levels. So they give
 Mostly observed in UV/Visible spectral range
  So, absorption of UV/Visible light can be used to study electronic
transitions
 Analysis of electronic transition gives details about the different energy
levels present in plasma
ii. Vibrational transitions
 Transition happening within a single energy level.
 This gives information about modes of molecules and their energy levels
 Mostly observed in Infrared spectral range.
iii. Rotational Transitions
 Further transition inside each vibrational band
 Mostly observed by Microwave spectral range
 Gives information about precise molecular identification and structural
analysis.

Lecture 6B
Electron temperature and Gas temperature in plasma
Electron temperature
 Average kinetic energy of electrons within the plasma
 More the electron temperature more excitation of atoms or molecules can
be seen
 The electron temperature strongly influences the electrical conductivity of
the plasma. Higher electron temperatures lead to increased electron
mobility, resulting in higher electrical conductivity.
 It can influence or affect the various process happening inside the plasma
like ionization, dissociation, excitation etc.
 The kinetic energy of the free electrons (i.e., their temperature) is directly
related to the electronic excitation temperature of the bound electron in
an atoms or molecules in the plasma.
Note:
i. Electronic excitation temperature - average energy of these bound electrons as
they transition to higher energy states
ii. Bound electrons - electrons that are closely associated with and bound to the
nuclei of atoms or ions within the plasma. They are tightly bound to these energy
levels and do not move freely throughout the plasma.
iii. Unbounded electrons - Unbound electrons, also known as free electrons, are
electrons that have gained sufficient kinetic energy to overcome the attractive
forces of the atomic nuclei. They are not confined to specific energy levels and are
free to move throughout the plasma.
There is an electrostatic Langmuir probe way to find this electronic temperature. Here it
can be experimentally obtained from the second derivative (d2I/dV2) of the probes current-
voltage characteristics. But this methos is limited due to:
i. Difficulty in analyzing the presence of negative ions
ii. Gets affected when there is fast change in plasma parameters
iii. Difficult to use for small volume of plasma

iGas temperature
The gas temperature is defined as the average kinetic energy of the gas particles, which
includes electrons, ions, and neutrals.

Optical emission spectroscopy for measurement of gas temperature

When it comes to measure the temperature at 1 millisecond resolution it is not possible with
any temp measuring device. So, there we go for spectroscopy.
Laser induced Rayleigh scattering - Peaks obtain when laser hit the electrons helps to
calculate the temp. In this methos you take two gas one is air and other is plasma. Same
Rayleigh scattering is done for plasma and air. The air provides the reference intensity and
referent temperature. And with the intensity of the scattered light from plasma we will be able
to find the gas temperature. (See notes and slide 6)
In OES the optical radiation emitted from plasma are guided into a spectrometric system and
the detection with opto-electric receivers happen so here the plasma is not disturbed during
the measurement (non-intrusive probes)
If the plasma under OES is in the state of thermodynamic equilibrium, then the observe
line of intensities gives direct information about the number density of excited state in each
energy level and thus its slope of this plot (Boltzmann plot - Plot the natural logarithm of the
relative intensities (ln(I)) against the energy of the energy levels (E) associated with the
spectral lines) gives the temperature
Boltzman law:
k=A∗e ( −Ea/(k∗T))
plot: ln(I)=ln(A)− (E/( k∗T))
Slope = - 1/(T*k)
If the plasma is not in thermodynamic equilibrium, then the excitation kinetics can be studies
only via a model. The excitation densities should be mathematically formulated with the
plasma parameters like electron temperature and density and the relationship between the
excited population and the plasma parameters is described in a kinetic model which is
referred to as the collisional radiative model (CR model)
Limitations of this model: In this model all the ions are assumed to be singly charged and
can be only applied to study the discharge plasma of monoatomic gas species.
To find the electron density at a certain energy level P, firs with the help of this model we will
be able to find the population density of level p (Np) and then with this we find electron
density (Ne) (See slide 10) and then with the help of this Np we can also find Te (Electron
temperature) (See slide 11)
So, in some case the level pairs are strongly determined on any one of the plasma parameters,
Te or Ne. So, the to find them both we need two absorption curves whose intersection will
give the values.

