Questioning the Research Question: A Collapsing House of Cards

Hey readers!

After some extensive meetings with Mrs. Haag last week (thank you so much, Mrs. Haag), I figured out how to organize my literature review in a logical and cohesive order compared to my previous blogpost. I came into this class with a set way of thinking about my research from my previous work, which was governing how I wrote my outline. I was having difficulty considering how someone new to the research needed the information presented to understand it.

RIP Bird Gang

Much like the Cardinals this past week, I felt like I had so many chances to win -- to make a great outline -- but I fell short. I threw an interception in the red zone (I'm looking directly at you, Carson Palmer). I couldn't pick up a forced fumble and ended up kicking it out of bounds (Ehem, Tyrann Mathieu). At least I didn't have any fans to disappoint (Wait, but are you, my blog readers, the fans in this complex and extraneous metaphor? In that case, I'm sorry!). Now, the focus moves on to redemption -- the LA Rams and an official literature review outline due 10/7.

In the meantime, I am forming my preliminary research question based on the information I have compiled and the gaps in the research I have found. Here's what I envision for my research question: "To what extent is HemaDrop™ a viable method for determining blood composition by making a uniform, solid, and analyzable film from microliters of blood?"

Here why I decided on this question:

1. Scope: The scope of my research has been quite narrow from the beginning, as I am working  on a specific technology (HemaDrop™). Additionally, this research doesn't start out with the aim to create the perfect formulation of HemaDrop. Instead, the goal is to assess the efficacy of the technology in its current form and provide potential improvements based on the conversation between the literature and the results of the feasibility experiments. In this way, the final product of my research will not be judged exactly on if I create a successful product for microliter blood analysis, as much more will be required than the scope of an AP Research project. 
2. Key Terms:
• HemaDrop™: method for solid-based microliter blood analysis 
• Viable: Provide necessary quantitative information about blood composition including elemental and molecular composition, as a flexible method for creating samples for different techniques. 
• Uniform: different spots on the sample should not yield different compositions. 
• Solid: Only solid films are analyzable in vacuum, which is what most techniques require 
3. Variables: For my experiments, I am testing the viability of the analysis based on the quantitative results. This is the response variable. In my research, the explanatory variable are the properties of the substrate (composition, coating, etc) and the analysis technique. Based on the substrate properties, once the composition of the blood or saline solution is determined, the composition values of they are known could be used to compute the accuracy of the measurements, along with the error. 
4. Research-ability: I had some researchability concerns about the amount of analysis techniques I would have to look into, since I envision my methods creating a bunch of samples prepared in different ways (e.g., type of coating, substrate, etc.). There would be far too many combinations to test. For this reason, after talking to Dr. Herbots (my mentor), I will test 3, or a maximum of 4, analysis techniques (the best ones I determine based on the literature review). I have several sources which describe the advantages and limitations of the analysis techniques. By limiting the number of analysis techniques I will examine, I can make sure that the experiments I conduct are not too many, but also capture the full complexity of the research to come to an insightful conclusion. I see myself answering the question by comparing the results (accuracy, precision, etc) of using analysis techniques on various samples with canine blood, saline, and human blood. The comparison of these techniques will demonstrate how viable HemaDrop substrates are for making a uniform film of blood that can be analyzed by a variety of techniques.
5. Gap: There has been no successful implementation of microliter blood analysis thus far. Theranos has attempted liquid microliter blood analysis, but failed. The limitations of milliliter blood analysis create a clear need for microliter blood analysis, so a clear gap exists in the biomedical industry and in the care for patients. This research aims to fill this void and successfully perform microliter blood analysis. By applying concepts like superhydrophilicity and vacuum-based analysis techniques, HemaDrop aims to create a uniform analyzable film of blood from drops.
6. Significance: The signficance of this research is the creation of microliter blood analysis. The reduced volumes of blood is reduced discomfort in patients who undergo blood testing. Additionally, the problem of hospital-acquired anemia will also be mitigated in critically ill patients. By using less blood, doctors also can test patients more often to assess their diagnosis and monitor their conditions. Finally, the cost of microliter blood analysis will be less than milliliter blood analysis. 

