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Intro to Biomedical Engineering** - Coggle Diagram
Intro to Biomedical Engineering**
Medical imaging
Motion
problems of motion
Involuntary
Organ motion
eg. cardiac, respiratory
head/body motion
eg. reflex, tremor
Voluntary
head/body motion: discomfort, anxiety
Prevent motion
Firm restraint
a. non invasive
b. invasive
Drugs( common for animals)
a. sedation
b. paralysis
Motion Compensation
Exclude extra data
image registration (image alignment)
gating( collecting data periodically)
Tomography
Energy
Optical photons (optical tomography)
Electric current
RF (magnetic resonance imaging)
MRI
about proton density (the gydrogen density)
X-rays/ gamma radiation
gamma rays
PET
about radioactivity
SPECT
about functions
X-rays
CT
about density
Acoustic (3D ultrasound)
Nanotechnology
Nanotechnology 101
Nano- science : the study of matter at the nanoscale (1-100nm; at least one dimension)
Nano-technology : the application of nanoscale systems: the creation, utilization and characterization of functional structures (materials, devices, and systems) with at least one characteristic dimension measured at nanometer-length, i.e., at the level of atoms, molecules and supramolecular structures.
Nano in greek means ‘dwarf.
One nm = 10^-9 m ~~ 4 times the diameter of atoms
Nanotechnology
Top-down fabrication (breaking down bulk materials)
Bottom-up fabrication(selectively assembling atoms and molecules)
Medical technology
Nanoscale biological principles of molecular self-assembly, self-organization, and quantum mechanics for Quantum computing
nanomaterials&bioelectronics
Bioelectronics
Bioelectronic implants
Bioelectronic wearable
Nanobioelectronics
Biomimicry: same size scale tp biological building block such as protein and nucleic acids
High surface-to-volume ratio: smaller electronic-- more efficiency
Nanomedicine
Used a lot in oncology and diagnostic
Direct interventions in the human body
nanomaterials
General characteristics of nanomaterials
Super small particles (smaller than cells)
Some materials have weird properties(usually optical and physical) when in nanoscale
Very high surface area to volume ratio
When do nanoparticles interact with living cells and
tissues?
in vitro
Culture the cells in the presence of NP
in vivo
Inhalation --- direct delivery to lungs
Skin --- direct delivery into the layers of skin
Ingestion --- oral, through the gut lining, then bloodstream
Intravenous --- directly into bloodstream, via a vein
Intraperitoneal --- abdominal cavity, then diffuse into bloodstream
Intracerebroventricular --- directly into cerebrospinal fluid that circulates within the central nervous system( includes brain and spinal cord)
we need to control what NP attaches to
Coat the surface with polyethylene glycol PEG
Creates a “hydration layer” that prevents protein adsorption (primary solution)
Synthetically create a ‘don’t eat me’ CD47 marker
Mimin the surface of red blood cells and leukocytes (“white blood cells’)
NP larger than 200nm are more likely to activate the complement protein system
What can we do with NP for medicine?
Often NP alone possess limited usability
Primarily:
conjugating/adding therapeutic drugs/ genes
Protective layer from MPS
Conjugating specific targeting molecules
drug delivery
Reason for drug delivery:
Drugs are mostly designed to kill or harm, if not to certain places, may hurt other organs, which is the ‘side effects” that we heard of before
Factors for successful drug delivery
Right place
Right duration
Right time
Right amount( dose)
targeted drug delivery
active
passive
systemic delivery
Gold NP in medicine
surface plasmon resonance effect
Gold NP- photothermal therapy
nanobisensors
Nanotechnology and biosensor: selectivity and sensitivity
Enhanced sensitivity: eg. due to high surface area and efficient electron transfer
Enhanced selectivity: new ways of identifying, interacting and quantifying biomolecules: geometric confinement, quantum effects
Nanoneuroelectrodes /interfaces
Passive interface
Electrodes
Cells interact with with electricity
Implantable electronic devices
Gold nanoparticle
NP-based therapeutic products:
liposomes and polymer-drugs are the two dominant classes, (more than 80% of the total amount)
Polymer-drug conjugates
Liposomes
Problems of the use of liposomes
problem: the dast clearance of liposomes from the blood by phagocytic cells of the reticuloendothelial system, resulting in unfavorable therapeutic index.