Notes:
 More energy is required for Electron excitation
 Every vibrational transition is accompanied by several rotational transitions
 More difficult the rotation more energy need to be put into the plasma
 Rotation is waste of energy. We will be more interested in activating vibration
molecules
 For more vibration excitation we need to know about the Vibration temperature
 Nitrogen is added into the plasma system intentionally to measure the temp
 Why not CO2 used? CO2 has so many degrees of vibrations and degree of rotations
which makes it more complicated to measure the temp
 Rotational temp increases with energy as well as vibrational temp (more energy goes
to vibration only)
 But we need to limit the excitation of rotational temp as energy increases.
 Form the below graph it is understood that as the electron energy drops that energy
emitted is consumed by the vibrational and rotational temp and thus reaches a stage of
thermal equilibrium. The time for this thermal equilibrium is 1ms

Fourier transformed Infrared spectroscopy

  Composition Analysis: FTIR can be used to analyze the composition of a plasma. It
can identify the chemical species present in the plasma based on their characteristic
absorption and emission lines in the infrared spectrum.
 Temperature Measurement: FTIR can be used to measure the temperature of a plasma
by analyzing the emission or absorption lines of certain species. The temperature is
related to the shape and width of spectral lines, which can be obtained through
FTIR analysis.
 It is used to monitor the progress of reaction and identify the various intermediate
species that are formed during the course of the reaction.
 Adv:
i. Majority of molecules in a Non-Thermal Plasma (NTP) absorb mid-infrared
light making it highly useful tool.
ii. Highly sensitive and could be quantitative
iii. Inexpensive compared to other methods
 Disadv:
i. Cannot detect atoms or monoatomic ion since they do not contain chemical bonds
ii. Water vapor containing mixture are very hard to analyse as water vapor are strong
IR absorber
iii. Cannot detect non polar molecules like O2 or N2
Notes: (About FTIR)
 Is not fast (minimum time required for measurement by this method is 100 ms but the
typical residence time is 1ms)
 Mostly used for concentration measurement
Notes:
Diffuse Reflectance Infrared Spectroscopy (DRIFTS) and Fourier-Transform Infrared
Spectroscopy (FTIR) are both techniques used for analyzing materials, including in the
context of plasma diagnostics.
FTIR in Plasma: FTIR in plasma diagnostics typically involves studying the composition
and temperature of plasmas by analyzing the spectral lines of plasma emissions. FTIR
can provide information about the presence of different species in the plasma and their
temperature, which is valuable for understanding plasma properties and processes.
DRIFTS in Plasma: DRIFTS is less commonly used in plasma diagnostics, as it is
primarily designed for solid materials. However, it may find applications in
characterizing solid components or materials associated with plasma processes, such as
catalysts used in plasma-assisted chemical reactions.
Tunable Diode Laser absorption Spectroscopy (TDLAS)
 TDLAS is focused on a single absorption line in the absorption spectrum of a
particular species of interest. (High selectivity)
 The heart of TDLAS is the tunable diode laser. These lasers emit monochromatic
light in the near-infrared or mid-infrared range (Near-IR laser are much less
expensive compared to mid-IR lasers). The wavelength of the emitted light can be
precisely tuned over a narrow range by adjusting the laser's current or temperature.
  From this wavelength the intensity of the transmitted radiation is measured which can
be related to the concentration of species by beer-lamberts law.
 Beer-lamberts law
Describes the relationship between the concentration of a substance in a solution and
the amount of light it absorbs.
A=ε⋅c⋅l
A is the absorbance of the solution, which is a measure of the amount of light
absorbed by the substance.
ε (epsilon) is the Molar Absorptivity or Molar Absorption Coefficient. This is a
constant that is specific to the substance being analyzed, the wavelength of light used,
and the units of concentration.
c is the Concentration of the substance in the solution,
l is the Path Length of the sample, which is the distance the light travels through the
solution, usually measured in centimeters.
 Photodiode are used as detectors which generates current ot voltage when light is
incident on it.
 From the absorbance and wavelength curve required number of wavelengths pairs are
selected for temperature or concentration measurement. (There to measure vibrational
temp and conc, we take two wavelength pairs)
 These wavelengths pair are calibrated to find the parameters
 TDLAS produce 2d temp and concentration maps at kHz frequency
 This method can be used for detection of dynamics of short living species in NTP and
also allows to determine the gas phase temperature.
Take Home msg:
 To measure Rotational temp and electron temp – OES
 To measure Vibrational temp – TDLAS
 Conc of species – FTIR
 CONC of short living species or specific species – TDLAS
 To analyze the catalysts used in plasma aided reaction - DRIFTS
Lecture 7
Ultrasound: Ultrasound waves are characterized by their high frequency, beyond the upper
limit of human hearing (considered to be 20,000 hertz (20 kHz)). It typically falls within the
range of 1 megahertz (1 MHz) to 20 megahertz (20 MHz).
Applications of ultrasound:
 Submarine below sea level to ships above sea contact
 Dog whistle
 For organ imaging and scanning purposes in medical files
In Micro flow there are problems like:
 Weak convective mixing
 Solid handling issues like clogging
Now,
i. Low frequency ultrasound:
 Generate cavitation micro bubbles which intensifies the mixing, which in
turn improves interface mass transfer
 They also break up agglomerates and detach particles from the reactor
surface
ii. High frequency ultrasound:
 Produce standing waves - stationary wave patterns formed by the
interference of two waves that are traveling in opposite directions
 Acoustophoretic effect - phenomenon in which objects or particles in a
fluid experience a force as a result of exposure to acoustic (sound) waves.
This force can move or manipulate particles within a fluid medium
 Acoustic streaming: also known as the Rayleigh streaming, is a
phenomenon in which the oscillation of fluid in response to high-intensity
acoustic waves results in the generation of a steady, unidirectional flow or
current within the fluid.
 In total high frequency wave helps in enhancing mixing via acoustic
streaming and also helps in displacing particles via acoustophoretic effect.
This Utrasonic and microfluidic device combination system consists of the elements below:
i. Signal generator
ii. Power amplifier
iii. Transducer – Which converts this electrical signal into mechanical vibrations
(Sound waves). There are three types of transducers:
 Gas-driven transducer
 Liquid driven transducer (Mostly not used or not possible)
 Electromechanical transducer (Mostly used and easy to use)
iv. This ultrasound produced id fed into the microfluidic device
Piezoelectric effect
i. The direct piezoelectric effect refers to the generation of an electrical charge or
voltage in response to mechanical stress or deformation applied to a piezoelectric
material. When mechanical pressure or stress is applied to a piezoelectric material,
it causes a change in the material's internal charge distribution, which leads to the
separation of positive and negative charges, resulting in an electric potential
difference or voltage across the material.
ii. The converse piezoelectric effect is the reverse of the direct piezoelectric effect.
It involves the deformation of a piezoelectric material when an electric field is
applied across it. When an electric field is applied to a piezoelectric material, it
causes a change in the material's internal crystal structure, resulting in mechanical
deformation, such as stretching, compressing, or bending. This mechanical
deformation produces sound waves.
Thus, here we use the piezoelectric transducer which follows converse piezoelectric effect to
produce the ultrasonic waves.
Specifications
i. Low frequency Ultrasound
 Frequency – 10 kHz to 100 kHz
 Wavelength – 100 mm to 10 mm
 Helps via cavitation
ii. Transition range
 100 kHz to 1 MHz
 10 mm to 1 mm
iii. High frequency Ultrasound
 1 MHz to 1 GHz
 1mm to 1 Microns
 Helps via standing wave, Acoustic streaming and acoustophoretic effect
iv. Cavitation bubble size – 10 micron to 100 micorns
v. Milli- channel size – 1 mm to 10 mm
vi. Microchannel size – 1 microns to 1 mm