Let's get back to the NFC Championship Game and back to rolling with research!

Cheers,

YP

(863)

The Outline of a Lit Review

Hey readers!

Now that I have compiled about 15 sources about HemaDrop, it's time to start actually outlining my literature review -- it's all business. In case you forgot, I have been using the following subtopics to classify my sources: (1) Blood diagnostics, (2) Superhydrophilic films, (3) Blood Properties, (4) Substrates, (5) Analysis Techniques, and (6) Key Illnesses/Conditions.

Here's what I envision for my literature review:

Subtopic 1: Blood Diagnostics

I have to discuss blood diagnostics in general to introduce the general field of research I am investigating and describe its importance before talking about mechanisms behind blood analysis. Additionally, by explaining the current technology used for blood testing, I can highlight its evolution, needs, and limitations -- basically the gap.

• Premise 1: Blood testing is crucial for diagnosing illnesses, monitoring the conditions of patients, and providing healthcare to patients.
• Barthels, et al: Blood testing is the cornerstone of medicine, as it has allowed for diagnosing of many conditions based on markers in the blood.
• UK National Health Service Database of Illnesses and Blood Markers: E.g., conditions like diabetes, anemia, cancers, heart attacks, etc. all alter blood composition in a specific way, including increased glucose content, lack of Fe, presence of specific biomarkers, elevated troponin concentrations.
• Premise 2: Current blood tests require 7 mL of blood on average.
• Barthels, et al & Hamerling
• Examples include high-performance liquid chromatography (HPLC), spectroscopy of liquid vials of blood, testing conductivity of blood for hematocrit levels, etc.
• Premise 3: The current volume of blood required for testing (7 mL) causes patients discomfort, complications including hospital-acquired anemia (HAA), and can limit the number of tests possible for ill patients (thereby preventing diagnoses too).
• Bom, et al: Better testing procedures and advancements in diagnostics is necessary to stop HAA and unnecessary costs on the healthcare system.
• Thakkar, et al: Current blood diagnostic testing causes HAA, incurs unnecessary cost on the healthcare system, and reduces the quality of patient care. 
• Premise 1 + Premise 2 + Premise 3 --> Conclusion 1: A need exists for blood diagnostic technology that uses smaller volumes of blood to improve patient care, prevent HAA in critically ill patients, and reduce costs.
• Premise 4: Due to the importance of blood analysis, need for standardization, and ease of use needed for doctors and nurses, blood analysis techniques must: "use whole blood and a small sample volume, provide results in less than 1-15 min, maintain high accuracy (at least at current levels), have simple operation and inbuilt quality control, require minimal maintenance,  and use an IT interface."
• Barthels, et al: Point-of-care testing with glucose monitors and similar devices that can provide real-time and accurate monitoring of conditions are part of the next generation of medical devices.
• Premise 5: Previous attempts at blood analysis with smaller volumes (e.g., Theranos) have been unsuccessful.
• Kidd, et al: Theranos had errors of over 10%, the standard for biomedical testing
• Potentially could find more examples?
• Conclusion 1 + Premise 4 + Premise 5 --> Conclusion 2: If implemented, small volume blood analysis (microliter) must meet the aforementioned criteria.
• Premise 6: Both solid and liquid types of blood analysis exist, with liquid requiring little processing and potential lack of uniformity, but with solid allowing for vacuum-based analysis techniques and use of smaller volumes.
• Pershad, et al
• UK National Health Service Database of Illnesses and Blood Markers
• Conclusion 2 + Premise 6 --> Conclusion 3: Potentially a solid-based blood analysis technique, if it overcomes issues with processing time and uniformity, could use small volumes of blood for analysis with vacuum-based techniques.

Subtopic 2: Superhydrophilic Films

The mechanism behind the uniform, thin, solid film that HemaDrop creates is superhydrophilic films (or hyper-hydrophilic if you wish). The explanation of this technology follows naturally after the potential of solid-based blood diagnostics is introduced, since this property is what makes HemaDrop create a uniform film. 