2 strategies to reduce this problem:
to increase the accumulation of liposomes in the desired cells, tissues, and organs. (By attaching targeting ligands such as antibodies, peptides, and small molecules (e.g., folate and transferrin) to the liposome surface, targeted liposomes have been developed for differential drug delivery.)
formulate long-circulating liposomes by coating the liposome surface with inert and biocompatible polymers such as PEG. (The polymer layer provides a protective shell over the liposome surface and suppresses liposome recognition by opsonins, and therefore subsequent clearance by the reticuloendothelial system)
NP-based drug delivery
Improves the solubility of poorly water-soluble drugs, prolongs the half-life of drug systemic circulation by reducing immunogenicity, releases drugs at a sustained rate of in an environmentally responsive manner and thus lowers the frequency of administration, delivers drugs in a target manner to minimize systemic side effects and delivers two or more drugs simultaneously for combination therapy to generate a synergistic effect and suppress drug resistance.
Enhanced Photodynamic Therapy Mediated by Gold Nanoparticle:
Requirements of an ideal photosensitizer:
stability in physiological solutions
established physical and chemical properties
minimal dark toxicity
intense absorption of red or near-infrared light that penetrates deeper into biological tissues
tumor-tissue accumulation efficiency
its interaction with the distribution dynamics
effective and long-term free radical and singlet oxygen generation
production and commercial availability that offers the possibility of successfully introducing drugs into the clinical practice, side effects, and elimination kinetics
Technology and Innovation in Disability
Technology program:
prevent
Pregnancy newborn care
Imaging & analytics --MRI & Ultrasound
treat
speech
mobility
Cause
big data
Bioinformatics
Genetics
Registers
Clinical text mining
causal models
In-vivo
Computational (risk and health economics) (preferable than test on baby animal for brain damage)
policy
AI& ML regulation: Artificial intelligences and machine learning regulation
We give the people also the ability to turn the bioelectronics off
Inclusive design
cure
stem cells
Need to control stem cells of what to produce, and where(need to go to specific areas instead of the major blood stream)
3D printed neural tissue
Stem cell delivery
Growth factors
neural interfaces
Mobility & pain
Continence
Touch & proprioception
calculation: vascular resistance
Tissue Engineering
Biomaterials
Types
bioceramics
Advantages: Wear & corrosion resistance, Bioactive/inert, Easy to sterilize
Disadvantages: Mechanical properties is compromised, Not easy to fabricate
polymers
polymer based material
Advantages: Tailorable physical & mechanical properties, Surface modification, Biodegradable, Easy to fabricate
Disadvantages: Leachable toxic compounds, Wear & breakdown, Difficult to sterilize
natural polymer
it’s compatible, but can’t get it from the same sources
biocomposites
biologically derived materials
metals
advantages: high strength, easy fabrication, easy to sterilize
disadvantage: corrosion, metal ion toxicity
decellularization
Composed of native ECM molecules
Biodegradable and biocompatible after decellularization
Properties
mechanical properties
degradation
Biocompatibility
easy to fabricate
Biomolecules
2 types of cell construct
Cellular construct : cells in scaffold -- in vivo implantation
Cell free construct : no external factors -- in vivo implantation (could be much preferable, could avoid complicated complication)
Tissue engineering
3 different types of transplant
Allograft (donor tissue)
Xenograft (animal tissue)
Autograft (patient's own tissue)
Principles of tissue engineering
ways to get the cells
Biopsy
Small pieces + add enzymes to help break down the cell --- leave it for a few days to isolate itself -- get individual cells
2 different stem cells to get differentiate
Pluripotent stem cells
multipotent stem cells
Principle
produces protein and provides function of cells
given tissue reparative properties
living part of tissue
injured tissue + biomaterials/ cells/ biomolecules or all three = repaired tissue
cells : most are water (70%)
Biomanufacturing
Standardizations
Germans -- DIN
Europeans -- CEN
World -- ISO
Regulatory bodies
CE MARK-- EUROPE
US FOOD& DRUG Administration
TGA -- Australia
notified bodies
evaluate whether the product complies with the relevant legislation in force. (speaks to the regulatory bodies)
such as TUV
ISO9001
ISO13485
Case study -- Breast Implants
Bionics and Neuromodulation
Bionic Eyes
Eye- related Diseases
Age-related macular degeneration (AMD)
The leading cause of blindness in over 55s
By 2020 it will affect 3M people in the USA
Retinitis pigmentosa (RP)
The leading cause of inherited blindness
Affects 1 in 3500 in the USA
Approx. 1.5 M affected world-wide
Starts with collapse, and gradually
Attack people in their 20s-30s
Retinal prosthesis location
Sclera - where the most exchange of blood happens, a lot of metabolism taking place, it’s a bunch of blood vessels
Problem: If put in after the choroid, in the sclera where the problem is, it takes a lot of space away from the choroid
Solution: Actually put it in within the perilymph and bones, so that it last longer, with some distance away from neuron.