Low frequency and Cavitation effect

What happens?
 Initially the bubble form
 It then grows in successive cycles
 Then at one point it reaches an unstable size
 Then it collapses violently releasing large amount of energy temp upto
5000C and pressure – 2000 abs
Factors which influence cavitation are:
i. Frequency
ii. Power intensity
iii. Temperature
iv. Gas (Heat capacity)
v. Liquid properties
vi. Solid
Once the bubble will burst when the interior of the cavity almost release energy with temp up
to 5000K and Pressure 500 MPa. In the interior of the cavity radical formation happen,
pyrolysis reaction takes place and molecular disintegration also happens. All these will lead
to the bubble collapse.
Now when the bubble collapse because of the energy released a temperature and pressure
gradient is developed in the gas-liquid interface. Because of these radical reactions takes
place and thermal break down happens in this interface. Thus, leading to formation of shock
waves towards the solid surface.
Now in the bulk region (Liquid) fast quenching of this temp takes place. But it will
experience intense shear stress due to this wave.
Low frequency ultrasound:
Stable cavitation – Volume oscillation and Shape oscillation (Not required as they pose
confinement threat)
Transient cavitation – required for good mixing and mass transfer. When the bubble collapses
it led to temp and pressure development, more radical formation and thus reaction
enhancement
Smaller microchannel may lead to weaker cavitation effect due to confinement. Like the
bubble wont break as they get confined in limited space. This will in turn possess a large
viscous resistance to the flow of fluid in the microchannel and this leading to hydrodynamic
pressure drop.
Strongest cavitation with line resonance radius, if the channel Dia is more that this radius
effective cavitation can be seen. Because this radius tells about the maximum radius a bubble
can reach.
Critical size for effective cavitation comes in mm range not in microns range
Hydrostatic cavitation Ultrasound cavitation
Low pressure pulse Periodic acoustic excitation
Compression periods ranging from 1 to 50 UC Transducer 20 to over 1 MHZ
ms

