INDUSTRY 4.

0: AI IN BIO-PROCESSING &
3-D BIO-PRINTING

Dr. Shirsendu Mitra

Assistant Professor
Chemical Engineering
School of Technology
Pandit Deendayal Energy University Gandhinagar

Dr. Shirsendu Mitra LECTURE 24 1

 OVERVIEW

 Quick Recap
 Introduction
 Implementation of AI
 Applications of AI
 3D Bioprinting
 Application of 3D Bioprinting

Dr. Shirsendu Mitra

UNIT 4 2
Industrial Biotechnology Revision: Video 1

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 INTRODUCTION

• Artificial intelligence (AI) refers to the simulation of human

intelligence in machines that are programmed to think like
humans and mimic their actions. The term may also be applied
to any machine that exhibits traits associated with a human
mind such as learning and problem-solving.
• The ideal characteristic of artificial intelligence is its ability to
rationalize and take actions that have the best chance of
achieving a specific goal.
• AI can perform quality control, shorten design time, reduce
materials waste, improve production reuse, perform predictive
maintenance, and more. AI can be used in many ways to make
production more efficient with faster output and less waste.

Dr. Shirsendu Mitra

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 CLOSED LOOP LEARNING

• The closed-loop learning in bioprocess development

involves the control of experimentation devices and
operations, data processing and decision-making on
new experiment design.
• The Artificial intelligence platform for bioprocess
development based on the closed-loop learning
approach intents to drive the experimentation
devices to perform defined initial experiments and
drive the analytical devices to detect the data after
the experiments are completed.
• Then it will pick up the data from the analytical
devices and perform data analysis that turns the raw
data into variable values such as protein
concentrations, and carry out process evaluation
based on the design objectives.
• After evaluation of the design solutions, it will
decide to stop or continue to design the next round
experiments for further optimization.

Dr. Shirsendu Mitra

 FRAMEWORK OF AI

The framework of AI consists of five different components:

1. Data & knowledge base

2. Sequential design method

3. Execution of experiments

4. Assay execution

5. Data treatment

Dr. Shirsendu Mitra

 FRAMEWORK OF AI

• Data & Knowledge:

It is base is a database designed to store and accumulate the data of previous
experiment results. It will have the capability of providing supporting data for
experiment design such as operating area, input variables and output variables.
• Sequential Design Method:
It is a software element that has the experimental design algorithms established,
capable to design a batch of experiments compatible with microscale devices,
then translate the experiments into detailed simple tasks, finally write the
command scripts for these tasks that can be recognized by experiment devices.
It also performs evaluation of returned experiment data based on the pre-
defined research objectives, makes decisions on discovered, the new knowledge
will be added into knowledge base. If not, further validation experiments will
be send to Execution of Experiments & Assay element to execute.

Dr. Shirsendu Mitra

 FRAMEWORK OF AI

• Execution of Experiments & Assays:

These are hardware associated with the experimentation to deliver the pre-defined
tasks. IA should be designed to drive this hardware at right time through
communication.
• Data Treatment:
It is another software element that processes raw data, translates raw data into the
format that has biochemical meanings. For example, it translates uv absorption data
into protein concentration. A key element in the closed-loop learning is the
objectives of the activity, which needs to be defined beforehand. To deliver a
process design activity, the objectives must be defined and formulated
mathematically by the users. Typical design objectives include purity, yield, cost,
productivity or combination of them. This will help the biochemical engineers
focus on their goals.

