Sunday, August 28, 2016

Branching Out

Hey readers!

This week, I was given the task of dividing my topic into subtopics to make my lit review easier. At first, I couldn't think of anything to write down, and I was having some issues...

Subtopics = Toby
I decided to study some chess (my favorite sport and theme of this blog post) instead to clear my head. However, when I was calculating moves over the board, I realized that creating subtopics were very similar to analyzing variations over the board! Each subtopic started general and then branched out into more and more specific topics, just like when anyone calculates a bunch of possibilities for chess!

Throwback to my days as a baller... (this picture is publicly available on Google Images)
After a few minutes of thought, I began to scribble furiously on the whiteboard, creating the following concept map of ideas. I had basically outlined the sections of my lit review! As some of you may know, I love drawing maps like this to brainstorm.

Look at how clear and neat it is!
Since my writing on my whiteboard is barely recognizable as English, I decided to proofread and edit the map by making a SmartArt graphic on MS Word. Smart idea, right? I'd have a nice map to put on my blog, show to people like my teacher Mrs. Haag and my mentor Dr. Herbots, and to keep a nice outline of all my ideas throughout the year.

R-O-N-G. After pouring my heart into this flowchart for 15 hours (actually 1 hour), I realized that if I saved the whole map as a picture, a scanning electron microscope would be required to read the text. After several consecutive mental breakdowns and being "triggered" multiple times, I decided to separate each subtopic, so that I could explain them to you guys anyways. So, let's get going!

Subtopic 1: Blood Diagnostics

The most basic subtopic in my project is Blood Diagnostics, as it provides context for HemaDrop when compared to other blood testing techniques and shows the gap in the research/current technology HemaDrop will hopefully fill. We have to look at the evolution (history) of blood diagnostics first to provide context and the purpose/significance to show people why this matters. Next, the goals of blood diagnostics will establish the criteria that HemaDrop will need to meet, as we optimize it throughout the year, and the limitations will specifically discuss the trade-off between volume and accuracy that HemaDrop aims to fill. Finally, comparing liquid (most blood tests) and solid (HemaDrop) types of blood analysis will provide more insight on the properties and potential limitations of both.

Subtopic 2: Super-hydrophilic Films

Next, super-hydrophilic films (SHFs), the technology that enables HemaDrop films to be uniform, should also be investigated. The technical properties of SHFs and nano-particles which create these properties have to be understood to improve the formula for HemaDrop. Additionally, looking at previous work with these films to biomedical technologies is crucial to understand the power of SHFs.

Subtopic 3: Analysis Techniques
HemaDrop can also be improved by increasing the variety of analysis techniques that can analyze the samples. Right now, we have only tried Rutherford Backscattering Spectrometry (RBS) and Particle-Induced X-Ray Emission (PIXE), which identifies elemental composition. Learning more about speectroscopic techniques (basically lasers at different energies which induce an emission of a specific energy based on the identity molecules in the sample) and microscopies will allow for more uses of HemaDrop.

Subtopic 4: Properties of Blood
Since HemaDrop involves drying blood outside of the body, I need to investigate its coagulation properties (how it clots without Heparin or other chemicals which could affect measurements) and properties that affect how it dries on our substrates. Also, the composition of blood (orders of magnitude of compounds/elements that need to be identified) is crucial to understand for optimization. 

Subtopic 5: Substrates
The type of substrate (material below the film) is also a major consideration for its properties that could affect the measurements (conductivity and optical properties), and its cost for if the technology is potentially commercialized.

Subtopic 6: Key Illnesses/Conditions
One idea I had for my methods was to simulate diseases in blood samples by adding characteristic molecules/elements. To do this, I need to identify some key conditions that are prevalent and have a variety of markers/symptoms in the blood. If I learn about the illnesses in my lit review, I can choose which combination to test out.


Woah -- that was a lot of stuff, so I hope I explained them clearly enough! 

Also, I've been reading the books (I got them from the Noble Library at ASU) on the history of blood diagnostics and the properties of nanoparticles. Those will provide some background, along with some articles I found on the importance of blood analysis and microliter blood analysis.

I'll leave you with a silly selfie of me at the lab:




Cheers to another great week of research!
YP

(820)

Sunday, August 21, 2016

Sources Party

Hey readers!

What a week it's been! I've made a lot of interesting discoveries for my research project, and I guess my life -- seeing Seth Rogen's "Sausage Party" (incidentally the theme for this week's post). 

My facial expression after seeing "Sausage Party"
In case you forgot or are joining the party late, my area of inquiry for my project is HemaDrop™, my research group's patented technique for applying blood to a substrate to create a uniform, solid, and thin film analyzable for blood tests, forensics, and other applications. Simply put, the substrate becomes super-hydrophilic (likes water) and sucks up the moisture from the blood, so that it dries in a film.

I'll start with the progress I've made this week. Last week, I forgot to explain why anyone should care about blood analysis and specifically advances in the microliter type. Although I had an idea from previous papers, presentations, and discussions, I delved into the importance of (microliter) blood analysis. Overall, blood testing is crucial for diagnostic medicine, or diagnosing diseases. However, current blood testing requires approximately 7 mL of blood to ensure accurate results.

If you've seen Dr. House in action, you'll understand what I mean.
Microliter blood analysis has many benefits. The primary benefit is the reduced volume required for potentially the same information about patients. Especially for critically ill, very old or very young patients, anemia from undergoing blood tests while in the hospital, aptly named hospital-acquired anemia (HAA), is widespread. HAA affects a MAJORITY of critically ill patients and often causes their conditions to deteriorate, simply from doctors trying to find out what is wrong and monitor their conditions. Additionally, sick patients often already have low hemoglobin (a protein in the blood that carries oxygen) levels, leaving them even more susceptible to anemia.