Diagnostics methods and their function imp

 Lecture - 8
Disadvantages of Batch Manufacturing
 Many individual steps – requires high building footprint
 Quality can be only assessed at the end of the reaction. So, chances are like the whole
batch may get rejected and wasted.
 Scaling up is not easy because its Time consuming since cleaning time is high and
costly
 Fast exothermic reaction is difficult to control in batch reactors
Advantages of Batch manufacturing:
 Versatility: Easy for customization of products by changing the recipe a little bit
 Flexibility: Same reactor can be used to produce different reactions
Advantages of Continuous manufacturing:
 All the steps involved in one streamline process
 Quality check can be done in between without interrupting the process
 Saves more time compared to most of the batch process
 Scale up is easy
 Reduce building footprint
 Can handle fast exothermic reactions
Disadvantages of Continuous process:
 High initial investment
 Complex start up and shut down
 Limited flexibility
Now how does Continuous manufacturing with micro reactors will help than in conventional
reactors?
 Enhanced Mass transfer (Sherwood no high)
 Enhanced Heat transfer (Nu no high)
 High reproducibility
 Multistep flow sequences
 Automation
 Safety
 Scalability
 Favors gas-liq reactions
 Control exothermic reactions
 Easy to study reaction kinetics
 Minimizing huma error
Importance of Mixing
More effective the mixing, more rapidly the reactants will be bought into contact with each
other and thus more desired product will be formed. Therefore, for more rapid mixing the
mixing time should be less compared to reaction time. That is mixing rate should me more
compared to reaction rate.
Now Da(II) = (mixing time)/(reaction time) or =(reaction rate)/(mixing rate)
For Da(II)>1 ie the reaction will be more controlled by mass transfer and will lead to by
product formation (Disguised chemical selectivity)
Da(II)<1 – eliminates mass transfer effect. Reaction rate-controlled regime. Desire product
formed in large quantities (Favorable contition)
So now what to do id Da(II)>1. It can be made <1 in three ways:
i. Decrease the reaction rate:
By lowering the reaction temperature, the reaction rate is decreased is made
slower than the mixing rate. That is reaction time < mixing time
ii. Increase the mixing rate
Micromixing: speed up the mixing rate through shortening of the diffusion path
length (y=0t to h) (we know diffusion time is strongly dependent on diffusion
length) So small lengths, fast diffusion fast mixing lower mixing time and thus
Da(II)<1
iii. Do both decrease reaction rate and increase mixing rate
Dilute the reaction concentration, so lower concentration results in lower
reaction rate and mixing can be done fast so higher mixing rate and thus Da(II)<1
Note: The problem with lowering reaction temperature is it is not always possible because
sometimes it may lead to solidification.
Importance of Dispersion
Flow in microreactor is generally laminar – plug flow will be good for micro reactor
Now consider a new dimensionless number
Bodenstein number (Bo) = Convection dispersion/axial dispersion
For a plug flow in micro reactor the Bo>100. (favorable condition) to attain his condition the
tube diameter should be less than 800 microns. When the tube Dia is less and we have high
residence time (length/superficial velocity) we get Bo>100and thus good conversion.
Now for reaction first check Da(II)<1 and Bo>100. If so proceed with the reaction.
Earlier we saw what can be done to make Da(II)<1. Now what if Bo<100. In that case you
can introduce segmented flow in the micro reactor
Segmented flow – the toroidal circular patterns in it minimizes the dispersion and make the
microreactor to act as a ideal plug flow reactor as the communication between individual
segments is minimized. When it comes for segmented flow micro reactors gives high mass
transfer coefficient and high surface to volume ratio compared to other conventional reactors.
Flow Vs Batch
  Now consider Catellani reaction. (see slide 13). If this reaction in sone in batch
process it is a five-step process and take more time (about 6hrs) but in continuous
process it only takes less time (about 2hrs) as it is a single step process.
 Now for a continuous flow Catellani reaction if we use segmented flow in a micro
reactor set up it decreases the dispersion and increases the mixing rate and thus more
conversion.
Note: Here reaction time if 2hr so the convection time should be >2hrs for efficient
convection. Ie Da(I) = (convection time /reaction time)>1 for good conversion
 Note: In ca continuous catellani reaction set up a backpressure regulator is used to
shrink the bubble size in segmented flow since reaction takes place in the slug
decreasing the size of the bubble helps in increasing the conversion
 Also, for the same catellani reaction it was seen that flow process gives 66% yield
within 2hrs whereas batch process gives 12% yield within 6hrs.
 When it comes to phase transfer catalysis if conducted in batch process for better
conversion is enhanced by stirring. So, for that we can increases the stirring rate but it
will lead to formation of vortex which will again impede the conversion. Now with
flow process when we use segmented flow there is no requirement of stirring since the
flow pattern provide effective mixing. Also when the same flow process is done in
microreactor with segmented flow, for a fixed residence time as the average surface to
volume ratio increases the conversion also increases.
Suitability of reactions
Type A reactions: very fast, reaction time<1s, Mixing controlled
Type B reactions: rapid, reaction time: 1s to 10 min; Kinetically controlled
Type C reactions: slow, reaction time > 10 min; safety and quality issues
Note: Micro reactors are more concerned about type A. It is not used in type B and C
Note: For type A reactions with lower residence time if we decrease the reaction temperature,
we can get good selectivity.
Safety In Micro Reactor
 Can avoid explosion. The power of an explosion is directly proportional to the mass
of explosive mixture in the reactor with the power of 1/3. So, for a micro reactor the
mass handled will be less compared to other conventional reactors. Also, in micro
reactor the initiation reaction for an explosion can happen but it is not possible for the
propagation to take place (Free radical formation does not happen in micro reactor)
 Micro reactors cannot be considered as completely safe but the range of safe
operating conditions can be substantially increases there is reduction of explosion
regime in micro reactors that is the upper explosion limit is reduced in this case
 It is been proven that the hazardous intermediates which are generated in between are
subsequently reacted away in the follow up reaction.
Multistep synthesis
In batch process there is a need of intermediate purification for this kind of reactions but not
required in the case of continuous process.
Characteristics of multistep synthesis:
 Steps without intermediate work up
 Improves efficiency
 Facilitates flow chemistry
 Not always feasible
 Reaction should be created in such a way that by products and excess of reagents
from upstream process can be tolerated by the downstream ones
 Can inject scavengers (substance added to improve purity), reagents and catalysts at
fixed position which is good when it comes to preparation of small amount of
product, Here the cartridges need to be periodically replaced.
 Use of miniature unit operations like micro extraction, micro distillation, micro gas
liquid separation (in this case when separation happens without gravity affinity
separator are use like parallel flow between a hydrophobic and hydrophilic material-
so there flow rate should be properly maintained because if flow rate increases then
separation not possible by affinity)..

