It is 1st part of 2part seminar of 2nd semester in nanotechnology course. It has short intro of inspiration from theranos story, structure of blood, traditional blood test procedure, blood sugar testing principles.
Note- This is just concise part I made for seminar, any scientific inaccuracies is probable and highly regretted. Any constructive criticism is welcome.
3. The Theranos Saga(Motivation)
“Pinpricking” to 250+ tests.
“A drop” of blood-300 Tests
“Few drops” of blood
Theranos Edison
A single desktop minilab for all tests.
Conventional methods:
More time, more blood, expensive, more pain.
Theranos Edison(conceptual)
Ref. NYT
Elizabeth Holmes(famous 1drop picture
SteveJobsesque)
Ref.WSJ
5. Traditional blood test Procedure
Vein Puncture
Tourniquet
Butterfly needle
Bruising
Clotting time
Recovery time
Recurring pain
Artery puncture
One test : ~5-10mL
Traditional blood collection
Ref.-British Heart Foundation
Ref-Very Well Health
8. References
Editorial staff,Blog Post: Integrity line: Elizabeth Holmes: Theranos,
November 2022
Dr.Hayley Wallacy, Blog Post: Patient.info, Blood tests, February
2023
Cancer.net, Editorial Board, February 2022
J. Michael McMillin,Ch141-Clinical Methods: The History, Physical,
and Laboratory Examinations. 3rd edition
Theranos founder Elizabeth Holmes, in her 1st year of Stanford in 2003, devised an idea of patches for taking microscopic blood samples to find out about markers of infectious diseases and propose treatment plans, she applied for patent, and within few months or so she upgraded her idea into a business model: with 300 tests in 1drop of blood. She got funding in millions because of the lucrative 1drop-300 test. However, the one drop model oscillated between one drop and few drops as well as 300 tests to 200 tests in her initial proposal, company’s contracts and advertisements.
Nevertheless, this was a game changer as it was cheaper requires less blood and less time. It was a boon for cancer patients where frequent blood tests drained energy, money and hope of already critically ill patients.
The another highlight of her proposal was a desktop minilab named “Edison” which will perform all of the blood tests in few drops of blood. This technology didn’t existed before. The design, working and internals were classified, some techs were applied for patent. But in all, it was non-transparent.
However, this proposal was marred by inaccuracies, fake results, taking more than a “few drops” of blood and running tests on 3rd party devices.
Since her proposal, this tech was disapproved by subject matter and industry experts because of scientific improbabilities.
Since , this is a combine field of biology, chemistry, physics, mathematics and of course engineering. Before categorically denying or accepting it or being sceptical about its future probability we will look into basic sciences involved in blood testing, in this presentation.
The human blood is made of blood cells and plasma.
Blood cells These make up about 40% of the blood's volume. Blood cells are made in the bone marrow by blood 'stem' cells.
RBCs:Red in colour because of haemoglobin, carries oxygen. 1 drop of blood consists of 5million red blood cells.
In order to constantly make blood cells, haemoglobin and the constituents of plasma, you need a healthy bone marrow and nutrients from food including iron and certain vitamins.
There are different types of white blood cells which are called neutrophils (polymorphs), lymphocytes, eosinophils, monocytes and basophils. They are part of the immune system. Their main role is to defend the body against infection.
Neutrophils engulf germs (bacteria) and destroy them with special chemicals.
Eosinophils and monocytes also work by swallowing up foreign particles in the body.
Basophils help to intensify inflammation.
Platelets help in coagulation.
When blood is taken into an upright tube the cells and certain plasma proteins clump together to form a clot and settle down. The remaining clear fluid is called serum.
Plasma: mainly consist of water which about 90% .
In addition , it contains salts, glucose : can provide free ions and electrons
fats,enzymes: made by lipids proteins- fundamental block: amino acids.
When we lose blood, the loss of RBCs is to made up by hemoglobin which requires draining of iron resources of body. Loss of plasma is to be made up by hydration, i.e water addition to body.
The traditional blood test procedure requires draining of blood by puncturing the vein.
To apply pressure, a pressure band called tourniquet is fatened on hand.
For frequent draining of blood a butterfly needly is inserted into the patient hand and left there.
Now, this is very inconvenient and painful procedure. Especially for critically ill patients where frequent punctures, and incurrent illness delays the recovery time, so the pain is also more. Also in case of artery punctures which is requirement for oxygen level checking in severely ill patients is too painful. Also needle can bend, now just imagine this scenario for a patient who is already weakened by diseases such as cancer, coronary artery disease, etc.
Now, the scientific requirement of blood for testing purposes varies from 2 to 20 mL. The most common blood test CBC requires 5ml of blood, but the pathology technicians generally take 1..5x to 2.5x blood for failsafe cases.
For critically ill, such as cancer patients undergoing chemotherapy requires frequent draining of blood. Let us say 3times a week, now think a cancer patient whose bone marrow is already at too much load(because of cancer spreading to bone marrow) , and is drained about 15times a month. This will translate to about 300mL of blood drain.
A unit of blood which is 450ml requires 12-16 weeks to fully replenish for a healthy person. That will be much slow for sick person. How will they recover from so much blood drain? And hence was Theranos rise to centrestage in blood testing industry.
Haemoglobin the most important part of blood contains iron ions. As you can see from structure that there is additional existence of conjugated pi bonds in the Haemoglobin molecule.
Conjugate pi bonds are the alternate double bonds in a molecular structure.
Conjugated pi bonds lead to delocalised electrons which can relatively easily change their positions. This leads to improved conductivity and transfer of electrical signals.
Amino acids: which contain a carbonyl and amino group, interchange hydrogen to form Zwitter ion structure. Since they are building block of proteins, DNA, fats, this shows that there mere existence with other conjugate molecules can be used for signal transfer.
Hence we can infer how basic biology will combine with electronics and hence fingerprick testing.
The most common fingerprick testing is blood glucose level testing, done by devices known as glucometers.
It started with lab tests of urine in 1950s then evolved into blood glucose testing and then using electronic devices.
Glucose has a cyclic structure, is a monosaccharide carbohydrate, repeating fundamental structure of what we broadly call sugars, which change its structure by transfer of electrons in adjacent aldehyde(-CHO) and alcohol(-OH) to form other enantiomers of itself.
Enantiomers are non superimposing mirror images of a molecule.
Basic science involves three methods reduction, condensation and enzymatic.
Reduction Methods:
Reducing methods are the oldest and take advantage of the reducing properties of glucose to change the state of a metal ion while glucose is being oxidized. Reducing methods are nonspecific, and any strong reducing agent can cross react to yield spuriously elevated values
Condensation Methods:
The aldehyde group of glucose can undergo condensation with aromatic compounds to yield a colored product. In the most commonly used condensation reaction, o-toluidine reacts with glucose to form a glucosamine that has an intense green color. The color is then measured spectrophotometrically to estimate the glucose concentration.
Enzymatic Methods:
The enzyme glucose oxidase reacts with glucose, water, and oxygen to form gluconic acid and hydrogen peroxide. The hydrogen peroxide can then be used to oxidize a chromogen or the consumption of oxygen measured to estimate the amount of glucose present. Glucose oxidase is specific for β-d-glucose, so cross reaction with other sugars is not a problem
Basic science of Glucometer:
Electrons are transferred from the glucose in blood through molecules until it reaches the electrodes in the glucometer. These moving electrons create an electrical current proportional to the amount of glucose in the blood, and the number appears on the monitor.