• Premise 7: Superhydrophilic films are created by applying superhydrophilic coatings on surfaces to make them attract water.
• Wen, et al: Superhydrophilicity characterized by high contact angle and high CA hysteresis change by sliding angle -- SHFs can be created by high surface energy coatings and reducing surface roughness (relates to substrates) 
• Hosokawa, et al: "Extremely high receptivity to water adhesion" 

• Premise 8: Superhydrophilic films, because of the importance of polarity have a wide range of biomedical applications
• Hosokawa, et al
• Drelich, et al:
• "For example, surfaces of hydrophilic materials were roughened in the past to improve adhesion in composites, biocompatibility in implant devices, or simply to enhance spreading of liquid, even so these activities were not linked yet to superhydrophilicity" 
• Premise 9: The wettability/hydroaffinity of the surface on which a blood drop affects its uniformity and phase separation.
• Need more support for this -- maybe look at chromatography methods which use a polar mobile phase. (Note: I didn't think of this claim earlier, so good thing I'm outlining!)
• Subpremise 3.1: Since some elements of blood (e.g., the lipid cholesterol) are non-polar, phase separation will occur on hydrophilic samples between non-polar and polar elements.
• Premise 7 + Premise 8 + Premise 9 + Conclusion 3 --> Conclusion 4: The hydroaffinity of a surface can be manipulated to make it superhydrophilic before a small drop of blood is applied. The surface's properties (e.g., surface energy from hydrophilicity) will affect how the blood dries, potentially making the film uniform and analyzable (combatting a major problem with solid analysis of blood)
• Potential Gap -- Determining the optimal degree of wettability to minimize phase separation and heterogeneity, maximize analyzability

Subtopic 3: Blood Properties

Now that we have looked at the coating, we have to investigate the properties of what is actually drying on the surface. Specifically, properties of blood which prevent uniform drying and solid state analysis should be investigated, as they could affect accuracy of measurements or even prevent them.

• Premise 10: Blood contains cells of varying types (e.g., RBCs, WBCs, etc.) that all separate by hydroaffinity and density.
• Palta, et al.
• Can stay unrefrigerated for 24 hrs without separating.
• Premise 11: Blood coagulates in vitro very differently than in vivo, as it uses a cascade of proteins including thrombin, fibrinogen, and protein S, which are activated by Ca ions.
• Acharya, et al.
• Premise 12: Superhydrophilic films limit the aforementioned effects on the blood while preparing a HemaDrop sample.
• Hosokawa, et al & Pershad, et al.
• Premise 10 + Premise 11 + Premise 12 --> Conclusion 5: SHFs can control the natural tendencies of blood to coagulate and separate on surfaces.

Subtopic 4: Substrates

Substrates, although they end up being coated, are extremely important, as many analysis techniques (including Rutherford Backscattering Spectrometry) are affected by conductivity of the sample. Additionally, for commercialization, cost and ease of use are necessary considerations when preparing a sample for analysis. Thus, the, cost, conductivity, and other properties of the sample must be compared to determine the optimal sample type.

• Premise 13 (branching off Premise 7): The hydroaffinity of a surface is affected by the surface topography (roughness). not just the coating, so the substrate affects the degree of superhydrophilicity we are able to achieve.
• Wen, et al.
• Hosokawa, et al.
• Premise 14: Tests have been conducted on TiN/Si(100) and Si(100) surfaces using canine blood with and without the superhydrophilic coatings.
• Pershad, et al: Results published demonstrated a clear difference and affect of the SHF, but the substrates were expensive to use due to their lack of major topographical features (they were smooth)
• Premise 13 + Premise 14 --> Conclusion 6: A more cost-effective alternative, including microscope slides (e.g., borosilicate), should be investigated and the resulting hydroaffinity should be compared after treatment with SHF.
• Potential Gap -- The effectiveness of these more rough surfaces should be tested as an alternative to smoother wafers as tested in Pershad, et al.

Subtopic 5: Analysis Technniques

After looking at the sample preparation mechanisms, it is natural to look into how the samples should be analyzed. A comparison of the limitations, strengths, and properties of various microscopies and spectroscopies will be undertaken to determine which ones to investigate with HemaDrop during experimentation.