Clogging of Micro reactors

 Clogging happens when solubility of product more than that of reactant
 Ultrasound technology can be used to get rid of clogging
 Clogging mechanism two way; Bridging (Completely closing the flow path) and
constriction (Partially reduced the flow cross section area)
 Bridging can be avoided if we can reduce the number of bends in the micro reactor
 In presence of the acoustic irradiation, it reduces the size of the particle
 Also, to prevent clogging flow velocity increased can reduce wall deposition. But if
flow velocity increased the residence time will decrease which will also affect the
conversion.
 Ultrasound bath can be used in case protonation solvents are used which will in turn
lead to salt formation and thus to clogging so, this ultrasonic bath provides a the
radiation all over the surface of the micro reactor which decreases clogging.
 Other solution to prevent clogging are:
i. Immobilization of scavengers, catalyst and reagents
ii. Use of polar solvents which dissolve salts
iii. Biphasic conditions – both polar and non-polar solvent used. The reaction
takes place in non-polar solvent and the product form polar
iv. Use of gas-liquid flow
v. Encapsulation of the solid-forming reaction in droplets (reaction takes place in
droplets which are separated from the wall)

Photochemistry
 Photochemistry is a branch of chemistry that deals with the study of chemical
reactions and processes that are initiated or influenced by light
  It cannot be carried in batch process as the light penetration depth is only to a few
microns.
 Most of the cases Hg bulb or LED light are used as light source
 A typical design for continuous photochemical reactors is the Tubular design. Tubes
need to be transparent and UV permeable since we use the light source
 UV light – Most of the organic molecules get excited by absorption of UV light
because it has high energy content.
 But when you consider solar reactor, it mainly comprises of visible light range (42%)
and less UV light (5%). So, it is useful if the particles absorb visible light. In order to
achieve that we need to do photoredox catalysis.
Photoredox Catalysis
 It allows the absorption of visible range wavelength light and creates active sp which
can participate in the reaction.
 Advabtages of doing photoredox catalysis are:
i. Only requires cheap and low energy light source (LED or Sunlight)
ii. New opportunities in organic synthesis
 Typical photoredox catalysis happen like:
i. First the photoredox catalysts is activated by the light ( blue LED/Sunlight)
ii. The activated catalyst oxidizes the substrate
iii. Followed by reduction of the supporting reactant
 Scale up problems for photoredox catalysis are:
i. In batch process due to limited penetration depth of light it requires higher
reaction time and higher catalyst loading
ii. Catalyst closer to the outer wall will have higher reaction rate considered to
the catalysts in the interior
iii. Penetration cannot happen after 500 microns dia, so channel dia should always
be less than 1mm
iv. Variability in the light source performance with time
v. Variability of the distance to the source
How does Microflow chemistry helps in photoredox catalysis?
 Allows for easy scale up
 Helps to attain a uniform irradiation for the reaction solution
 Thus, lower catalysts loading, shorter reaction times and less side products
 Enhanced heat and mass transfer
 High surface to volume ratio
 Safety of operation when using exothermic or explosives or while using toxic reagents
Trifluoromethylation of arenes via photocatalysis (Photocatalytic C-CF3 adiition)
 Here photocatalysis helps in fast CF3 addition because arene are conjugated molecule
(ie one single bond between two double bond) which can easily absorb blue light and
thus radical formation will be easily done for CF3 addition
 When combined with the reaction happening in microstructure it provides more
advantages as discussed before.
Stern-volume quenching experiments
 During photocatalysis so many free radicals will be formed.
 These free radicals are absorbed by the quenching agents which hinders the overall
reaction
Photocatalytic C (sp3) oxidation
 Advantages over conventional oxidations are:
i. Inexpensive catalyst used (TBADT – mediator to absorb light)
ii. Scalable
iii. Simple reaction conditions
iv. Chemo selective
v. O2 is the required oxidant
vi. Sustainable
 Note: as I increase the residence time and the TBDAT conc by a bit the yield also
increases
 UV light of 365nm was useful. No conversion for 45 nm and low conv for 400 nm
 Here when the substrate cost is less, we can use benzophenone instead of TBADT as
it is less costly. But in this case, we will get only lower yield but it reduces the cost by