So that it does not have a chemical reaction with the neuron that changes the environment PH.
1 more item...
Retinal prosthesis location
Direction: from top to bottom
First Bionic Eye
Targeting on Visual Cortes
Problem: Detects the light frequency but not able to form images
How does bionic eyes deal with leak?
Electrode Array: use tin foid to fold around the electrics to increase the frequency.
Microelectronics
Size of ur pinky fingernail
Robust safety features
Parallel simulation capabilities
Focal activation via hexapolar multiplexing
Threshold reduction through Quasi-monopolar stimulation
Reverse telemetry
high compliance voltage for stimulation from the suprachoroidal space
--Phoenix 99- bionic eye
On sheep
On human
The electrode array and the cable went behind the ear, and then go to lab, use the connector to stimulate the electrode array
Since her photoreceptor is gone, need to replace sth for it --- use the camera on her forehead
What did she see?
Not a dot, but complex phosphenes, and then brain helps make sense
Future:
Biomechanics
Computational Modelling
Workflow for Biomed Engineering
Numerical Analysis
Finite element analysis
Required inputs
Geometry
Material Properties
Loads
Boundary conditions
The finite element method (FEM)
Data acquisition
X-ray
A radiograph is an X-ray image obtained by placing a part of the patient in front of an x-ray and then illuminating with a short x-ray pulse. X-ray can pass most tissues in body
Bones contain much calcium which due to its relatively high atomic number
CT:
CT
A combination of many X-ray images taken from different angles to produce cross-sectional (tomographic) images (virtue ‘slices’)
Ultrasound
no radiation, only ultrasound ray
Ultrasound wave are sounds waves with a frequency which are higher than a human can hear(>20,000 Hz)
Ultrasound image also known as sonograms
The sound echoes off the tissue, with different tissue reflecting varying degrees of sounds
MRI
no radiation
Use strong magnetic fields, radio waves, and field gradients to generate images of the inside of the body
Unit Tesla
CT is good for organ and bony details, hard tissue, Higher-density has higher contrast; MRI has no radiation, good at soft tissue
Solid modeling
Segmentation & reconstruction (the keys)
Anatomy & physiology for engineers
Skeleton
Bone
Problems
Endochondral Ossfication
Gout
Osteoporosis
Cancellous (spongy) Bone
Bone remodeling
Trabeculae (interconnecting rods or plates of bone, like scaffolding)
Space filled with narrow
oriented along stress lines
covered with endosteum
Bone cells
Osteoclasts (remove bones)
Osteocytes (sense bone strain and damage)
Osteoblasts (make new bones)
Bone Composition
Phase 1: Organic
Phase 2: Inorganic
Joints
articular joint cartilage
why we need it?
Damage to intervertebral discs
herniated disc
slipped disc
Bone loss
Arthrities
what is it?
