Bikanta’s (YC S14) Tiny Diamonds Find Cancer Before It Spreads
techcrunch.com
techcrunch.com
> these nanodiamonds can detect molecular abnormalities at a much earlier stage, essentially stopping cancer from spreading any further
> Current methods are unable to detect small tumors or breakaway tumor cells that lead to something called micrometastatic tumors, which can go undetected at the source and lead to the spread of cancer throughout other areas of the body.
From pg's essay Frighteningly Ambitious Startup Ideas[1]:
> It will seem preposterous to future generations that we wait till patients have physical symptoms to be diagnosed with cancer. Cancer will show up on some sort of radar screen immediately.
> (Of course, what shows up on the radar screen may be different from what we think of now as cancer. I wouldn't be surprised if at any given time we have ten or even hundreds of microcancers going at once, none of which normally amount to anything.)
The test in question is CEA, carcinoembryonic antigen, where a standard range is 0.0 to 2.5ng/mL and mine is 8.0. What if I had had this test a year ago?
http://en.wikipedia.org/wiki/False_positive_paradox
(I get the statistics, but personally I would still happily sign up to be tested for everything possible.)
All that said, good luck with your treatment. That's a much tougher diagnosis than mine was.
"The CEA test has a specificity of between 30-80% and it is not recommended by the National Institute for Health and Clinical Excellence (NICE) for the diagnosis of early colorectal cancer" http://www.patient.co.uk/doctor/carcinoembryonic-antigen-cea
Causes of false postive CEA include but are not confined to:
"Inflammatory Bowel Disease.
Pancreatitis.
Liver disease.
Tobacco use can lead to elevated CEA levels. (CEA is elevated in 19% of smokers and only 3% of the non-smoking healthy population.)
Diverticulitis.
Hepatitis.
Peptic ulcers.
Hypothyroidism.
Cirrhosis of the liver.
COPD.
Lung infection.
Pleural effusions.
Biliary obstruction.
Treatment with oral 5-FU.
High serum glutamic-pyruvic transaminase (sGPT) levels.
Non-malignant liver disease, including cirrhosis, chronic active hepatitis.[6]
Chronic kidney disease.
Pancreatic disease.[7]
Inflammatory bowel disease, diverticulitis, irritable bowel syndrome.
Respiratory diseases, eg pleural inflammation, pneumonia.
Smoking.
Ageing.[8]
Atherosclerosis
"http://www.kantrowitz.com/cancerpoints/tumormarkerfalseposit...
Thanks for the share from PG's article. We are definite believers that it is possible to detect cancer significantly before symptoms begin to appear!
So assuming this is intended to be a screening tool, is there any feasibility data regarding fluorescence from even more than a couple centimeters within human tissue? I am skeptical that you will be able to see a lung or colon tumor for example... two of the three most common cancers in America.
I am a physician and consider myself very knowledgeable in imaging (Radiologist) as well as fairly informed about optical imaging (large institution with quantum dot and other types of opitcal research).
Major props for using a cheap source of nanodiamonds. Any issues getting ones that are the right size/shape?
http://mobile.nytimes.com/2014/08/01/business/fda-to-regulat...
My general understanding in health startup world ("real" health startup - not just a new mobile app that measures vitals) is that if you have a truly compelling product that is clinically proven (sounds like this is?) then the venture/acquisition/funding landscape is pretty straight forward and has high returns - something that doesn't generally characterize the path of the AirBnB's, Heroku's, Homejoy's, etc. of the world.
In a long-ago materials startup, we had 30+ Phase I, 6 Phase II and 3 Phase III SBIRs. The money was helpful (VC funding on topic was thin at the time).
Very few of our SBIRs were exactly on point with our product development goals. This created resource allocation tensions around pushing product development vs. performing on the SBIR contracts. Something to consider when thinking about SBIR funding.
Sorry for the basic questions, I no longer have journal access :( and this sounds neat :)
P.S., oh, and do they blink?
The Stokes shift, as you can see is very large. The quantum yield is 1 and they don't blink. We are initially focusing on stabilized nanodiamonds with various chemical groups put on the surface to have them ready for further conjugation. Email us at info@bikanta.com and I can have a further conversation with you if you would like.
Continuing with the human studies thought, are these particles seeing RES uptake? I assume, based on the high QY, that these the emission centers for these particles are protected by a thick shell and/or corona. General handwaving from the FDA was that they were as concerned with particles persisting as with elemental toxicity. Is there a predicted degradation pathway for these particles?
Can these particles be made with a hydrodynamic radius, including corona, <8nm? Is it possible to dope them to get better NIR emission?
Unrelated to technical stuff: I thought that a YC thing was that you had to move to San Diego for a few months. That doesn't seem all that conducive to wet lab work, in fact, it seems like a non-starter. Is that still a requirement for the bio-related startups? If so, how how disruptive is it?
Thanks for the answers!
- How quickly are the diamonds removed from the body?
- What is their size compared to the smallest capillaries i.e. any potential for blockages?
How do you plan to deal with the fact that early cancer screening may be detrimental to health outcomes?
Many a great drug (and visualization agent) has failed because of kidney toxicity.
It's surprising that there are no MDs on the team.
(disclaimer: I run a project in this area)
http://www.nature.com/nbt/journal/v32/n5/abs/nbt.2892.html
There is also an overview editorial in that issue of Nature Biotechnology.
http://www.nature.com/nbt/journal/v32/n5/full/nbt.2897.html
I remember seeing reviews in Lab Chip and Nat Rev Clinical Oncology recently.
http://pubs.rsc.org/en/Content/ArticleLanding/2014/LC/C3LC50...
http://www.nature.com/nrclinonc/journal/v11/n3/full/nrclinon...
The introduction sections of those papers should give you plenty of references to read. It's a good idea to look into the devices/methods used to enrich CTCs from blood prior to screening; Toner's devices based (in part) on EPCAM expression, and the CellScreen device (size/morphology), in particular.
These nanodiamonds range in size from 15-100nm, so the kidneys will not be their primary route of clearance. It is also crucial to note that with any nanoparticle development, coating is a major factor in its biodistribution behavior. Coatings can and have been designed in more recent work regarding nanomedicine that minimize various biodistribution issues.
Coatings won't help this problem unless you can somehow change the shape of the crystal to fit through the slit OR get it to cross into the renal luminal space via transcytosis or excreted more efficiently in the biliary tree. All difficult propositions.
I really hope novel techniques like this work but this particular on seems very problematic. If I were you I would complete a serious set of toxicity studies very early on to make sure this isn't a fish that's dead in the water.
Edits: clarifying the points
http://pubs.acs.org/doi/full/10.1021/ja0567081 http://pubs.acs.org/doi/abs/10.1021/ja4016815 https://www.opticsinfobase.org/boe/abstract.cfm?uri=boe-5-4-...
Question (I know almost nothing about medicine/biology): I can see how nanodiamonds are useful for general imaging, but how will it help differentiate cancer cells from regular cells? Do the nanodiamonds bind to anything or is it just a emission light source? Thanks.
Why is it hard to imagine?
Now, if you have a patient that has been already diagnosed with cancer, and the nanodiamonds are used to monitor tumor progression or watch for metastasis, then that's a different story.
Note: these aren't the same as vaccines, since cancer isn't a communicable disease (largely).
Your love is
like radiant diamonds
bursting inside us...
I get how these can be used to help imaging, but I'm not clear on how exactly they target cancerous cells in particular. Are they attached to antibodies that seek out specific antigen markers of cancerous cells?
Thus, how big does the abnormality have to be before its conclusive using this technology?