so much. Also, TBADT requires pure oxygen but benzophenone only requires air. So,
selection depends on the substrate cost and the yield you want
Solar Photochemistry
Issues associated with solar photo(micro) reactors:
 Requires direct sunlight
 So, for that we require sun tracking system and refractors to direct sunlight. Which
will lead to a complex setup
 It is wavelength dependent
 Red light has higher wavelength than blue light
 It absorbs red light but u have more blue light in the solar spectrum.
 So, u can use organic dyes to absorbs blue light and emit red light so that we can
make use of full solar light spectrum
 Using organic dye will also increases the conversion
 Photo microreactor – work under main principle – Fluorescence – phenomenon in
which substance absorb shorter wavelengths and emit larger wavelength.
Flow Electrochemistry
 Advantages:
i. Use of green electricity – sustainability
ii. Resource efficient – no need catalyst and toxic oxidizing and reducing agents
iii. Energy efficient – room temperature activation possible
iv. Redox chemistry
 Disadvantages:
i. Power supply required
ii. Initial cost very high
 iii. Good electrodes require and thus maintenance required
 Electrochemical cell or galvanic cells- generate electric current in which 2 electrode
reaction occur spontaneously (Used in batteries)
 Electrolytic cell – reaction occur when external voltage is applied that is electrical
energy converted to chemical energy
 Anode – oxidation occurs – lose of electron – positively charged
 Cathode – reduction occurs – gain of electrons – negatively charged
Challenges in electrochemistry
i. Ohmic drop – voltage drop between two electrodes
 Voltage drop is influenced by:
a. Conductivity of solution- more conductivity more ohmic drop
b. Relative distance between electrodes – larger distance more ohmic
drop
c. Magnitude of current – high current more resistance more ohmic drop
 It can be controlled by adding supporting electrolytes which contains one
common ion with the main electrolyte. Eg: KOH used as supporting
electrolyte for electrolysis of water
 Shoretr distance – less ohmic drop – brings microreactor into picture –
thus lower amounts of electrolyte required
ii. Solid precipitation
 Deposition of materials on electrode will further increase the resistance
iii. Mass transfer at electrodes
 Electron transfer occurs at eletrodes – undesirable situation
 If reaction is taking place at electrode – liquid interface it can be controlled
by reducing current which in turn reduces the reaction rate.
 The larger the current the faster the reaction (Faraday’s Law)
 Note:
  Taylor flow is not useful for electrochemistry because of the sudden
potential jumps it can provide and loss of electrode contact with electrolyte
Benfiits of micro reactors in electrochemistry
i. Easy scale up
ii. Lower amount of electrolyte
iii. Reduce ohmic drop
iv. Enhanced heat and mass transfer – high surface to volume ratio
v. Faster reactions – increased electrode surface
vi. Safety operation

Faradaic efficiency:

N is the number of electrons transferred,

F is the Faraday constant,
I is the current observed in the experiment,
t is the duration of the experiment.
If faradaic efficiency is 100% for a particular reaction, then only one process is occurring at
an electrode. That is not possible usually more than one process happens at an electrode. So
eff<100% always.

Electrode design
i. Parallel flow field
 reduces pressure drops and increases efficiency but can accumulate small
droplets of water to enhancing the chances of blocking the flow
ii. Serpentine flow field
 rapidly drain the cell products but due to large area plate, flow channel too
long and hence high pressure drop.
iii. Interdigitated flow field (But most favorable one)
 the main difference being the flow penetrates through the diffusion layer.
Hence chances of destroying the catalyst material is higher.

Note: Higher voltage and higher current density means higher reaction rate and higher yield

Lecture 9
The analytical devices like UV, NMR, HPLC, IR etc. produces the input for the Process
analytical techniques which consists of the measuring device and control loop.
Note: most of the analytical techniques doesn’t like two phase flows they prefer to analyze
single phase flow.
Sampling for analysis can be done in three ways:
i. In-line sampling – continuous flow and continuous analysis
ii. On-line sampling – non- continuous flow or intermittent analysis
iii. Off-line sampling – sperate aliquots are taken and analyzed
Both inline and online involves automatic sample preparation where as off-line involves
manual sample preparation