Dr. Shirsendu Mitra

IMPLEMENTATION OF AI

Dr. Shirsendu Mitra

 IMPLEMENTATION OF AI

• Amgen is piloting a process using artificial intelligence (AI) that has the potential to
greatly enhance its ability to trend and find patterns in manufacturing deviations and
to prevent their recurrence.
• The AI tool will replace a manual, labor-intensive process with one that can look
across large data sets and find correlations between obscure signals and events which
the previous system could have missed.
• In creating the AI tool, the team used agile software development. Agile development
is an iterative approach under which requirements and solutions evolve through the
collaborative effort.
• It involves an incremental development strategy, meaning each successive version of
the product is usable and each builds upon the previous version by adding user-
visible functionality.
• Because the deviation reports which Amgen calls non-conformance (NC) reports are
documents containing mostly text & thus the project team decided to employ an AI
tool called natural language processing (NLP) to examine them.
• NLP provides a way for computers to analyze, understand, and derive meaning from
human language, including not only words but also concepts and how they are linked
together to create meaning.

Dr. Shirsendu Mitra

DATA SCIENCE PARADIGM

Dr. Shirsendu Mitra

 DATA SCIENCE PROCESS

• For a large company manufacturing, purifying,

and packaging biotech drugs, a huge amount of
diverse data is generated, not all of which is
digitized.
• The focus is on the application of data science
specifically in quality operations, using a data
science process. The process begins with a
question, after which the team gets the data;
explores, models, and visualizes it; and then
interprets it
Dr. Shirsendu Mitra
 APPLICATION

• The use of Artificial Intelligence in biotechnology and related

applications play a crucial role in managing biological
processes, boosting drug production, handling supply chains,
and taking care of the pool of data for this industry.
• Leading biotech companies are investing in advanced AI tools
to:
i. Analyze research data
ii. Accelerate vaccine development
iii. Classify the target market and demographic
iv. Identify the right ingredient to produce the vaccine

Dr. Shirsendu Mitra

 APPLICATION (continues)

Other major application in which AI is growing are:

• Fermentation
• Tissue engineering and regeneration
• PCR technology
• Nanobiotechnology
• Chromatography
• DNA sequencing
• Cell-based assay

Dr. Shirsendu Mitra

3D BIOPRINTING

Dr. Shirsendu Mitra

3D Printing

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3D Bioprinting

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 3D BIOPRINTING

• 3D Bioprinting is a form of additive manufacturing that uses cells and other

biocompatible materials as “inks”, also known as bioinks, to print living
structures layer-by-layer which mimic the behaviour of natural living systems.
• The geometry of a 3D bioprinted structure is more similar to that of a naturally
occurring biological system than an in vitro study performed in 2D, and can be
more biologically relevant.
• It’s used most commonly in the fields of tissue engineering and bioengineering,
and materials science. 3D bioprinting is also increasingly used for
pharmaceutical development and drug validation, and in the future will be used
for medical applications in clinical settings – 3D printed skin grafts, bone grafts,
implants, biomedical devices, and even full 3d printed organs are all active
topics of bioprinting research.

Dr. Shirsendu Mitra

 3D BIOPRINTING PROTOCOL

• 3D bioprinting starts with a model of a structure, which is recreated layer-by-

layer out of a bioink either mixed with living cells, or seeded with cells after the
print is complete. These starting models can come from anywhere – a CT or MRI
scan, a computer generated design (CAD) program, or a file downloaded from the
internet.
• That 3D model file is then fed into a slicer – a specialized kind of computer
program which analyzes the geometry of the model and generates a series of thin
layers, or slices, which form the shape of the original model when stacked
vertically. Cura and slicer are examples of slicers commonly used in 3D printing.
• Once a model is sliced, the slices are transformed into path data, stored as a g-
code file, which can be sent to a 3D bioprinter for printing. The bioprinter follows
instructions in the g-code file in order, including instructions to control for
temperature of the extruders, extrusion pressure, bed plate temperature,
crosslinking intensity and frequency, and, of course, the 3D movement path
generated by the slicer. Once all of the g-code commands are completed, the print
is done and can be cultured or seeded with cells as part of a biostudy.