• Premise 15: Solid blood samples that are prepared uniformly on substrates can be analyzed in a vacuum, allowing for many applicable microscopies and spectroscopies.
• Mukhopadhay, et al: Describes the conditions necessary for analyzing samples in vacuum
• Premise 16: Atomic Force Microscopy, Scanning/Tunneling Microscopy, IR Fourier Transform Spectroscopy, Ruthterford Backscattering Spectrometry, Particle-Induced X-Ray Emission, X-Ray Photoelectron Spectroscopy, etc. are possible analysis techniques.
• Here's where I realize I need more sources to compare them -- I was having trouble finding good sources that have comparable information about all of them.
• Gap -- which techniques to consider? -- no conclusion yet.

Subtopic 6: Key Illnesses & Conditions

Finally, I want to investigate the specific markers in the blood of several illnesses and potentially simulate the disease in samples to determine whether the difference would be detected. To do this, I found a large database from the UK National Health Service. There are over 1000 illnesses, so to finish off I need to select which illnesses I want to specifically. I don't really have premises here, as I have just looked at diabetes, anemia, various types of cancer, and the monitoring of specific antibiotic concentrations as specific paths to test. I need to find studies who investigated diseases in a similar way that I am, perhaps after they found a new method of analysis.

My research question will then be something along these lines: "Can HemaDrop successfully create a uniform, solid, thin film and accurately analyze blood composition from microliters of blood?” Due to issues with IP, I can look into testing HemaDrop's viability rather than developing the product itself.

Well, I started writing and got very into it. So, there it is. Also, I apologize for no humor. I got too focused on content. Hopefully, I can start attacking the question parts I have outlined. I think if I can fill in those gaps, I'll have a solid understanding of what's going on in my field of study.

Cheers,

YP

(1, 598 -- RIP word limit)

Hospital-Acquired Anemia: A Text Convo

Hey readers!

This week, in class, we looked at John Oliver's most recent episode about charter schools, broke down his argument, and are creating our rebuttals against his points. Apart from the experience being very entertaining, I also enjoyed it because I realized that when I listened to John Oliver, I often simply assumed he was always right because I love watching his show. I guess AP Seminar skills have to applied at all times... My guard will now be up at all times!

Anyways, this week in my research project, I reviewed a lot of sources about current errors in laboratory diagnostics and technology. I also talked to one of my relatives who is a pathologist in the Phoenix area, and she said that I could come tour the laboratory where she works sometime in the next 2 weeks, which is very exciting for my literature review. It has been really hard to find exactly what instruments/techniques hospitals and laboratories are currently using for tests, since they vary so much. However, by looking at what currently is being used, I can establish a criteria for precision, speed, and form for analyzing HemaDrop samples. Since HemaDrop must be at least as good as what is currently available to be viable.

Two sources that I investigated were very very in conversation with each other. They concerned the issue of hospital-acquired anemia (HAA). The relevance of HAA to microliter blood analysis is that HAA often occurs in very sick patients at the hospital, since they require lots of blood testing to diagnose and monitor their conditions. However, these two sources, one a response to another, provide contradicting explanations of the causes of HAA. I somehow got access to their personal, private, and heated text conversation! Here it is! The links to the articles are here (Hospital-acquired Anemia: The Contribution of Diagnostic Blood Loss by Dr. Van der Bom, et al.) and here (Impact of an Educational Intervention on the Frequency of Daily Blood Test Orders for Hospitalized Patients by Dr. Rajiv Thakkar, et al.).

So it seems like these two contradicting sources agreed on the gap in the research -- HemaDrop! I think this conversation is really interesting because it describes the goals of all biomedical research: getting more information from less invasive procedures.

Hope you enjoyed the exclusive convo! I am very excited for this week as I will be hearing back from the pathologist, and I found a great source on analysis techniques.

Cheers,

YP

(673 -- including the text messages, which I wrote as well)

Lit Lit Review: Mini-dabbing or Mini-blood Analysis?

Hey readers!

Happy Labor Day! And we all know Labor Day means two things -- football is back, and it's time to review some literature...

This baby's love of football equals my love of literature reviews?

This week, we learned the essentials of a literature review, I worked on compiling and reading some sources, and the legend of the mini-dab was created. Since both microliter blood analysis and mini-dabbing are compact, smaller, and better versions of original blood analysis and dabbing respectively, mini-dabbing is the theme of this week's post!