Analytical techniques
i. Destructive techniques (Sample not possible to recover)
 Mass spectrometry (MS)
 GC-FID – Gas chromatography flame ionization detector
 LC-MS
 XRD
ii. Non-destructive techniques (Mostly preffered)
 UV/VIS
 IR
  NMR
 Refractive index
 HPLC-DAD - High performance Liquid chromatograph with Diode Array
Detection
UV-VIS spectroscopy
For electrons to do transition from lower energy level to upper energy level it requires energy.
This energy can be obtained by absorption of light. These light wavelengths fall under the UV
and Visible range. So once the transmitted light is detected we can analyze the content in the
solution. But for this transition to happen they required chromophores (double or triple bond
i.e., free orbit is required), one of the major disadvantages of UV-VIS.
Now if in a UV-VIS spectrometer we need more volume of sample for analysis which will be
placed in the quelet. This quelet will also have a lot of dead space and in case of quelet the
optical path is long so the absorbance will be less. Thus, small sample space like a Z-flow cell
can be used so that optical path is reduced and proper absorbance can be calculated.
UV-VIS follows the equation;

Advantages of UV:
i. Non-destructive, Inline
ii. High sensitivity (But depends on path length and the E0)
iii. Low cost
iv. Quantitative analysis
Disadvantages of UV-VIS:
i. Not compatible with 2 phase flow
ii. Need chromophores (Functional groups which absorbs UV-VIS region)
iii. Easily saturated (Absorbance > 1)
iv. Low selectivity
Note: Sensitivity in this case is the ability to measure lowest possible amt of substance and
selectivity is ability to measure only substance of interest not affected by presence of other
substances
UV-VIS helps in determining the color, concentration and the residence time distribution
Narrower the RTD curve – characteristics of plug flow
Broader the RTD curve – characteristics of Laminar flow
As the tubing diameter decreases or residence time increases or the viscosity decrease there
RTD curve becomes narrower
Application: UV-VIS helps to study very fast reaction with double bond eg: polymerization
reaction (More wide the RTD curve more the polymerization)
UV-Vis is not suitable in case of Taylor flow

Infrared Spectroscopy
Allows to find the functional groups in the molecules
Vibrational transitions fall under IR range. These vibrato=ion are of two ways stretching and
bending.
The IR source does not directly hit the sample. It goes and hit a ATR crystal (Attenuated Total
Reflection Crystal) like diamond.
For IR, measurement in gas phase is easier (we get narrow peaks) compared to sample in
liquid phase (where more wider peaks are seen – can overlap)
Advantages of IR
i. Non-invasive (doesn’t interfere with the system)
ii. Non-destructive, Inline
iii. Quantitative but calibration required
iv. Better specificity than UV/VIS – more samples can be measured.
Disadvantages:
i. Polar groups required
ii. Crystals are costly so if any organic deposits happens, they need to be replaced.
iii. Relatively expensive than UV-VIS
iv. Low sensitivity
v. Minimum wavenumber difference 100 should be there in the table for
identification

NMR Spectroscopy (Nuclear Magnetic Resonance)

Through IR part of structure can be determined NMR gives entire info about it. Here the
transition comes under the radio wave spectra.
NMR is based on the inherent property of certain nuclei, known as nuclear spin. Nuclei with
non-zero nuclear spin, such as hydrogen (protons) and carbon-13, generate magnetic
moments when placed in a magnetic field.
When a sample containing nuclei with non-zero spin is exposed to a strong external
magnetic field, the nuclei align themselves with the field. Radiofrequency (RF) pulses are
then applied to the sample, temporarily tipping the nuclear spins away from the magnetic
field direction. When the RF pulse is turned off, the nuclei return to their aligned state,
releasing energy in the form of electromagnetic radiation at their resonance frequency. This
radiation is detected and used to create an NMR spectrum.
Four ways of NMR reaction monitioring
i. Static (in NMR tube /offline sampling)
 Simplest
 No special equipment required
 Deuterated solvents required
 Every 2 s u get one scan
 Takes the largest time for analysis
 Classical equation can be used
ii. Flow cell (online monitoring) (more favourable)
 Special flow tube (probe) required
 Specific equation needed
 Mixing cannot be saturated
 Can avoid deuterated solvent which is required in all the other three cases
 It is scalable which is not in the other three cases
iii. Stop-flow (flow cell)
 Used for faster kinetics (2.5 ms to 100 ms)
 Very small probes are required
 Specific equation needed
 Fast kinetics cannot be studies in continuous flow. So stop flow is required
 Fastest way of monitoring
iv. Rapid injection (in NMR tube)
 Custom probe or inserts
 Fast kinetics (40 ms – 1s)
 Not useful for fast reaction but still useful to study A type reaction
 Classical equation can be used
Tow types of magnet high field (Stronegr magnetic field – more separation – narrower ans
sharp peak) and benchtop (weak magnetic field – poor split)
Advantages:
i. Quantitative
ii. Great specificity
iii. Non-destrcutive and in-line
iv. Multiple in-line monitoring
v. Automation
Disadvantages:
i. Low sensitivity (nucleus dependent)
ii. Incompatible with multiphase flow
 iii. Limited range of flow rates
iv. Need of deuterated solvent (H2 should not be present in the solvent- as it may
overlap) (for high field magnets)
v. Low resolution in case of bench top magnets
vi. High field magnets costly
Mass Spectrometry
 Measures Mass to charge ratio (m/q)
 It allows us to measure the masses of the atoms and molecules
 Most important peak is the molecular ion peak which can provide the details of the
mass of molecule
 Spectrometry involves the mesurement of the electromagnetic radiation.
 Spectroscopy is the study of the electromagnetic radiation with which they interact or
produce.
 Advantages:
i. High sensitivity (Detects unstable intermediates)
ii. Good specificity
 Disadvantages:
i. Requires dilute sample
ii. Destructive due to ionization
iii. Relatively expensive

