HVPS for Systems Biology: A Low Cost, High Voltage Power Supply with Schematics + Board Layout

Posted by – June 22, 2009

I have designed this high voltage, low current power supply for various experiments in systems & synthetic biology. I have cleaned up the design and I am placing the schematic and board layout online below!  This circuit outputs up to +1,866VDC at under 1 mA or can be tapped at various points for +622VDC or +933VDC. This is useful for either DIY Biology or institutional research experiments such as:

  • capillary electrophoresis
  • digital microfluidics using electrowetting-on-dielectric
  • possibly electroporation
  • various electrokinetic experiments, such as dielectrophoresis
  • (other uses?? Let me know)
  • and, lastly of course:  making huge sparks that go PAHHHHH-POP

Below is the schematic; read the full post below for the board layout information.  Click on the schematic for the full sized version.  The schematic operates in stages, so leaving out or bypassing before the 2nd final stage will yield only +933VDC, and leaving out that stage will yield only +622VDC, etc.

Schematic for the HVPS "Tripler1"

Schematic for the HVPS

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Don’t Train the Biology Robot: Have the Machine Read the Protocol and Automate Itself

Posted by – June 3, 2009

Imagine reading these kinds of instructions and performing such a task for a few hours: “Resuspend pelleted bacterial cells in 250 µl Buffer P1 and transfer to a micro-centrifuge tube. Ensure that RNase A has been added to Buffer P1. No cell clumps should be visible after resuspension of the pellet. If LyseBlue reagent has been added to Buffer P1, vigorously shake the buffer bottle to ensure LyseBlue particles are completely dissolved. The bacteria should be resuspended completely by vortexing or pipetting up and down until no cell clumps remain. Add 250 µl Buffer P2 and mix thoroughly by inverting the tube 4–6 times. Mix gently by inverting the tube. Do not vortex, as this will result in…” (The protocol examples used here are from Qiagen’s Miniprep kit, QIAPrep.)

Wait a minute!  Isn’t that what robots are for?  Unfortunately, programming a bioscience robot to do a task might take half a day or a full day (or more, if it hasn’t been calibrated recently, or needs some equipment moved around).   If this task has to be performed 100 or 10,000 times then it is a good idea to use a robot.  If it only has to be done twice or 10 times, it may be more trouble than it’s worth.  Is there a middle ground here?

If regular English-language biology protocols could be fed directly into a machine, and the machine could learn what to do on it’s own, wouldn’t that be great?  What if these biology protocols could be downloaded from the web, from a site like protocol-online.org ?   It’s possible! (Within the limited range of tasks that are required in a biology lab, and the limited range of language expected in a biology protocol.)

Biology Protocol Lexical Analyzer converts biology protocols to machine code for a robot or microfluidic system to carry out

Biology Protocol Lexical Analyzer converts biology protocols to machine code for a robot or microfluidic system to carry out

The point of this prototype project is this: there are thousands of biology protocols in existence, and biologists won’t quickly transition to learning enough engineering to write automated language themselves (and it is also more effort than should be necessary to use a “easy-to-use GUI” for training a robot). The computer itself should be used to bridge the language gap. Microfluidics automation platforms (Lab on Chip) may be able to carry out the bulk of busy work without excessive “training” required.

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DIY Digital Microfluidics for Automating Biology Protocols (sub-microliter droplets)

Posted by – June 3, 2009

Systems biologists and synthetic biologists spend a large amount of time moving small liquids from one vial to another. I would say it makes up the majority of their work day, even in a technologically cutting-edge lab which has robotics.  Strange, isn’t it, that the most advanced biological science labs in the world are dependent on a human physically moving small drops of liquid samples and reagents around a lab?

Microfluidics aims to move liquids without humans, under computer control.  A small flow of DNA in water, for example, might trace a path between two glass plates, within a tiny, etched microchannel.  The movement of the flow is controlled by numerous micro-mechanical valves connected to electronics.