Even more, the current goals of the biomedical industry are miniaturization and improving quality of patient care. Using a drop of blood acquired from a small prick rather than using an IV or syringe to draw 1000x more blood clearly will improve patient care quality. By minimizing the risks and hassle of tests, potentially more information will also be available for patients and doctors.

The topic of miniaturizing blood volumes for tests is also extremely relevant currently because of the recent Theranos controversy (January 2016). The inappropriate practices of the microliter blood testing company along with the failures of its technology were exposed. Theranos laboratories were diluting microliter samples and providing results over the accepted 10% error threshold. Theranos sold the ideal of personalized and more informed medical care, but without the technology behind it. What had been called a revolutionary technology now is seemingly a fraud (strikingly similar to the "Great Beyond").
Apparently not.

HemaDrop is unique compared to these technologies, as we are using a solid film for analysis as opposed to the traditional blood vial of liquid (pictured above). Using a solid provides many benefits, including more flexibility in analysis techniques and quantitative data not affected by dilution and color of the sample. Thus, my research topic will concern microliter blood analysis and biological applications of super-hydrophilic films -- specifically understanding the properties of HemaDrop even more and optimizing the technology.

My next step is to begin compiling sources and learning about the project. I got a head-start by going to the dark aisle and talking to FireWater about the truth. Actually, when I was working at the lab this Friday, I stopped by the Noble Science Library and picked up two books: one on blood diagnostics (Senses, Sensors, and Systems: A journey through the history of laboratory diagnosis) and another on nanoparticle (Nanoparticle Technology Handbook). Apart from this, I have also received from Dr. Herbots two senior theses of ASU students who worked with other biological applications of super-hydrophilic films. My plan for this week is to read through these to get some background information on clotting mechanisms in the blood, the history of blood diagnostics, and the workings of super-hydrophilic films.

I'll leave you with this image that I took on Friday. It is a picture of two microscope slides -- the one on top treated with a super-hydrophilic film and the one on the bottom untreated. Can you identify the key difference? The answer reaffirms the power of HemaDrop and will be revealed next week!



Cheers,
Yash

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Sunday, August 14, 2016

(Hema)Drop™ It Like It's Hot

Hey readers! Welcome to my blog for 2016-2017 AP Research! 

Since August of 2015, I have had the pleasure of interning for Dr. Nicole Herbots, Professor Emerita in Physics at Arizona State University. When I entered the research group, we were analyzing implantable glucose sensors with Ion Beam Analysis -- shooting ions at them in a particle accelerator to find out what's in it. The goal of these experiments was to characterize the percolation (seeping through) of blood (essentially saline water) into these sensors, which corrupts their internal electronics.

However, around the time of the huge Theranos controversy about blood tests using small drops (microliters) of blood, we realized that we stumbled upon something much bigger. The sensors were simply blood on a substrate, and the same mechanism could be used to analyze blood drops to determine composition. The power of our method was that a uniform film of analyzable blood could be created from only microliters of blood. After rigorous testing using various spectrometric techniques and far too many failed naming attempts, HemaDrop, our method for applying blood to a substrate, was born!
Even Snoop agrees HemaDrop is really cool (or hot?).
Our initial results have been presented in the 2016 Materials Research Society (MRS) Spring Meeting, published in the MRS Advances (you can read the full manuscript here), and submitted for a patent.

Yep, that's me at the MRS Meeting with my poster.
However, much, much, much more R&D must be done on HemaDrop before our method for microliter blood analysis can help patients. Therefore, I will be continuing my research on HemaDrop for my topic this year. 

Since I have finalized my topic, rather than discuss refining my topic, I will discuss the direction I currently foresee the start of my research project taking. 

I'll start by listing 5 important qualities required for microliter blood analysis specifically in the context of HemaDrop:

1. Homogeneity: Since HemaDrop creates a solid film of blood from a droplet and a spot on the film is analyzed, the application method must create a film that has uniform qualities. Any spot on the film should yield the same results when analyzed. One optical quality that clearly shows lack of uniformity is phase separation of a blood film, often seen with one part of the film being clear like the blood's serum and another a reddish purple color like red blood cells.

Look at how uniform those left drops are! This picture is from an experiment done last Friday.
2. Solid: Liquids cannot be analyzed in a vacuum (low pressure), so our film's solid state allows it to be flexible and capable of being used with a variety of analytical techniques from spectrometry to microscopy (more on this later).
A solid Spongebob reference.
3. Thin: The film must be extremely thin, so that the surface analyzed is not different from the inside layers of the film, since some techniques only analyze the surface (a few microns deep) of films.
 We only judge blood films...

4. Cooling Time: Additionally, preparation of time for the samples is crucial ultimately for commercial use and implementation in the biomedical industry. Less time is better, and the properties of the substrate along with surrounding conditions must be investigated and tested to minimize drying time.

5. Conductivity: Although slightly less intuitive (more shocking?) than the other qualities, conductivity is crucial, as how well a sample conducts electricity affects the precision of results and the film's ability to be analyzed by certain methods.

My plan is to start with a literature review about all of the aforementioned qualities to establish their importance and investigate potential ways ultimately to improve HemaDrop.

I'll leave everyone with an interesting problem I also aim to look into next-- our tests so far have used canine blood with Sodium Heparin (an anti-clotting agent) to maintain blood's natural viscosity. However, samples directly from humans will coagulate on substrates without Heparin. We want blood to clot in our bodies to stop bleeding when we get cut, but not on our samples so blood can be analyzable. So, I guess my small (?) task is to circumvent the body's own clotting mechanism to ensure accurate results.

See you next week for more fun, tangentially related gifs, and maybe a discussion on analysis techniques!

Cheers,
Yash

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