Mini-Dab Nation, aka 6th Period AP Research.

Let's first look at my plan for my literature review. Last week, I outlined the subtopics into which my subtopic divides: Blood Diagnostics, Super-Hydrophilic Films, Analysis Techniques, Blood Properties, Substrates, and Key Illnesses/Conditions. These are the main sections I am envisioning for my literature review as well.

By using information about the limitations and consequences of current blood analysis techniques (e.g., hospital-acquired anemia from using large volumes of blood), I can establish the significance of my research with HemaDrop. Also, the subtopics are component parts of the research, which will still allow me to learn a lot and talk about pertinent information even though the research is pretty new and hasn't been explored yet. My plan is to investigate the viability of HemaDrop as a method for microliter blood analysis, but the information I find in my review of the literature on analysis techniques, substrates, and key illnesses/conditions will guide specifically what I will compare in my methods for my experiments.

When your list of goals triggers you hard.

Therefore, my literature review will serve the following purposes (inside the parentheses are the goals of a lit review about mini-dabbing): 

1. establish the limitations of current blood analysis techniques (basically the inadequacies of the current dab), 
2. demonstrate the need for and potential of microliter blood analysis (when you are in a confined space and are triggered), 
3. lay out the necessary criteria that a blood analysis technique must meet to be commercialized e,g., accuracy of current, large-volume methods (what will it take for mini-dabbing to go viral?),
4. explain the mechanisms of HemaDrop including super/hyper-hydrophilicity and phase separation (how the mini-dab mirrors the original dab), 
5. characterize the properties of blood when drying clotting in vitro compared to in vivo (I gave up trying to find parallels here)
6. find out normal/average human blood and canine blood composition  
7. determine pros/cons of various analysis techniques and find analysis techniques (vacuum-based) that HemaDrop samples can be used with to determine new information about blood composition (potentially via computer simulations first before testing),
8. and choose several key illnesses with specific markers in the blood for testing (methods could include comparative testing by adding markers to the blood).

This is also the order I will approach the subtopics in my lit review. One aspect of my literature review I have to be careful about is making sure my sources are in conversation, since the subtopics are all united seemingly only by HemaDrop. 

One specific source which I particularly enjoyed reading and which will definitely help me establish a gap in the research is "Senses, Sensors and Systems: A Journey Though the History of Laboratory Diagnosis" by Barthels and many other authors. "Senses, Sensors, and Systems" provides a thorough history of advances in laboratory diagnostics. I focused on the elements relevant to blood analysis.

First, the sections on blood lines and coagulation diagnostics explain the "cascade-and-arrest" mechanism of clotting of blood. Specifically, it explains all the proteins and triggering chemicals involved (fibrinogen, fibrin, thrombin, prothrombin, protein S, ionized Ca, etc.). The book even discusses the differences between in vivo (in the body) and in vitro (in lab settings) clotting. Next, it discusses near-patient diagnostics (point-of-care testing). For instance, it established the need for rapid identification of troponin concentration for heart attack patients. 

It even provided examples of physical concepts used in POCT. Finally, it discusses the requirements of all microtechnology that is POCT and stipulates the needs of blood diagnostics (use whole blood instead of just platelets or serum, yields quick results with high accuracy, uses small sample volumes, is simple to operate, has in-built quality control and minimal maintenance, and has an IT interface). Also, it cites a lot of articles in references about current methods of blood diagnostics which I had never heard of (e.g., dried blood spot chromatography), so I will look at those as well. Simply, the gap in the research is a device that fulfills those criteria.

Another exciting development is that my dad said he could arrange for me to meet up with/interview a pathologist and phlebotomist at his hospital to find out more about current blood analysis techniques. I'll keep you guys posted on that, as it becomes more concrete, but that information will be crucial for my literature review.

Finally, I'm all in for the John Oliver retort, as it would give us a chance to use our skills from Seminar and Research in a fun, engaging way. I'd be willing to work harder outside of school.

See you next week for some more great research!

Cheers,
YP

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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)

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

(725)

(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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