Digital microfluidics aims to move liquids without humans, under computer control, using only single droplets under electrical control: no micro-mechanical valves. It works by using electric fields (electrowetting-on-dielectric properties, abbreviated “EWOD”), which polarize water atoms enough to move a very small water droplet across the surface of a computer board.  Droplets on the board can split into two, or join together into one.

Standard PCB etching techniques can be used to make low-tech digital microfluidics devices

Standard PCB etching techniques can be used to make low-tech digital microfluidics devices

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Analog Data Acquisition from USB Microcontroller using the “Processing” Language

Posted by – March 25, 2009

Building on the previous two mini-projects, I have a mini-graphical data acquisition project now running under the Processing language, getting real-world signals from the USB microcontroller (which is a Microchip PIC on a UBW Board from Sparkfun).  Source code below the screenshot.

USB microcontroller sends data to Processing application, which graphs the data

USB microcontroller sends data to Processing application, which graphs the data

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Blinky LED ‘Hello World’ using USB Microcontroller in ‘Processing’

Posted by – March 24, 2009

Every good embedded systems hardware project begins with a blinking LED (or toggling level as seen on the oscilloscope).  In Processing.org language, there’s the opportunity for both, since the built-in graphics allow for data display as well as the USB microcontroller interface.  (There’s several Processing projects for Arduino, BTW.)   Source code is below.

USB Microcontroller blinks happily under Processing.org program

USB Microcontroller blinks happily under Processing.org program

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Using the Processing.org Language with Microcontrollers

Posted by – March 22, 2009

Media-technology engineers at MIT have created a computer language and easy-to-use runtime environment called Processing, hosted at processing.org.  I wrote a small code snip for accessing the PIC microcontroller from a USB port, using Processing; it’s pasted below.

This PIC microcontroller connects to USB on a PC, Mac, or Linux machine

This PIC microcontroller connects to USB on a PC, Mac, or Linux machine

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Apple iPhone 3.0 as next generation Biomedical device

Posted by – March 17, 2009

Apple’s developer preview today, of iPhone 3.0 software, included the interesting news of support for external accessories, either connected through the physical docking connector or through Bluetooth wireless.


A spokesman from Johnson & Johnson announced an iPhone-blood-pressure-monitor accessory, which provides health biometrics and allows the biometrics to be sent over the iPhone’s network connection as an emergency alert.  Their goal is to make diabetes monitoring easier.

The details of the new iPhone interface are in a thin draft document, External Accessory Framework Reference. This doesn’t include the hardware details necessary to connect arbitrary devices, though once it does, I’ll be hooking lots of different devices to the “iPhone-smart-phone-turned-general-purpose-minicomputer”.

I’m sure the game companies already have external joysticks in the works. A recent interview with Pangea software owner revealed their earnings of $1.5 million from downloads of a single iPhone game (Enigmo), with over 800,000 downloads. His biggest complaint: “no D-pad game controller.” Rest assured, that will be solved soon.

Games aside, the iPhone (or iTouch) offers a solid software environment which includes graphical presentation, ease of data entry, network support, wireless roaming, audio support, and now external device data accessories. This is exactly the kind of tool that medical and bioscience needs to help with a deluge of patients.

Synthetic Biology Conference 4.0 videos now online

Posted by – March 15, 2009

Videos of the Synthetic Biology Conference 4.0 from Hong Kong are now available.

One of the best all-around talks as an introduction to synthetic biology, and biotech business aspects of syn bio, is the lecture by Amyris Technologies, and an antidote for malaria using synthesis of the precursors to artimesinin; watch the video below.


Amyris’s Artemisinin Project is completely not-for-profit. The company received a large grant from the Gates Foundation for this commercializable research.

The talk also includes a discussion regarding biofuel breakthroughs now possible through syn bio techniques; their project is currently ramping up to make biodiesel sugarcane bioreactors in Brazil.

Everyone Needs a PCR Machine

Posted by – March 9, 2009

In the early 1970′s, groups of nerdy engineers with hacked-up electronics would meet at “homebrew computing clubs” to share technology and share the vision of a world where “everyone has a home computer for running personal software.”  A couple of these guys like Steve Wozniak and Steve Jobs were part of the tornado, and look around today to marvel at the innovation created. Neither Steve anticipated or guessed that the first personal spreadsheet program, Visicalc, meant for small business and personal finance management, would serve as a catalyst for the rapid rise in adoption of personal computers.

