Cancer diagnosis? There's an app for that...

Okay, well, not exactly. But pretty freaking close. A "just accepted" article in the journal Analytical Chemistry from Aydogan Ozcan's group at UCLA describes a cellphone-based device for detecting and counting fluorescence-labeled cells (or other fluorescing particles) flowing past the cellphone camera.

This device fantastically uses LEDs pointing in at each other from each end of a cheap microfluidic chamber (i.e. a silicone-coated glass chip) that acts as both the channel for the cells to flow through and an optical waveguide (making the light waves from the LED oscillate and bounce around, kind of like how a fiberoptic works) that enables fluorescence excitation and emission, which gets sent through some cheap lenses and an optical filter (to isolate the fluorescence signal) and picked up by the cellphone's integrated camera.

To demonstrate that this could give useful biological information, they combined the device and phone with an external pump to flow liquid containing particles (either a suspension of fluorescent particles or diluted blood) past the camera. In the version where they analyzed blood, the blood had been dyed with a fluorescent stain that made the white blood cells glow in the LED setup (because the dye stains DNA, and red blood cells don't contain any DNA). Then they wrote some software that post-processed the movie images and counted the particles or cells.They were able to get pretty good detection and resolution of particles as small as 1 micrometer in diameter--which is smaller than most human cells (meaning that even smaller things, like bacteria, might be able to be detected and distinguished from each other).

Could this really be used to diagnose cancer? Sort of. White blood cell counts are a key metric by which leukemia and lymphoma (cancers of the blood) are diagnosed and monitored. This device was able to get white blood cell counts that were really close to those obtained with a fancy blood cell counter instrument. Of course, to do anything more than just count the number of easily stainable white blood cells, people with a lot of biomedical expertise will have to think of ways to apply this detector. For example, from the proof-of-concept experiments they showed, you wouldn't be able to tell what kind of blood cancer someone had, and you wouldn't even get very much information about the status of their blood cancer if they had started on a treatment. Even so, being able to do this accurately with something that costs $50 is revolutionary: most fluorescence-based detectors cost tens of thousands of dollars and require sensitive, fancy optics to work properly. Even the "cheap" versions are a few thousand dollars. This is some LEDS stuck onto a glass chunk with some plastic bits attached. And it works.

Why is this so amazing? Well, apart from that it is small and readable by an extremely common and widely available camera, it is also made of all low-cost parts, so it will be extremely accessible yet gives pretty sophisticated information (fluorescence image readings). Its applications are only limited to what kinds of dyes are available to specifically stain different things you might want to look for in cells or particles, and the ingenuity of the applier in figuring out what to stain with fluorescence and try to look for. There are fluorescence-type stains that can be applied to cancer cells to figure out more about the type, stage and response to treatment of the disease--and while not trivial to apply with this device, potentially within reasonable optimization reach. They can even use different cheapo plastic optical filters to look for different fluorescence colors (besides just the green fluorescence they show in the paper). Of course, if they want to try to look for more than one color at a time (called 'multiplexed' fluorescence), things might get complicated.That requires more than one LED and more than one optical filter, but, I imagine, isn't impossible.

Beyond just white blood cell counts, I can envision this being used as a readout technique for detecting circulating tumor cells (CTCs)--rare cells that are shed by other kinds of tumors into the blood stream. CTCs usually have different proteins and carbohydrates on their outer surfaces than blood cells do, so it's possible to either stain them with fluorescent dyes that don't stain the blood cells, or catch them using antibody grabbers in microfluidic chambers (very similar to the one used in this device) that latch onto those specific proteins and carbohydrates, but let all the other cells flow by. In that case, you could then just stain the captured cells with the same antibody grabbers (left free floating rather than attached to the chamber, and pre-labeled with a fluorescent dye) or some other generic dye for staining all cells or cell parts (like the nucleus).

It will need to be integrated with some kind of pump to be more universally useful, because not everybody has a syringe pump sitting at the back of a closet that they can just hook up and go. It'll also probably need some integrated sample well that can keep the sample 'agitated' (i.e. shaking) during the flow so the particles don't settle and clump up. However, these should be easy enough to figure out (maybe they can plug into the vibration unit on the phone to do the shaking?). They designed their counting software using a platform that is compatible with Android phones--so even though the phones they used in this study couldn't do any integrated processing, it's a very short jump to adapt this device to an Android phone or iPhone and have... (wait for it...) an app for that. lol. I am fascinated to see how this device gets further developed and used, and I plan to buy one for myself as soon as it's available.

(h/t to C&EN News from the ACS for highlighting this manuscript)

Women's Health: Survive your doctor

Around Scientopia this week, we're doing a critical analysis of the "science" (or lack thereof) in women's magazines, exemplified by a bunch of articles in Women's Health magazine. Most of the articles we're looking at are pretty ridonkulous, and they deserve the takedown they're getting. The one I picked, however, "Patient care: Survive your doctor" actually gives pretty good advice: be your own health advocate.

As they point out in the article, while "it's a doc's job to (manage) your medical problems," we can't rely on them to know what's going on inside our heads and bodies when we aren't talking to them or following up. We tend to fall into the "respehct mah authoritah" trap when doctors are telling us what is (or isn't) wrong with us, but when it comes down to it nobody knows your body better than you do. Just like no single patient is guaranteed to fall in the middle of the symptom distribution, no one physician is guaranteed to notice, synthesize and correctly identify every medical issue. I definitely groaned at the mention of "House" as an example of how important medical history is to diagnosis, but as a point it is relevant. These days, unless you have a legitimate medical home and someone who knows you, you are the only one who knows your story and you have the right to be heard by your physicians.