Dr. Shirsendu Mitra

 WHY 3D BIOPRINTING

• The greatest importance of bioprinting lies in the resulting tissue-like

structures that mimic the actual micro- and macro-environment of
human tissues and organs. This is critical in drug testing and clinical
trials, with the potential, for example, to drastically reduce the need for
animal trials. When living tissues and organs need not come from
humans, this budding technology offers other massive opportunities.
One example is testing treatment for diseases using artificially affected
tissues.
• The process could also eradicate the headaches associated with organ
donation and transplantation. Apart from the lack of available organs,
the entire process is criticized from a moral and ethical perspective.
Organ replacement is the main objective, but tissue repair is also
possible in the meantime. With bioink, it’s much easier to solve
problems on a patient-specific level, promoting simpler operations.

Dr. Shirsendu Mitra

 WORKING

Dr. Shirsendu Mitra

 WORKING

Several bioprinting methods exist, based on either extrusion, inkjet, acoustic, or laser technologies. Despite
the various types, a typical bioprinting process has a more-or-less standard series of steps:
• 3D Imaging: To get the exact dimensions of the tissue, a standard CT or MRI scan is used. 3D imaging
should provide a perfect fit of the tissue with little or no adjustment required on the part of the surgeon.
• 3D Modeling: A blueprint is generated using AutoCAD software. The blueprint also includes layer-by-
layer instruction in high detail. Fine adjustments may be made at this stage to avoid the transfer of
defects.
• Bioink Preparation: Bioink is a combination of living cells and a compatible base, like collagen, gelatin,
hyaluronan, silk, alginate or nanocellulose. The latter provides cells with scaffolding to grow on and
nutriment to survive on. The complete substance is based on the patient and is function-specific.
• Printing: The 3D printing process involves depositing the bioink layer-by-layer, where each layer has a
thickness of 0.5 mm or less. The delivery of smaller or larger deposits highly depends on the number of
nozzles and the kind of tissue being printed. The mixture comes out of the nozzle as a highly viscous
fluid.
• Solidification: As deposition takes place, the layer starts as a viscous liquid and solidifies to hold its
shape. This happens as more layers are continuously deposited. The process of blending and
solidification is known as crosslinking and may be aided by UV light, specific chemicals, or heat (also
typically delivered via a UV light source).

Dr. Shirsendu Mitra

PRINTING METHOD

Dr. Shirsendu Mitra

 IMPORTANCE

• The greatest importance of bioprinting lies in the resulting tissue-like structures that
mimic the actual micro- and macro-environment of human tissues and organs. This
is critical in drug testing and clinical trials, with the potential, for example, to
drastically reduce the need for animal trials.
• When living tissues and organs need not come from humans, this budding
technology offers other massive opportunities. One example is testing treatment for
diseases using artificially affected tissues.
• The process could also eradicate the headaches associated with organ donation and
transplantation. Apart from the lack of available organs, the entire process is
criticized from a moral and ethical perspective.
• Organ replacement is the main objective, but tissue repair is also possible in the
meantime. With bioink, it’s much easier to solve problems on a patient-specific
level, promoting simpler operations.

Dr. Shirsendu Mitra

 APPLICATION

• Artificial organs are one of the greatest drivers of the technology due to the high
rise of vital organ failure. Availability of 3D printed organs helps to solve organ-
related issues faster and quicker, which is important to patients, their families, and
healthcare systems.
• Development of tissues for pharmaceutical testing, when 3D printed, is a more
cost-effective and ethical option. It also helps in identifying side effects of drugs
and allows recommended drugs to be administered to humans with validated safe
dosages.
• Cosmetic surgery, particularly plastic surgery and skin grafting, also benefits from
the technology. In this particular application, bioprinted skin tissue could be
commercialized. Some 3D printed tissues are already being bioprinted for research
on therapeutic purposes.
• Bone tissue regeneration as well as prosthetics and dental applications.
• There are various other uses and applications of bioprinting, including producing
foodstuffs such as meat and vegetables.
Dr. Shirsendu Mitra
Dr. Shirsendu Mitra
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