ECE BME QUIZ 1

Point of Care Sensors (PoC)

Must be able to perfrorm diagnostics away from centralized testing labs like:

- Hospital Bedside

small phys offices

pharmacies

home

- automated, disposable, hand-held

Diagnostics for HIV/AIDS

- 39 M people living with HIV worldwide

- 1.4 M deaths annually

- ARV drugs available

- 1/8 are able to be tested for HIV/ AIDs

- testing not widely available in 70% of countries with epidemic

Personalized/ Precision Medicine

A model to make medical decisions for patients based on their individual response to disease and subsequently administered drugs

- for cancer

- for infectious disease

Immuno- Engineering

- PoC sensors for continuouse patient testing

- Monitoring patuent immune systems

- Engineering immue system

Personalized Predictive Systems

- Bioelectronics' sensor data

- patient EMR data integration

- predictive theranostics system development

Biosensors

Detecting devices that can detect specific substances in cells

Biochips

microelectronic-inspired devices that are used for delivery, processing, analysis, or detection of biological molecules and species

Biochips and Biosensors

- used to detect cells, microorganisms, viruses, proteins, DNA and related nucleic acids, and small molecules of biochemical importance and interest.

Overview of Biosensor System

Sample -> Biological Elements -> Transducer (can be electrochemical, optical, colorimeteric, mass, magnetic) -> Signal Processing (signal amplification)

Biomarker

a biological molecule found in blood, body fluids, or tissues that is a sign of a normal or abnormal process or of a condition or disease.

may be used to see how well the body responds to a treatment for a disease or condition

also known as molecular marker and signature molecule

Application of Cell Biomarkers

Differnt types of blood cells (immunology)

protiens expressed on cell surface

- CD4/CD8 -> Biomarkers for HIV/AIDS management

- CD64 and CD11b -> bacterial infections like sepsis

DIfferent fucntions/ Properties of cells

- cell motility

-chemotaxis: attracting cells towards chemical graditent in their enviornment

Cell stiffness

Phagocytic ability

- to engulf and destroy large foreign particles, microbes , and dead celll debris larger than 0.5 um

CBC (Complete blood cell count)

RBCs

Platelets

Basophilis

Eosinophils

Monocytes

Lmphocyctes

Neutrophils

Neutrophilis Testing Determines:

- bacterial infection

chemotherapy

inflammation

chronic leukemia

aplastic anemia

Lymphocytes Testing Determines:

bacterial infection

hepatitis

hiv

leukemia

lymphoma

Monocytes Testing Determines:

Viral Infection

Bacterial Infection

Leukemia

Chronic Inflammatory Disease

Eosinophilis

algeric reaction

skin inflamation

parasitic infection

inflammatory disorders

Basophils

serious food allergy

inflammation

leukemia

Platelets

Blood Clotting

Viral Infections

Cancer

RBCs (Red Blood Cells)

Anemia

Polycythemia

Blood abnormalities

Proteins Bind to

Ions

Sugars

Fats

Nucleic Acids

Roles of Proteins

Catalyze Chemical Reactions

Provide Structure to Cells

Control flow of material through cell membrane

Control gene function

Protein Binding

their chemcial surfaces at respective binding sites of one protein must be complementary to the second

Antibodies

produces in response to an infection or exposure to foreign substances

Y shape

Fab = Antigen binding part

Fc = Constant Part

They recognize specific locations of specific proteins and bind to them

Antigen (Ag)

Proteins expressed on blood cell's surface, may be circulating proteins in blood, or proteins expressed on microbes

Epitope (Binding site): is a location on a protein to be recognized by the antibody for binding

Proteins can have more than 1 Epitope

Cluster of Differentiation (CD)

protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells

(e.g) CD4, CD64, CD11b, ect.)

CD for humans is numbered up to 371

Immunophenotyping

a technique used to study the protein expressed by cells

CD and population

Designed using a + or a _ symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule

- CD4+CD8- (expressed CD4 but not CD8)

- Some cell populations can also be defined as hi mid or low indicating an overall variability in CD expression.

DNA (deoxyribonucleic acid)

contains the genetic information used for

- growth

- development

- functioning

- immunity

- reproduction

Conposed of two chains coiled around to forma doble helix strucutre

Base Pairs in DNA

A-T : 2 H bonds

C-G: 3 H bonds

DNA denaturing

Double strand of DNA unwinds to single strands

happens if you increase the temp. or pH and breaks the H bonds between base pairs

resulting strands are exact complements of each other

RNA

single-stranded nucleic acid essential in various biological roles in particular, regulation and expression of genes

DNA Amplification

A single copy of DNA is expoentially amplified to generate millions of more copies of that DNA segment

Primers

short segments of DNA that guide DNA polymerase to the section of DNA to copy

DNA polymerase

Enzyme involved in DNA replication that joins individual nucleotides to produce a DNA molecule

CRISPR/ Cas9 - DNA editing

cells dna can be cut at a desired location, allowing existing genes to be removed and or new ones added

Molding and Prototyping

create an inverse of the original model and develop a mold

pour material / liquid on the mold

let it harden

Photolithography

steps:

Clean wafer

Spin-coat resist

- dependant on thickness, speed, time

Soft Bake:

- promotes adhesion

- what temperature and how long

Expose Photo resist (PR)

- what contact method

- what exposure/wavelength/dosage/energy and time

Post-exposure bake

- helps halting chemical reactions started by exposure

- what temperature and how long

Develop the wafer

Inspect wafer

post bake

- removes any leftover solvent and promotes adhesion

Cleanrooms

need yellow light to prevent unwanted exposure of photoresist to light of shorter wavelength

desinged to haev low levels of

- dust

airbone organisms

- vaporized particles

cleanliness level quantified by number of particles per cubic foot of air

Photolithography Pattern transfer

- radiation

-mask

-photosensitive material

-substrate

-photosensitive materials properties change only where exposed to radiation

-spray substrate with developer solution

1) Positive resist developer solution removes exposed material

2) negative resist developer solution removed unexposed material

wafer cleaning

level of cleaning dependent on:

- contaminants/ dust particles and feature sizes

contaminates include

- solvent stains (acetone)

- residue if reusing

- dust particles

-vapors

cleaning techniques in order of severity

Super Critical Cleaning

Ultrasonic Cleaners (use 20-400 kHz range)

Mega sonic cleaners (use in the 800-2000 kHz range

Wet Cleaning techniques

Wafer degreasing

- very light cleaning, removes dust or light organics

- chemcial regents: acetone, IPA< DI, IPA, N2 dry

- Standard clean 1 (SC1)

- RCA1

- removes light organics

Chemical Regents: DI water, ammonium hydroxide, and ydrogen peroxide

Standard Clean 2

- removes metal ions

Piranha Cleaning (hazardous)

- chemical regents: Sulfuric acid and hydrogen peroxide

RCA Clean

Removal of organic contaminants (SC1)

Removal of thin oxide later

Removal of ionic contamination (SC-2)

wafer priming

preparing the wafer for a resist coating

good for adhesion

high humidity and exposure of the wafer to water solvents often adversly affects adhesion

controlling humidity and dehydration bake help but additional priming steps include

- adhesion promoter (chemical that helps with adhesion of photoresist to the wafer)

Spin Coating

procedure used to deposit uniform thin films of specified thickness to flat substrates

tool used for spin coating material is applied on the center of the substrate

wafer is then rotated at high speed in order to spread the coaring material by centrifugal force

spin coaters with automatic spin speeds calibration

the higher the angular speed of spinning the thinner the film

thickness of film dependant on viscosity of the PR and concentration of the polymer

Soft Baking

also called prebake

promotes adhesion of photoresist to substrate

hotplates are useing in 60 to 110 C range

too much heat can degrade photosensitivity

Masks in Photolithography

reflect the pos/neg of the microfluidic chip design

masks are made of optically flat glass

mask is coated with an absorber layer

pattern is transferred to the absorber layer

- e beam lithography depending on resolution needed

masks can be contact or proximity

projection printing uses masks farther away from the substrate that generate an image at the substrate surface

Exposure for Photolithography

UV exposure systems

- G line : 435 nm

- H line : 405 nm

I line: 365nm

Deep UV range from 150 to 300 nm

Extreme UV range from 10-14 nm

dose requirments are photoresist dependent

Post Exposure Treatment (resist Dependent)

additional processing needed to halt a chemical reaction or to complete a chemcial reaction that was initiated with UV exposure

POst baking exposure - heat helps complete the reaction : SU_8

other waysL

-vacuum treatment

- treatment with reactive gas

-flood exposure with other forms of radiation

wafer development

developing shows the image transformed into a structural pattern

devloping the resist selectively dissolves parts of the resist

wet development

- solvent or aqueous based

solution either dissolved by variation in molecular weight

Post Processing of Photolithography

residue needs to be removed from the surface and out of any small features

oxygen plasma is used to lightly clean the surface

resist is post bakes

- removes solvents

- increases adhesion to surface

high heat and longer times help adhesion but avoid profile degradation

photoresists

change structure when exposed to radiation

composed of sensitizers and solvents

sensitizers are the photosensitivity of the resist and composed of molecules which affect the solubility of the resist when exposed to radiation

resists can be positive or negative tone!

Positive Photoresist

breakdown of molecular chains occurs within the polymer chain via light exposure

light reacts with the material to break down the polymer

exposed material becomes more soluble while areas that are unexposed retain their shapes

Common materials:

PMMA resist

DNQ resist

Negative Photoresist

negative tone - polymer further crosslinks or changes into an insoluble product due to light exposure

upon irradiation, matieral either increases in molecualr wright or photochemically transformed to form new insoluble products

becomes insoluble in organic (traditional) or aqueous (newer) developers

resolution limited by film thickness

has good adhesion to the surface

common example: SU 8 resist

Metal Lift-off profile

refers to the process of patterning a metal film onto a wafer surface

ease depends on

PR profile (pattern resolution sep between electrodes)

Pr thickness

PR type

Thickness of metal deposited

type of deposition method used (evaporation, sputtering)

Thin Layer metal Deposition

Mask

Pattern PR

Achive liftoff profile

Sputter Metal

Strip PR leaving metal behinf

Silanzing the Master Mold

Silanization is used to prevent the PDMS from adhering to the master mold

Process: a drop of chemical is placed in a vial and placed in a desiccator with the master mold

the desiccator is placed under a vacuum causing the salinizing agent to evaporate and form a monolayer on the surface of the master that will prevent the PDMS from sticking to the master

PDMS (polydimethylsiloxane)

can be used to perfrom rapid prototyping using a master

fast, easy fabrication of microchips

irreversible bonding to other PDMS, glass, and silicon

Soft Lithography

Pattern si wafer with resist (SU-8) to form the master

silanizing the master mold

degassing can be done by centrifuge

cure it at 60-125 C

PDMS Processing

CH3 groups make PDMS durface hydrophobic

o2 plasma is used to make the surface hydrophilic (for bonding to other surfaces and to wet the channel)

For microfluidic application we want to wet the channels

r^2 (coefficient of determination)

A higher \(R^{2}\) means the data points are very close to the regression line, showing a strong relationship.

A lower \(R^{2}\) means the data points are scattered far away from the line, showing a weak relationship or a lot of natural noise.