Need for analytics in continuous manufacturing:

 Improve production quality and consistency
 Real time release testing
 Prevent wastage
 Multi-variable analysis of multiple quality attributes in parallel
 Increase automation and safety

Lecture – 10
Advantages of automation in flow:
i. Remote-controlled experiment
ii. Improved productivity
iii. Better parameter understanding
iv. Self-optimization
v. Increased reproducibility
vi. Potential to integrate machine learning
Disadvantages of Automation in flow:
i. High initial cost
ii. Technical complexity
iii. Proper maintenance required or else may lead to more downtime
iv. Lack of flexibility – specific task assigned
Challenges faced by automation in flow
i. Increasing flow rate from inlet to outlet
ii. Axial dispersion – automation will not eliminate axial dispersion
iii. Material construction
iv. Solids handling
Auto sampling and analysis (one automation application)
In auto sampling the main two processes are: purification (removal of impurities, done by
techniques likes chromatography, crystallization and etc.) and quantification (determines the
concentration or the amount of a specific compound within the sample eg. Evaporative light
scattering detector).
ELSD - operates on the principle of converting the eluting analytes (compounds separated by
chromatography) into small droplets through nebulization. These droplets are then
evaporated, and the remaining solid particles scatter light, which is detected and quantified.
The intensity of scattered light is proportional to the amount of analyte present.

Reaction Optimization (another application of automation)

 Reaction optimization means systematically varying and fine tuning reaction
conditions to achieve the best possible outcome.
 Self-optimizing reactors mostly have single step synthesis.
 For optimization algorithms are very important
 Good algorithm should only use minimum number of steps
 Objective function can be arbitrarily choose based on the need of the optimization
process (eg: reaction yield)
 Two types of algorithms:
i. Steepest descent (mostly useful in finding maximum)
 Principle: The steepest descent is a first-order optimization algorithm
that uses the gradient (first derivative) of the objective function to
 guide the search for the optimal solution. It moves in the direction of
the negative gradient to reduce the function value iteratively.
 Application: In reaction optimization, you can use the steepest descent
method to adjust one reaction parameter at a time, such as temperature
or reactant concentration, based on the calculated gradient. By
repeatedly making small adjustments in the direction that minimizes or
maximizes the reaction yield (depending on your objective), you aim
to converge to the optimal conditions.
ii. Conjugate gradient (Fast algorithm than the one above)
 Principle: Conjugate gradient is also a first-order optimization method that
aims to find the minimum or maximum of a function, but it incorporates
information from previous iterations. It combines gradient information with
conjugate directions, which can lead to faster convergence, especially for well-
conditioned problems.
 Application: In reaction optimization, the conjugate gradient method can be
applied similarly to steepest descent but with the advantage of using more
sophisticated search directions. It can be particularly useful for complex
reactions with many variables and interactions. It iteratively updates the
reaction conditions, taking into account previous steps, which can lead to
faster convergence to the optimal conditions.
Machine Learning
Definition: A collection of data-analytical techniques aimed at building predictive models
from multidimensional datasets. A discipline in computer science wherein machines are
programmed to learn patterns from data.
Features (=descriptors) = measurements: raw data or calculated data or mathematically
transformed data
Labels = Output of the model (e.g. yield, selectivity, reaction conditions)
The missing link between features and labels is the aim of ML!

Two main errors in Machine Learning:

1. Overfitting: parameters of the model are fit so specifically to the training data that it does
not have any predictive power outside the test data.
Cause: Model is too complex
Solution: Increase the training dataset; decrease the complexity of the model by removing
irrelevant features (Feature selection)
2. Underfitting: Model does not accurately predict the training data
Cause: model is too simple
Solution: Increase the complexity of the model
Deep Learning (artificial neural networks) (A Machine learning method)
 Neural networks transmit information through layers of weighed, interconnected
computational units (aka neurons)
 The more hidden layers, the deeper the neural network
 Complex hidden layer, difficult to understand the rationale behind it
 Data hungry
 Expensive (cloud computing)