Minimal volume with minimal information

Minimal volume with minimal information

The WIRED interview with Elizabeth Holmes, founder and CEO of Theranos, has been making the rounds. In Di Cleverly’s post

https://plus.google.com/+DiCleverly/posts/XTn2SDnE9LB

I mentioned that in addition to the minimal amount of blood used, there is a minimal amount of details. Searching elsewhere, even the Theranos website, there aren’t many details. In Di Cleverly’s post, the only decent info was from patents. If you’ve ever read a patent, then you know that it’s often difficult to sort out what’s really going on. So, with Di Cleverly’s help, we have a better picture of what’s going on. A lot of this post are my guesses about some of the details, partly because I’m busy, partly because I’m lazy, and partly because there isn’t a lot out there without really digging. Did I mention I’m lazy, I mean busy?

☼ What was mentioned: small volume and centralized facility

For those that haven’t seen the WIRED or Medscape articles, Elizabeth Holmes dropped out of college at Stanford at the age of 19 and eventually started Theranos with her college funds. The interview talks about how the small volume of blood, from a pin prick, can make the experience, and therefore patient compliance, better. Ms. Holmes talks about reduced and transparent pricing. Essentially none of the technology is discussed. A centralized facility is mentioned. So is that an essential part, i.e., how much can be done off site (e.g. at Walgreens)? Before any young readers decide to drop out like Ms. Holmes or Bill Gates, I think Dave Thomas, founder of Wendy’s makes a good example.

Thomas, realizing that his success as a high school dropout might convince other teenagers to quit school (something he later claimed was a mistake), became a student at Coconut Creek High School. He earned a GED in 1993.)

http://en.wikipedia.org/wiki/Dave_Thomas_(businessman

☼ Detective Work: ESR and microfluidics

On Di Cleverly’s post some detective work was done and a few things came to light, mostly via the patents. The small “nanotainer” is used in a novel centrifuge to get information about the blood sample. Red blood cells (RBC) are called erythrocytes and are just one component of blood. If you put whole blood in a glass tube, eventually the RBCs will sink to the bottom and the plasma will stay at the top. You can speed up this process by using a centrifuge (a device that spins the tubes at many times the force of gravity). The rate that the RBCs go to the bottom is called the erythrocyte sedimentation rate or ESR. ESR alone can tell you something about your health.

An increased ESR rate may be due to:

Anemia

Cancers such as lymphoma or multiple myeloma

Kidney disease

Pregnancy

Thyroid disease

Common autoimmune disorders include:

Lupus

Rheumatoid arthritis in adults or children

Very high ESR levels occur with less common autoimmune disorders, including:

Allergic vasculitis

Giant cell arteritis

Hyperfibrinogenemia (increased fibrinogen levels in the blood)

Macroglobulinemia – primary

Necrotizing vasculitis

Polymyalgia rheumatica

An increased ESR rate may be due to some infections, including:

Body-wide (systemic) infection

Bone infections

Infection of the heart or heart valves

Rheumatic fever

Severe skin infections, such as erysipelas

Tuberculosis

Lower-than-normal levels occur with:

Congestive heart failure

Hyperviscosity

Hypofibrinogenemia (decreased fibrinogen levels)

Low plasma protein (due to liver or kidney disease)

Polycythemia

Sickle cell anemia

Source: http://goo.gl/zKstuW 

The patent mentions a novel centrifuge device with either video or still images of the sample. There are two greyscale figures from the patent in the album below. With image analysis the ESR can be measured without human intervention which minimizes errors.

☼ Microfluidics

Another patent talks about microfluidic devices. I’m assuming those are lab-on-a-chip (LOC) devices. LOCs use microelectromechanical systems (MEMS) to do analysis on very small volumes of fluid. Here’s an example from Harvard that captures trace amounts of tumor cells.

http://goo.gl/jPGZlr

Although genechips or DNA microarray’s aren’t LOCs, it is possible they are being used by Theranos. An image of an Affymetrix Genechip is included in the album below. http://goo.gl/GpMyjx Note the small Eppendorf tubes in the foreground. Those are larger than the Theranos “nanotainer” but they do make Eppendorf tubes the same size as the “nanotainer”. Both the “nanotainer” and Eppendorf tubes have conical bottoms to facilitate removal of all of the liquid. The genechips have target DNA probes attached to the device. If a target gene is expressed, it will bind with the probe on the chip. The readout is typically some type of light whether chemiluminescence, fluorescence, or some combination. The amount of information from these genechips has caused an explosion in bioinformatics and computer processing dedicated to speeding up the analysis of these microarrays.

http://en.wikipedia.org/wiki/DNA_microarray

Because the samples are going to a centralized facility, it’s possible that real-time polymerase chain reaction (RT-PCR) is also being used. RT-PCR is a technique that is used to amplify DNA samples.

☼ Therapeutics and Diagnostics =  Theranostics

I didn’t find any information to suggest that the name Theranos has anything to do with the term theranostics, i.e, therapeutics and diagnostics.

Pharmacogenomics aims to identify the genetic basis of variability in drug efficacy and safety, and ultimately develop diagnostics that can individualize pharmacotherapy. Theragnostics, a term denoting the fusion of therapeutics and diagnostics, is receiving increasing attention as pharmacogenomics moves to applications at point of patient care.

Shifting emphasis from pharmacogenomics to theragnostics

http://goo.gl/6nrkmp

Rapid molecular theranostics in infectious diseases.

Picard FJ1, Bergeron MG.

Drug Discov Today. 2002 Nov 1;7(21):1092-101.

http://www.ncbi.nlm.nih.gov/pubmed/12546841

An example of theranostics from my boss and colleagues is a platform that combines doxorubicin (cancer therapy), herceptin (targeting for diagnosis), and DOTA-Gd(III) (for MRI detection, i.e, diagnosis). So the herceptin targets the product to cancer cells. Gadolinium, chelated to the construct (DOTA-Gd(III)) allows you to see it with MRI (enhances the contrast from background tissue) and the doxorubicin provides therapy at the target (tumor).

pH-Responsive Theranostic Polymer-Caged Nanobins: Enhanced Cytotoxicity and T1 MRI Contrast by Her2 Targeting

http://goo.gl/4PHkLo

So that’s what I could sort out with the help of Di Cleverly’s post and my own digging through a couple patents. If you have ideas or comments, feel free to ask.

#ScienceSunday