This touches a personal nerve for me: last year, my close cousin died of adrenocortical carcinoma. I've written about this before. She experienced the classic demographic-based misdiagnosis--skin getting bad? weight gain? hair loss? anxiety? Periods getting weird? You're a young woman, these are common, just hormonal, maybe polycystic ovaries, try to get more exercise, try to rest more, do you want to talk to a counselor? Let's try prozac. In the end, it took about three years or so of this getting worse, and worse, and worse, until she was hardly sleeping, had the classic Cushing's moon face/abdominal distension, and kept pressing on going to the free clinic until the nurses there finally said "Look, we're going to just test your cortisol." It was so sky-high, it practically hit the limits of the test. Part of the problem was that she just kept assuming, "Well, I guess the doctors know what they're talking about. I must just need more exercise. I'll try to eat healthier," as the tumor grew and grew, eventually invading her vena cava and reducing her probability of survival once it was finally found (in Stage IV) by more than 75%.

What could have been done? Later on, not much. By then it was too late. But early on, the if-only's of her situation are just too painful for us all to contemplate. If only we had noticed, if only we had been able to push her to get more opinions, if only she had better (or any) health insurance during that time (and that's a whole other story...). If only we were all better trained to be our own health advocates. Then she might still be here, laughing with us until she almost pees her pants at the Thanksgiving "kids table" and delighting in with my daughter, her namesake, who would have loved her silliness, spirit and flair.

So, I appreciate what this article says: you have to stand up for yourself, and you have to stay informed. Don't just accept everything you're told, find a physician who you connect with and who you can talk to. Don't just see your gynecologist for every problem, find yourself a medical home. Educate yourself on the options available to you, keep up with current opinions and don't always just accept the so-called 'simplest' explanation.

On the other side of this coin, though, is the risk of falling sway to the woo. Woo is just as dangerous as misdiagnosis. Woo is attractive because it says it can explain these things we just don't biologically understand--it's a catch-all for the fear, uncertainty, pain and anxiety that comes with any complex medical issue. Since there is almost no such thing as a truly simple medical issue (besides things like, say, colds and ear infections), it's that much easier to be drawn to the mystical or "holistic" explanation, the same way humans are drawn to any seemingly satisfying magical answer for their problems (whether financial, health or psychological). But just like time shares in Florida, if it sounds to good to be true, it probably is.

Staying informed about the evidence-based information on possibilities, options and outcomes is our best bet to manage our own health care. None of us are too stupid to understand it, and there are lots of resources out there to help the unsure (like our very own PalMD, for example). Be your own health advocate, but use your brain about it, and accept that you'll either fall within the normal range of the distribution or you won't, and it's your job to trust your instincts about seeking help.

Repost: Culture gap: synthetic chemists and learning biology

Apologies for more reposting... I'm still trying to get out from the vacation backlog of life. New thoughts to come soon!

I started responding to this comment:

Now that you have invested so long to transform in to a ‘chemicalbiologist’, would you mind suggesting some quick tips from your journey for the people ho want to take the same path? Are there any books or some crash courses etc?

And got so in depth that I decided to make it a post of its own. So here are my thoughts about where to start to develop better flexibility as a synthetic chemist who wants to work on bilogical problems.

The best crash course I got was weekly lab meetings in a lively, rigorous yeast genetics/molecular biology/kinase signaling lab (one of my postdoc labs). I started out so clueless that I felt like I was on Mars for the first year and a half or so. But because the people in that lab were so open and helpful, and the PI is an engaged, active teacher, they helped me learn the “language” of biology-type ways of thinking and data/information representation.

It’s that language that you really need as a chemist moving into biology. And by “language,” I mean more than just terminology (although that is a big part of it). It’s also a change in visualization of information and getting better at logic puzzles. Imagine a multi-step synthesis with a blank at step 2, where 4-5 possibilities (which you have assumed based on either mechanism or other times people have done similar things) could fit in there to result in the product (or mixture thereof). In biology, you have to come up with ways to test *which* of those possibilities comes from the retrosynthetic direction (for which you are only postulating a route) and will result in the product(s).

In all of this you also have to accept that: a) your only measurement techniques are indirect, i.e. you usually can’t just analyze the structures with some direct spectroscopic technique and figure out what they are; and b) your assumptions might be wrong. So you have to do lots of control experiments where you also assume some certain set of reagents should DEFINITELY give the products, and some other set should DEFINITELY NOT. That gives you yet another indirect way to make you feel more comfortable with your assumptions. The hardest part for many chemists is having to be okay with indirect information. The second hardest part is having to remember that if your “result” gives you something analogous to “75% yield of the product,” you still have to think a lot about WHAT molecules/interactions are represented in that other 25%. You can’t just purify it away and pretend it didn’t exist.

Getting used to reading gel electrophoresis/Western blot (antibody detection) data, as well as biological “cartoon” format (where you mostly worry about conceptual connections, and not so much molecular mechanism and byproducts etc.), are some great ways to start. But you’ll probably need a coach to guide you through it and translate how the experiments work and what the results mean. Finding friendly, sharp biologists (whether faculty, postdoc or grad student–it doesn’t pay to be snobby about this, sometimes the trainees are gonna be WAY better at teaching you! Just make sure to credit them or repay them somehow!) can be the difference between this working vs. not working.