Restricted/Do Not Distribute/JT

Molecular Diagnostics: Bio 2064

Medical Devices and Applications

Introduction
• Development of medical devices based on science and engineering, including
physiology, cell, molecular biology, biochemistry, nanotechnology,
electrical and electronic engineering
• To address issues associated with a disease, clear understanding of the
disease, and patho-physiology must be established
• Medical devices for clinical applications include external and
internal implantable devices
• The objectives of the medical devices can be classified based on the following criteria:
a) To Monitor Pathophysiology (i.e monitor conditions associated with the disease)
b) Diagnostics (i.e to collect data or perform test to determine normal
versus abnormal condition)
c) To treat the underlying condition associated with the disease
 Restricted/Do Not Distribute/JT

Medical Devices and Applications

Focus of Medical Devices: examples

• Cardiovascular disease
• Cancer
• Infectious Disease
 General Definition
Medical Biotechnology: fusion of
biology, medical science, and
technology to generate products for
medical applications
 Main Components of Medical Biotechnology
Biology/Medical Science:

• Understand cell-cell and molecule-cell interactions

and communications

• Understand biochemistry of molecules: sequence, structure, and function

relationships as well as its regulations

• Understand human physiology/human diseases

Biotechnology/Technology

• Genetic Engineering, biochemical, bio-engineering, optical,

delivery technologies, and etc
From Science/medical Science>Technology>Products

Knowledge

Medical Biotechnology
Products /Technology
 Understanding Science: Skin Color

Cell To Cell Communication: Modulation of Human skin Color

FZP I
FZP VI
Its Hot! I Need Sunscreen!
More Prone to Less Prone
Skin Cancer to skin cancer

Fitzpatrick Scale Cell To Cell Communication Human Skin Structure

(skin color) : I-VI

Genetics of skin type

References:
J. Investigative Dermatology, 2012, 132, 1222-1229
skinipedia.org/skin-essentials/melanocytes
Bio-Essays 1998, 20, 712-721
 Understanding Medical Science: Melanoma (Skin Cancer)
Human Skin Color and Melanoma

1. Change human skin colors with bio-actives (chemical, bio-resources, natural, and etc)
Products In the market: SK-II, Neutrogena, Shiseido, and etc
2. Identify skin cancer (incl. melanoma) with medical technologies
3. Statistics: 1 in 5 Americans will develop skin cancer in their life time,
and in 2009, 61 646 Americans were diagnosed with melanoma (US-CDC, WHO)

Refs: Learnaboutcancer.net Size and shape Benign Vs

Mayo Foundation for Medical Education and Research of melanoma Malignant
 Products: Advanced Medical Diagnostic
Tools To Detect Melanoma
FDA approved and clinically proven
multi-spectral camera for
under the skin imaging to detect early
stage melanoma with 95% sensitivity)
(Source: MelaSciences)
MM=Melanoma (Cancer)
PN: Pigmented Nevi
SK: Seborrheic keratosis
NOR: Normal
BCC: Basal Cell Carcinoma (Cancer)
Based on Raman Spectroscopy, Raman Spectra:
the device can differentiate normal Diagnosis of Melanoma
melanocyte from melanoma (ref: J. I. Investigative Dermatology,
(Source: Verisante Technology) 2004, 122:443-449)
Innovations in Medical Device and Diagnostic
System: Increase survival rate of cancer patients
• Microfluidic chip to collect circulating tumor cells (CTC)
• Quantity of CTC can be used to determine survival rate and effectiveness of
chemo-drugs

Microfluidic Chip

Cell Search CTC system

Refs: MIT Technology Review

Medical Diagnostics System: Helps doctors to
predict treatment outcome
Breast Cancer Patients :Survival Rate Modify or change anti-cancer treatment
Based on CTC counts options based on CTC count
 Restricted/Do Not Distribute/JT

Isolation and detection of CTC

Microfluidic System

http://www.medgadget.com/2013/04/mgh-ctc-ichip-sets-new-bar-for-circulating-tumor-cell-
detection.html
 Restricted/Do Not Distribute/JT

