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Microfluidics

The primary goal of this project is to develop insight and intuition for transport phenomena in cells by designing and performing experiments to measure these phenomena.

A secondary goal of this project is to introduce the emerging field of microfluidics. Microfluidics refers to the use of devices in which fluid flows are restricted to channels with micrometer dimensions. Such devices are interesting for at least 3 reasons:

In addition, this laboratory project is intended to provide an opportunity to learn about

Mini Research Project

This laboratory project is a mini research project. It is intended to be introductory. No previous research experience is required or expected. However, please be advised that research is very different from conventional homework assignments.

Open-ended. You and your partner will be asked to design and carry out an experiment. A good experiment will lead to insight into some phenomenon that was not well understood before the experiment was performed. Your report will be graded based on (1) the coherence of the experimental design, (2) the reliability of the measurements, and (3) the appropriateness of the conclusions. If your results seem inconsistent with each other or inconclusive, that's bad. It is not important that your results support your preconceived notions or the theories we talk about in lectures and recitations. The first step to making a discovery is realizing when something interesting (i.e., unexpected) has occurred.

Partners. You will be working with a partner in all aspects of this project (proposal, experiment, and report). Properly managed, this can be an enormous benefit. Our experience with projects in 6.021J is that two students can make much more than twice as much progress on a research project than a single student can. We think that the reason for this is that a single student stops at the first barrier that he/she cannot overcome. By contrast, a pair of students stop at the first barrier that neither student can overcome. However, if poorly managed, working with a partner can be a handicap. If you find yourself in this situation, please consult with one of the instructors for help in getting back on track.

Staff. A research project is not like a test. You are not expected to work in isolation. You are encouraged to get outside help, especially from the teaching staff. We want you to do a good project, and we welcome the chance to help you think through your results and plan the next step. If others help you in significant and specific ways (e.g., suggested a new approach), it is imperative that you acknowledge this in an acknowledgements section of your report. For more information about what to acknowledge and how to acknowledge it, see
http://web.mit.edu/academicintegrity/

Experiment Platforms

The experiment platforms for the microfluidics laboratory consist of a microfluidic chamber and a video microscope that is controlled via a computer. Further information about the experiment platforms.

Microfluidic Chambers

Camscope

A computer running Linux is attached to the video camera via FireWire. A program called camscope can be used to view and record images and brightness profiles. Introductory material on how to use camscope. Further information about camscope and associated computer issues.

Choosing a Topic

Begin this by reading through the description of experimental setup, as well as three different experimental platforms shown below. Based on the three platforms, there is a list of sample proposal ideas you can use, or begin with to develop your own ideas.

Finding a partner

You should begin by finding a partner to collaborate for this project. It has been our experience that the quality of the report tends to be higher when the project is done in collaboration. We encourage partnerships between people from different educational backgrounds (e.g. different department), which sometimes leads to more fruitful collaborations. If you are unable to find a partner because you are from an underrepresented department, do talk to us and we will try to find a partner for you.

Control Observations

Control observations are important parts of the design of any experiment. The purpose of a control observation is to determine whether the variable that is directly manipulated by the experimenter is the one that controls the change in response. Two common kinds of control experiments test repeatability (i.e., if you make the same measurement several times, do you get the same answer) and reversibility (i.e., if you make a change and then undo it, does the response go back to what it was before the change), although other control observations are often used. Suppose, for example, that you wish to determine the effect of adding glucose to the diffusion of a dye. You could measure the time-space evolution of dye concentration with no glucose, repeat the measurement with glucose, and compare. If the results are different, can you conclude that the reason is the glucose? What if you inadvertently filled the supply reservoirs differently in the two experiments? Perhaps the difference is because the flow rates were different, not because glucose was added. Control observations are intended to assess the extent to which factors that are not part of the experimental design are contributing to response patterns. Simply repeating the experiment with no glucose is a good way to assess many sources of error. Repeated sequences of measurements can be even better.

Proposal preparation

You and your partner should meet to plan your project and to write a proposal. The proposal should contain a brief statement of the hypothesis / idea you propose to test and the method that you will use to test it. Include a list of the experiments you will perform and the measurements you plan to make in each experiment. Indicate how the measurements will be used to help you test your hypothesis / idea. The proposal should fit on a single sheet of paper. A sample proposal is shown in the following.
Proposal: Linearity of Mixing in Microchambers
Partner Names (E-mail): Partner One (pone@email) and Partner Two (ptwo@email)
Hypothesis: The process by which fluids mix as they flow through microchambers is linear.
Background: The primary mechanism by which fluids mix when they flow through microchambers is diffusion. Since diffusion is a linear process (i.e., the relation between flux and concentration gradient is linear), we expect that the fluid mixing in microchambers will be linear.
Procedure: A laminar flow chamber with two inputs will be used to assess fluid mixing in microchambers. The concentration of dye in the two chambers will be investigated in 3 conditions:
input 1input 2
condition 10%50%
condition 250%50%
condition 350%100%
Mixing will be assessed by analyzing video images of the flow at a point 3 mm downstream from the point where the laminar flow begins. Under the assumption that mixing is linear, the results for condition 3 should be the sum of the results for conditions 1 and 2. To increase the confidence in these results, images will also be obtained at 2 additional locations. The entire experiment will then be repeated to assess effects of uncontrolled variables, such as flow rate.
You should submit your proposal (one for each group) electronically by following the instructions on our home page (http://umech.mit.edu/6.021J/index.html) before 5:00 PM on Friday, September 16. At the time of submission, you are requested to schedule a 2 hour pre-lab session, by choosing the time block of your (and your partners) 1st, 2nd, and 3rd choice. The laboratory accomodates 10 students in each session. You have the best chance to get your most desired time slot by submitting your schedule form early, since the assignment of the slot is first-come-first-served basis. After initial laboratory assignments have been made, you will be permitted to change your laboratory session only if you request the change more than 24 hours before your assigned slot and only if there is an open slot in the schedule at your desired time. The laboratory schedule will be posted on the WWW.