Today, groups of nerdy bioengineers with hacked-up hardware are meeting at “DIYBio” clubs to share technology and share the vision of a world where “everyone has biotech tools for making personal biology.” Mark the calendar: the wave has just begun.

Stanford University: Programmable Microfluidics (2007) – Video

Posted by – March 2, 2009

October 3, 2007 lecture by Bill Thies for the Stanford University Computer Systems Colloquium (EE 380). Bill Thies provides an overview of microfluidic technologies from a computer science perspective, highlight areas in the which computer science researchers can contribute to this field; he will also describe recent work in developing new architectures, programming languages, and CAD tools for the microfluidic domain.



EE 380 | Computer Systems Colloquium:
http://www.stanford.edu/class/ee380/

Make some simple biology lab tools

Posted by – February 3, 2009

Sometimes biology lab tools are really simple, and ridiculously obvious (i.e., a petri dish?).   Yet most of the general public form the idea that biology, chemistry, or even nanotechnology, is impossible because we don’t have high-tech tools. Maybe it’s because the research papers always use big words, half of which are some form of Latin, or the tools are named after a dead guy with a crazy name (erlenmeyer flask anyone?).

Look at some of the tools used in most biology labs for proof.  Cheap office supplies are re-used as laboratory supplies.  Many biology tasks only need the most basic tool for pouring, scraping, mixing, holding, or electrocuting something.  These are easy jobs which only require simple tools.

A few more examples are provided in The Scientist article, Let’s Get Physical -
How to modify your tools to prevent pain at the bench
.   (Free registration might be required to view the article.)

Maybe some of the Makers out there will read this article and Make me something.  (Meredith wants to make something; I need simple lab tools.)

Play Fold.it, the “Tetris-On-Steroids” game that solves protein folding

Posted by – January 29, 2009

“Protein folding” is what again?

It’s this: Foldit (curiously, at the web address: “fold.it”).  And it’s fun to play.  Addictive, really.  Check out the picture:

After I had been playing a while, my 8-year old niece came over to my laptop to see what the cute sound-effects were all about.  After a minute of watching, she said:  “Tell me the web site, I want to play too!”   Yeah, no kidding.

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Build a Spectrophotometer (Schematics included) as a DIY Project

Posted by – December 26, 2008

I recently ran across this published paper.  Most skunkwork types seem to buy used equipment via ebay.    This article explains how to build a spectrophotometer with schematics, illustrations, and photos.  The circuit is simple:  a photoresistor, op amp, and some mechanics for the optics.

The article even includes a Bill of Materials  (component price list); for the electronics, anyway, and it’s cheap (less than $20 for single quantities through Digikey).  The article is geared towards having undergraduate students build their own laboratory equipment as an educational exercise — and if undergrads can do it, anyone can do it (the article says that a science camp of kids aged 13 to 16 found success).

Education in Chemistry

Build your own spectrophotometer

Summary

  • Take a 100 W light bulb, a light-dependent resistor and op amp, a prism or grating in front of a slit, and a curtain – and voilà , a DIY spectrophotometer.
If you build this project or a similar one, leave a comment below.

We Make the News Headlines: “Amateurs are trying genetic engineering at home”

Posted by – December 25, 2008

As a nice holiday surprise for me this week, my project (Melaminometer) & a team member (Meredith L. Patterson) made it into Associated Press science news: “Amateurs are trying genetic engineering at home”.  The article is accurate, and quoted below.  For the melaminometer project, we are also collaborating with Taipei National Yang Ming University.

http://news.yahoo.com/s/ap/20081225/ap_on_sc/do_it_yourself_dna

Amateurs are trying genetic engineering at home

Meredith L. Patterson, a computer programmer by day, conducts an experiment in Meredith L. Patterson, a computer programmer by day, conducts an experiment in the dining room of her San Francisco apartment on Thursday, Dec. 18, 2008. Patterson is among a new breed of techno rebels who want to put genetic engineering tools in the hands of anyone with a smart idea. Using homemade lab equipment and the wealth of scientific knowledge available online, these hobbyists are trying to create new life forms through genetic engineering – a field long dominated by Ph.D.s toiling in university and corporate laboratories.
(AP Photo/Noah Berger)

SAN FRANCISCO – The Apple computer was invented in a garage. Same with the Google search engine. Now, tinkerers are working at home with the basic building blocks of life itself.