60-70 years fully functional
Low friction
Highly resilient
Low wear material
Muscles
six functions of skeletal muscle tissue
Store nutrient reserves
Produce skeletal movement
Maintain body temperature
Maintain posture and body position
Guard entrances and exits
Support soft tissues
Nervous System
Transmembrane potential
5 Main membrane processes in neural
Activities
Action potential
propagates along surface of axon to synapse
is an electrical impulse
3 functional classifications of neurons
sensory neurons
interneurons
motor neurons
Regulatory Affairs
Ethics and regulatory affairs
5 Ethical Theories
used as lens to view problems
Ethical Egoism:
Protect own interest
We would not tell them as this would affect our research outcomes
Weakness: may harm mutual interest
We do not consider the patient's view and we are not valuing their lives
Can have backlash from media and families
Utilitarianism:
Judges as moral or immoral by the outcome, consequences
We might not tell them as this has a better outcome for our research and potentially our medication can help thousands of patients in the future
Happiness objective function = ∑ (hedons) - ∑ (dolors)
Weakness: may harm individual happiness
We do not consider the patient's view and we are not valuing their lives
Can have backlash from media and families
Duty Ethics:
Moral judgement based on sets of rules, not consequences.
We shouldn't tell the patients as this goes against the standard methodology of clinical trials
We do not consider the patient's view and we are not valuing their lives
Can have backlash from media and families for company but also the scientific framework and philosophy
Rights Ethics:
Rights of all parties to the decision, about process not consequences
We should tell the patients as they have a right to know about it
But we also have a right to not tell them
Weakness: challenging to make final decisions
We might skew the data if the patients know they have the placebo as we don't know if the benefits of the medication is due to the placebo effect or the medication
If this is a successful trial and going forwards gets approved, this might endanger people
Virtue Ethics:
About the morality, character of the decision maker, not about consequences.
We might tell the patients as they should know and if we have a sense of integrity, we know that we'd like to know if we were in their situation
issues
We might skew the data if the patients know they have the placebo as we don't know if the benefits of the medication is due to the placebo effect or the medication
If this is a successful trial and going forwards gets approved, this might endanger people
If we are just acting out of virtue then we might skew the data as we are not acting objectively but subjectively
Device Regulation
DHF&DMR
DHF Design History File: Full description of the Design process including all key documents and project management records
DMR Device Master Record: Collection of documents specifying a device and the processes required for its manufacture
Verification:
Laboratory testing to verify that the finished device meets input requirements
regulation
the only regulation that applies to medical device developers BEFORE you file for 510(k):
21CFR 820.30 – Design Controls
Validation
Clinical Evaluation to show the device performs as intended in the hands of the user
What is a Medical Device?
Medical device means any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article
intended to be used for diagnosis or treatment of a disease or disability…
...plus disinfectants of other devices.
(A thing... which is not a drug)
Technical File
what is it?
Collection of technical documents
what is it for?
Evidence that the device complies with regulations
Ethics and Socially Responsible Engineering
ethic
personal ethics
professional ethics
Morals
Definition: Personal rules that govern how we behave towards others
Purposes of Codes
“Framework” , “spirit of the code”
Micro & Macro distinction
micro
Whistleblowing
Corporate Responsibilities and Loyalties
Beware of Groupthink
Falsifying Records
Respecting Intellectual Property
macro
Environmental responsibility
Techno responsibility
Customer/stakeholder/social responsibility
values
Influenced by upbringing, family, schooling, culture, religion
Engineers Australia Code of ethics
TO DEMONSTRATE INTEGRITY
TO PRACTICE COMPETENTLY
(sometimes turn work down to remain professional)
TO EXERCISE LEADERSHIP
TO PROMOTE SUSTAINABILITY
Regulatory Affairs & Medical devices
Sleep
What is sleep?
sleep is
Naturally-occurring state
Periodic and recurring
Involved both mind and body
Involves the temporary suspension of consciousness
Involves the relaxation and inactivity of muscles - semi-paralyzed state(if not happen, could be disorder)
Involves reduced responsiveness to external stimuli
sleep is not
Not coma
Not anaesthesia(still have half sense, like feel ur hand burns)
Not passive
Functions of sleep?