Pre-lab Sessions

Pre-lab session is important because allows you to check the feasibility of your proposal, before you actually do it in a full scale. Before you schedule pre-lab session time read through the experimental setup.

This basic measurement will familiarize you with the experimental setup, in terms of both its capability and limitation. The main purpose of this pre-lab is to revise / improve your proposal, based on the reality / limitation of the experimental setup and the materials provided. Based on the basic experiment you made, you can improve your draft proposal, and make the experimental methods much more detailed. If time permits, you could even try to perform a preliminary experiment by trying to get one data point of your proposed experiment. Maybe you have suggested doing something that simply takes too much time. Maybe you did not know the exact concentration of solutes (or cells) you wanted to try. Fix any problems and make the proposal more realistic and focused, by talking to staff members present during the pre-lab sessions. The successful outcome of the pre-lab session should be a feasible proposal that will be approved by the staff members (TAs / project instructor / other staff members), which should be submitted to the course web site electronically by 5:00 PM on Friday, September 23. At the time of your submission of revised proposal, you should also submit a scheduling request for a 3 hour time block in the lab, to perform the proposed experiment.

Laboratory Notebook

The written record of your experiment is the original record of your work and the basis for everything that you conclude. Such records should be kept in a laboratory notebook, which is typically a special notebook with sewn binding (not a loose-leaf notebook), whose pages were numbered when the notebook was printed. Records should be written in ink. The laboratory notebook is the permanent record of your experiment.

Laboratory notes should be sufficiently detailed so that (1) the experiment could be repeated at some later time, (2) results from different experiments can be compared, and (3) so that your procedures can be reconstructed at a later time without relying on your memory. The first page for each experiment should give the date and time, as well as a brief description of the purpose of the experiment. All relevant procedures and observations should be entered in your lab notebook and the time should be indicated regularly.

Nothing should ever be erased. If an error is detected in some procedure or some reading, that should be noted in the book. The original observation should under no circumstances be obliterated so that it cannot be read. Perhaps you will subsequently find that the original observation was correct and that the correction was in error. The general rule is to write down everything that is done that may later become relevant. Scientists are rarely sorry that they wrote too much in the lab notebook -- only that they wrote too little.

You do not have to purchase a special laboratory notebook for this project. However, we do ask that you take laboratory notes during your experiment, as a step toward learning about effective practices in experimental work. You will be asked to attach your notes to your laboratory report, and we will assess these notes as part of the grading procedure.

Project Report

The project report should be concise. Do not repeat material that is easily referenced. For example, there is no need to reproduce any figure from this laboratory manual or from the course text: simply refer to it. Technical writing is necessarily directed at some particular intended audience. Write the project report as though it were to be published in a journal that is read primarily by students who have taken this subject. Thus, you can assume some working knowledge about the subject. The project report should contain the following sections.

Cover Page. On the cover page include the title of the laboratory session, the authors' names, your laboratory subsection, the dates of the laboratory session(s), and the name of your partner (if not a co-author).

Abstract. The abstract is a one paragraph summary of the report including the question investigated, the methods used, and the principal results and conclusions. Your intended audience (your classmates) should be able to understand the abstract without having to read any of the report. Since it summarizes your report, this section should be written last.

Introduction. The introduction is a brief section (fewer than 350 words) designed to motivate why your findings are interesting and important. The introduction should offer a rationale for your study. One way to motivate interest in your findings is to explain how your study fits within a broader context. For example, you could briefly summarize prior research in this field and argue that there are important unresolved issues (that just happen to be what you studied). Background information is helpful, but extensive library searches are not required. You may give citations to material from this website or elsewhere. The introduction should be directly relevant to your report; broad discussions of microfabrication or biology are not necessary or desirable.

Methods. Briefly describe the methods that you used to obtain and analyze your results. Avoid lengthy repetitions of materials that are easily referenced. Instead, simply provide a citation, such as "Osmotic properties of cells were studied using a microfluidics channel, as described on the lab website [1]." Methods should be organized topically, not chronologically. Avoid "First we did this, then we did that, then we did yet another thing." Break the methods section into subsections, such as "Measuring cell volumes" or "Compositions of solutions."