Using homemade lab equipment and the wealth of scientific knowledge available online, these hobbyists are trying to create new life forms through genetic engineering — a field long dominated by Ph.D.s toiling in university and corporate laboratories.

In her San Francisco dining room lab, for example, 31-year-old computer programmer Meredith L. Patterson is trying to develop genetically altered yogurt bacteria that will glow green to signal the presence of melamine, the chemical that turned Chinese-made baby formula and pet food deadly.

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The Fundamental Problems in Open Source — What’s the Bio Fix?

Posted by – December 3, 2008

Synthetic biology aims to create biological parts which can be connected together to form larger functional devices, and many hope the most poplar library of parts will be “Open Source”.  Openly publishing large collections of biological parts is great, as it would rapidly accelerate engineering progress and rapidly diseminate the technology.

There’s one big drawback to open source though:  Where do you go when it doesn’t work? This is called the support issue. Presumably, there’s a “community of experts” who monitor problems and provide fixes for others. More often, though, the users themselves have to become expert, or they abandon the project.   (A secondary question is:  Who do you sue when it does something wrong? which is a question I posed in my licensing discussion.)

I recently ran across the following blog article from a popular web hosting company (bluehost.com) describing their use of Linux (properly called GNU/Linux, since Linux is only a small part of the operating system, and a tapestry of GNU software makes up more than 90% of a “Linux system”).  This web hosting company is very popular with many individuals and small companies, and it’s profitable existence owes much to open source software (although it’s reported that their servers experience unhealthy downtime).  Without open source software, the company couldn’t exist; the cost of their software would make their service very unprofitable.

The following quote is telling [1]:

“Whenever we see ANY bottleneck in the system whether it be CPU, I/O Block Device, Network Block Device, Memory, and so on we find out EXACTLY what is causing the problem. When I say we find the problem, I mean we go down to the actual code in the kernel and see exactly where the issue is. Sometimes that gives us the answer we need to the solve the problem and other times it is a bug in the kernel itself that we need to create a patch for.” (The full article is quoted below)

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Average Americans are Scared of “Synthetic Biology”

Posted by – November 20, 2008

Yes, believe it, non-synthetic biologists have a poor, even fearful, associations when synthetic biology is described to them:

Q: How do the descriptions of these technologies [synthetic biology] make you feel?

Female Respondent: I really thought of sci-fi movies, where, um, something is created in a laboratory, and it always seems great in the beginning, um, but, down the line, something goes wrong because they didn’t think about this particular situation or things turning this way.

Male Respondent: The “Jurassic Park” movie came to mind.

Female Respondent: It’s scary, why do we need to have new organisms? Why do we need to have, you know, you know, genetic engineering? Does it really help with anything? It’s really, it’s not going to help a common person like us. I don’t think, it’s not going to be for helping any of us.

Watch the video for yourself — promise, though, that you won’t throw your mouse at your screen:
Nanotech and Synbio: Americans Don’t Know What’s Coming: “This survey was informed by two focus groups (video – focus groups) conducted in August [2008] in suburban Baltimore [by The Project on Emerging Nanotechnologies Synbio Poll]. This is the first time—to the pollsters’ knowledge—that synthetic biology has been the subject of a representative national telephone survey.”

One of the men states he’s a biologist, and later says, “Who’s playing god here? Who are we as humans to think we can design or redesign life? It’s nice to be able to do it but is it right?”

While watching the video, keep in mind the benefits and limitations of focus groups (wikipedia: Focus groups).

