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)

Could the NanoKids play soccer with a Buckyball?

Well I HAD to take minute to blog this!! Sir Harry Kroto answered my question!

So, those NanoParents better buy some of these NanoCars to drive the NanoKids to soccer practice, so someday they can play in the big leagues!*

*(this particular nerdy joke courtesy of my postdoc advisor)

**anybody else think it is awesome that he proudly displays a mini-Spam wall on his shelf? I would not be surprised to find out that Spam contains C60.

Ask a Nobel Laureate: Harry Kroto

So is running some online media activities through Youtube and Facebook where you get to ask Nobel Laureates questions and they will answer them. Pretty cool, right? The last round of questions went to David Gross, Nobel Prize in Physics, 2004, and you can find more from previous rounds at the Youtube page.

This round features Harry Kroto, one of the chemists who originally discovered the strange but fascinating Buckyball structure of carbon (C60, aka fullerene). Buckyballs have enjoyed much trendiness in the field of chemistry, because they have some weird properties that make them do interesting things with electrons and and interact with other molecules and surfaces in some unique ways. Apparently, they have also been found in space??!! I do not claim to be a C60 Buckyball expert, or even know much about them at all other than that in the early 2000's, if you wrote a grant with the terms "Buckyball" and "HIV" somewhere in the title or abstract, you were pretty much guaranteed to get funded. They were so hot right now. However, these nifty little hollow sphere-like molecules have turned out to be quite interesting and popular, evidenced by the thousands of papers in the literature exploring their physical, chemical and biological properties.

For the "Ask a Nobel Laureate" feature, you submit your questions either by uploading a video to Youtube or in text form--and although a video would be pretty fun to do, given my pseudonymity and lack of time for overly creative pursuits, I'm going to submit mine via blog post cartoon. My question is.... (drumroll..............):

Given the relative molecular scales, if the Nanokids held a World Cup tournament, would they be able to use Buckyballs to play? Or would it end up more like Big Ball Soccer?

Go to the Google Moderator or Youtube site and vote for your favorite question!! (mine, of course!)

My Big Picture (tongue only partly in cheek)

So, I don't currently have a working drawing program on my computer so I have to make a Google Image collage to illustrate my most mostest pulled-back biggest picture, my philosophy of my world on days when I am not OCDing about something stupid that bothers me, my Zen of path through science-human-space.

We each have our little place in it, our little walk through all the possible avenues, and just like vision (and macro lenses) we can only focus on the part right in front of us. Probably it's only practical to expect to clearly see about the next year or two of plan in any great detail. I point myself in the direction I want to go, starting at the "chemistry" paradigm point and going towards the "biology" paradigm cluster. A zoom in on the detail of how I get there would probably look like this:

Except that most of the other nodes around me, and most of the path I had taken and will take would be a lot fuzzier to the eye. A good strategist will learn how to zoom their lens back just enough to see the next set of decisions to make, while keeping active on the current processes until they reach some degree of maturity. Not saying I am a good strategist yet, but I hope to learn how to be one by paying attention to what's going on around me.

So what is everyone's personal goal? Usually to make both their paths and destinations "important." But of course, importance itself has a lot of stochastic elements and the ultimate measure would be to be 'right' about it, right about how this crazy universe/space/world/us REALLY work. But what is "right?" To go really philosophical about it: how do we know it DOES work any particular way and that we're not affecting it just by trying to look? Just because I find some spit on the cat's hair I managed to tweeze out of the box with my incredible intellectual power, I still don't know if the cat is alive or dead or even if it's a cat or maybe a RASCAL that ate a cat...

SO to get back to things that don't wake me up in the night impressing the weight of the vastness of existence on my soul, what I really want to be able to do is maximize my experience at and travel between focus nodes, and not get bogged down with either the nodes themselves, nor the paths the lab ends up taking to them.

For the purposes of communicating as a human with humans, I'm calling this "STUDYING SIGNALING BIOLOGY USING CHEMICAL TOOLS" and we will work towards doing a very good job of making whatever we need to get information about cell signaling that allows us to make more emergent observations about how that stuff is REALLY interacting in there. If I can mature in my strategic abilities, we'll be able to be both thorough and flexible, and not get stuck in the mud of either our tools or our questions while still being able to make both of those things valuable to the overall enterprise of understanding how stuff works, to gradually add elements of information to the drawing until we get a picture of what the whole thing looks like.

To put it an even sillier way, I plan on rolling my chemical biology katamari through the paradigm world and picking up stuff as I go, and hopefully by the time I retire it will be so big I can even stick things like WHOLE PEOPLE and cars and stuff. Right now it is real tiny, so we can only pick up little additional methods and small observations and such, but with some luck and luck I make myself by being sufficiently strategic, it will grow fast enough.

(**you can find the sources for all my images by looking at their links with right click, thanks to the people who gave them homes on the internets for me to find**)