Results. Describe your technical findings (whether or not they fit with expectations). Generally, results can be communicated more efficiently and accurately with figures and graphs than with words alone. However, a collection of graphs without a written description of their relevance is not acceptable. The text of the results section should carry the reader through a presentation of facts that is intended to lead to a conclusion.

Discussion. Describe the major conclusions from the study. Explain the importance of your results -- especially how they bear on the issues you raised in the introduction section. It is often appropriate to point out limitations of your results (e.g., methodological errors, excessive scatter in results, or low statistical significance). The discussion section can also include relevant speculations and ideas for improving the experiment to test the hypotheses more rigorously.

Appendix. The appendix should include a copy of the notes taken in your lab notebook during the laboratory session. The appendix should also include your critiques from the technical and writing staffs, as well as the critique that you prepared for your peer.

Reports that are written haphazardly and without planning are usually unintelligible and receive poor grades. We strongly recommend that you start by developing a storyboard to structure the logic of the report. Revise your storyboard until the flow of your argument makes sense (ask yourself, "If this were someone else's report, would I believe the conclusion?"). At that point, you can usually write the report by fleshing out the outline.

First Draft / Writing Clinic

The deadline for the first draft is Oct 19th, 10:00am. Please turn in one hardcopy in recitation as well as an electronic copy via the subject website. Only pdf files are accepted electronically.

You will be assigned one first draft from a student peer group to critique. Your critique is due in the Writing Clinic to be held during normal recitation hours on Oct 26. At that time, you will get an opportunity to talk with the staff members (technical and writing) who critiqued your first draft. Final reports are due November 2. Turn in one hardcopy, complete with appendices (described above) plus one electronic copy via the web. One pdf files will be accepted electronically.

Comments on first drafts.

Grading

One of the exciting aspects of experimentation is that even after controlling for serveral variables, unexpected results can occur. In the history of science, many of these unexpected results have led to breakthroughs, precisely because the experimenter started with a clear expectation and got results that violated that expectation. In this project you will propose an experiment and have an expectation about the outcome. You may find that the measurements are straightforward, and that your results match your expectations. However, it is more likely that you will get results that are not consistent with your predictions. Unexpected results are an opportunity, not an impediment.

Throughout this project, keep in mind that you will NOT be judged on whether your predictions were accurate, or whether your measurements are consistent with the theoretical models presented in class. You will not even be judged on whether your final report answers the question posed in your proposal. What you WILL be judged on is your ability to formulate a question, make measurements to address that question, and present a coherent explanation of your results. A report that says "these measurements match theory", when they don't, will likely receive a very poor grade. A report that says "these measurements don't make sense" will score slightly higher. If the report suggests a reason why they don't make sense, the score will be higher still. The best reports will include additional measurements to test this new hypothesis, and show that it explains the observations.

The grade for the experimental project will be based on the proposal and on the project report using the following considerations:

First draft (10%). Your first draft will be graded primarily for completeness.

Critique of Peer (5%). The best critiques make high-level suggestions (e.g., suggesting major restructuring, new figures, ...), ask probing questions (e.g., could your result be explained by ...?), and make low-level comments (e.g., grammar errors, graphical errors).

Report structure (15%). All information in your report should be orgainzed in proper sections.

Clarity and Conciseness of Exposition (10%). A good report is easy to read. The content of each paragraph and each graph should be clear. Everything included in the report should be there for a reason. Points will be deducted for extraneous material. Reports should be less than 10 pages long, unless there are good reasons for additional pages.

Technical Clarity/Conciseness (10%). The techical content should be clear and concise. All technical points should appear for a reason.

Technical Content (20%). The best reports include a thorough investigation of at least one technical topic and contain no technical errors.

Insightfulness (30%). Insightfulness can be demonstrated by (1) proposing an experimental method that can resolve some scientific issue, (2) carrying out experiments and/or analyses that lead to clear conclusions, (3) preparing a report that demonstrates a clear understanding of the strengths and weaknesses of your results and analyses. Simply performing one of the standard experiments and showing unmotivated measurements will receive 0 points. Clever design of an experiment or imaginative analysis of the results will receive 30 points. Demonstrating a clear understanding of your experiment, your analyses, and what can be concluded is sufficient for 15 points.

For more detailed description, you can download the grading sheet for microfluidics projects

DUE DATES ARE FIRM, AND THERE IS A SEVERE LATENESS PENALTY. If you meet the both proposal deadline (9/16 and 9/23), you will get automatic full credit for professionality (5%). Also, if you miss the deadline for the first draft (10/14), you will lose 10% portion dedicated to the first draft. What is worse than that 10% credit is the fact that you will lose the opportunity to get feedback from your peers / staff members, which is a golden opportunity to improve your report.

The grade for a late (final) report will be multiplied by a lateness factor

L = 0.3 exp(-t/4) + 0.7 exp(-t/72)

where t is the number of hours late. The lateness factor is plotted below.

Notice that the maximum grade for a report that is more than ONE DAY LATE is less than 50%.