Isolation of CTC through Microfluidic system

Detection of Circulating Tumour Cells (CTC)

•Microfluidic Technology is used to analyze

CTC from blood
• CTC are detected when the cells attached to
graphene oxide nanosheet coated on surface
containing gold particles
• Demonstrated to be able to detected few
CTC (3-5) out of 5-10 billion blood cells
http://www.medgadget.com/2013/10/new-graphene-oxide-based-microfluidic-chip-captures-circulating-
tumor-cells-with-high-sensitivity.html
 Restricted/Do Not Distribute/JT

Nanowires and Nanocantilevers

• Nanowire: Binding of molecules to nanowire sensor causes change in conductance of the

nanowire which can be quantitatively analyzed in a microfluidic system
• Nanocantilevers: Binding of biomolecules to capture surface coated with antibody changes the
physical structure of nanocantilevers or change in resonant frequency which be
detected and quantitated
http://www.nature.com/nrc/journal/v5/n3/fig_tab/nrc1566_F3.html
 Restricted/Do Not Distribute/JT

Components of Biosensors

http://upload.wikimedia.org/wikipedia/commons/e/ec/Biosensor_System.jpg
 Restricted/Do Not Distribute/JT

Glucose BioSensor: Glucose Oxidase

• External Medical Device that measures glucose level in Blood

•Based on enzymatic reaction carries out by Glucose Oxidase
in the presence of glucose
• Hydrogen Peroxide is measured by electrode
(electrochemical probe) that can measure change
in hydrogen peroxide level or dissolved oxygen

http://flylib.com/books/en/3.110.1.66/1/
 Restricted/Do Not Distribute/JT

Medical Devices and Applications

•Objective: To measure glucose in saliva

• Structure: Carbon Nanotube coated with
pyrene-1-boronic acid that binds glucose
•Binding of glucose changes physical structure
of nanotube, which can be detected by sensor
•Currently in development phase for future
application

http://www.technologyreview.com/view/514456/carbon-nanotube-sensor-detects-
glucose-in-saliva/
 Restricted/Do Not Distribute/JT

Implantable Glucose Sensor

•Measure Glucose in Interstitial Fluid for up to 6 months

•Encased in Glucose sensing polymer which
can be excited by light to indicate change in glucose level
• Output light is transmitted to record the signal

http://senseonics.com/product/the-sensor
 Restricted/Do Not Distribute/JT

Molecular Diagnostics System

• Automated system to extract and purify DNA from patient samples

(plasma, serum, and cultured tubes)
• Extracted DNA would be PCR amplified and analyzed to detect pathogens, including
Cytomegalovirus (CMV)
• Other applications (pending approval) includes detection of
HIV, HCV, and HBV and HPV.
http://www.medgadget.com/diagnostics/page/2
 Restricted/Do Not Distribute/JT

Micro-needle Device

• For TB testing using Tuberculin

• For delivery of drugs

Microneedle For drug Delivery

https://dolcera.com/wiki/images/thumb/Microneedle.jpg/300px-Microneedle.jpg
 Restricted/Do Not Distribute/JT

Summary
• Development of medical devices are based on understanding of biology, physiology
medical sciences with the use of technologies
• Application of medical devices includes monitoring, treatment, and diagnostics
• Current development of medical devices rely on new technologies,
including microfluidic system, carbon-nanotube, nanowires, and nanocantilevers
• Medical devices for molecular diagnostics include biosensor technology for
external or implantable applications
• Biosensor has incorporated microfluidic system to enhance performance
for molecular diagnostics
• Specific diagnostics systems have been developed to detect glucose level,
using innovative technologies such as carbon nanotubes, and implantable glucose sensor
• For detection of circulating tumor cells (CTC), microfluidic systems have been
developed to separate RBC, white blood cells, and to attract CTCs for quantitation
• Molecular diagnostics System have been developed through automation technology
to allow detection of pathogens (DNA assay) or biomolecules for clinical applications
 Restricted/Do Not Distribute/JT

AUTOMATED MOLECULAR DIAGNOSTIC SYSTEM

http://www.youtube.com/watch?
v=kPnNhHH8d6o