Sleep-wake cycle:
Circadian rhythm( process C)
Sleep- wake homeostasis(process S)
Common sleep disorders and their burden and impact
Sleep Related Breathing Disorders
Obstructive sleep apnoea (OSA)
Insomnia
Sleep as a health risk factor
if not sleep for 6-9hrs
premature mortality,
Cardiovascular disease
Metabolic dysfunction and obesity
Cognitive decline and dementia
Challenges for sleep disorder analysis and treatment monitoring
Therapy monitoring
Do patients use therapy? How much per night?
Is dosage correct?
Treatment requirements may change over time
Can we detect exacerbation of certain comorbidities eg CHF, COPD?
opportunities
Physiological signal capture: low cost data correction
Longitudinal data capture: smart phones, internet...
Data analytics: modern machine learning methods(deep learning)..
diagonosis
Current best practice test is expensive and inconvenient
Home sleep testing is more convenient
Daytime test is better
Multi-night monitoring is better
Innovation on tech:
DePuy - ASR Hip
What was the device for?
The “ASR” stands for articular surface replacements, meant to replace a damaged or diseased hip.
What was found to be wrong with it? (i.e. Why was it recalled?)
Both ASR systems have an unusually high early failure rate — studies have shown 21% of the hip implants have to be replaced within 4 years after implantation, and half have to be replaced within 6 years, compared to 12% to 15% at 5 years for other devices — and both involve dangerous metal-on-metal bearings that can degrade under normal wear-and-tear, releasing metal shavings and flakes into the bloodstream, as well as toxic chemicals like cobalt and chromium.
Who recalled it and was it compulsory?
DePuy recalled the implants from the market in 2010(even thou according to legal documents, DePuy knew its hip implants were defective before the recall. The company continued to sell its remaining devices before issuing the recall.), Australian health officials recalled the ASR products from their market in 2009 after intervention by the TGA.
How did it initially get approved?
The DePuy ASR hip implant was approved through the FDA's 510(k) program, which allows a medical device to enter the market without extensive preclinical testing. ... When metal-on-metal hip implants were first released into the market, they were thought to be overtly superior to plastic or ceramic models
Did the company cut corners?
DePuy failed to manufacture the ASR device to its correct specifications follows on from other findings made by Mr Langton and other researchers, which suggest that the overall design of the ASR XL – the total hip replacement version of the device – led to more metal debris being shed in patients, than from comparable metal-on-metal devices. 30 percent of the ASR resurfacing devices had failed, they were too small.
According to legal documents, DePuy knew its hip implants were defective before the recall. The company continued to sell its remaining devices before issuing the recall.
Were there loopholes in the regulations? (Do these still exist?)
Yes. FDA's 510(k) program-- allows a medical device to enter the market without extensive preclinical testing. They still exist, though divided into 2 programs: The special 510k, and the abbreviated 510k.
Were there loopholes in the regulations? (Do these still exist?)
Yes. FDA's 510(k) program-- allows a medical device to enter the market without extensive preclinical testing. They still exist, though divided into 2 programs: The special 510k, and the abbreviated 510k.
Were mistakes made / were things reported incorrectly?
Neither of the DePuy ASR hip implant systems were properly tested
What were the ramifications? (legal battles/company reputation/does the company still exist?)
On 29 June 2016, the Federal Court approved the settlement of the DePuy ASR Hip Implant Class Action for $250 million plus interest and including legal costs, without admission of liability by DePuy or Johnson & Johnson. DePuy has already offered to pay for all costs related to revisionary surgeries required for those who have received a defective ASR hip implant. Johnson & Johnson announced in a January 2013 press release that it had set aside close to $1 billion in addition to the $3 billion set aside in 2011 to compensate those who received a defective metal-on-metal hip implant from the company.
And the company still exists.
Bioelectronics
• Basic circuit principles
• Total current = ∑𝑛𝑛 𝑖𝑖𝑛𝑛
• What is Bioelectronics?
• Solving simple Bioelectronics problems
Pacemaker
Finger Pulse Oximeter