Genetically Engineer Bacteria and/or Yeast using Sound (Ultrasound, Sonoporation)

Posted by – November 20, 2008

Almost everyone in the BioBricks realm seems to use a standard method for modifying their organisms: chemical transformation. Yet there is another method which is very promising.

In chemical transformation [3], some standard bacteria is grown, purified, mixed with some chemicals which cut open the bacteria, the new DNA plasmid is added to create some modified bacteria, the new DNA plasmid flows through the cut into the bacteria, everything is mixed with some more chemicals, allowed to heal & grow, and purified. (My naive translation of the process)

Note all the chemicals used? Chemicals can be expensive. And the amount of modified bacteria which results from this process is pretty low.

There’s an alternative method used more for yeast than bacteria: voltage-based transformation, electroporation [1]. With electroporation, some standard bacteria is grown, mixed with some simple chemicals, the new DNA plasmid is added, everything is given a quick high voltage zap (like lightening) which cuts open the bacteria, the new DNA plasmid flows through the cut into the bacteria, the bacteria is allowed to heal & grow, and purified.  (Again, my naive translation of the process)

This eliminates some chemicals, although the process still requires some specialized equipment which can be troublesome (and expensive) — the voltage can be as high as 5 kV at 20 mA. (As high as the internal components of a CRT television, which, if accidentally touched, can be easily fatal.)

There’s another method though, that I haven’t seen mentioned: sonic transformation, sonoporation [2]. In sonic transformation, some standard bacteria is grown, some chemicals are added, optionally producing small bubbles, the new DNA plasmid is added, everything is given a loud blast of ultrasound (for example, at 40 kHz) which cuts open the bacteria, the new DNA plasmid flows through the cut into the bacteria, the bacteria is allowed to heal & grow, and purified.

In the research quoted below, sonoporation has shown to be much more effective at modifying bacteria than either chemical transformation or electroporation; plus, this is done without the expensive chemicals necessary for chemical transformation and without high voltage equipment necessary for electroporation.

From [2]:
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Skunkworks Bioengineering — Prerequisites to Success?

Posted by – November 13, 2008

“Despite all the support and money evident in the projects, there is absolutely no reason this work could not be done in a garage. And all of the parts for these projects are now available from the Registry.” Rob Carlson, iGEM 2008: Surprise — The Future is Here Already, Nov 2008.

The question which should be posed is:

  • What does it really take to actually do this in a garage?

Of course I’m interested in the answer.  I actually want to do this in my garage.

(Let’s ignore the fact for a moment, that many of the iGEM competition projects don’t generate experimental results due to lack of time in the schedule, thus actual project results don’t mirror the project prospectus.)

Here is my short list of what is required:

  • Education (all at university level)
  • Experience
    • 1 year of industry or grad-level engineering lab research & design
    • 1 year of wet lab in synthesis
    • 2 more years of wet lab in synthesis if it’s desired to have a high probability of success on the project (see my SB4.0 notes for where this came from)
  • Equipment
    • Most lab equipment is generally unnecessary, since significant work can be outsourced.
    • Thermocycler
    • Incubator
    • Centrifuge
    • Glassware
    • Example setup: See Making a Biological Counter, Katherine Aull, 2008 (Home bio-lab created for under $500.)
    • Laptop or desktop computer
    • Internet connection
  • Capital
    • About $10k to $20k cash (?) to throw at a problem for outsourced labor, materials, and equipment (this cost decreases on a yearly basis).
  • Time (Work effort)
    • Depends on experience, on the scope of the problem, on project feasibility — of course.
    • 4 to 7 man-months to either obtain a working prototype or scrap the project.

Although some student members of iGEM teams are random majors such as economics or music, somehow I’m not sure they qualify towards the “anyone can do this” mantra.  Of the iGEM competition teams who placed well for their work, all of the members were 3rd year or 4th year undergrads or higher.  The issue isn’t the equipment or ability to outsource — it’s the human capital, the mind-matter, that counts: education and experience.  (Which, in the “I want to DIY my Bio!” crowd, is a rare find.)

With all that covered, it seems anyone can have their very own glowing bacteria.

“Biology is hard, and expensive, and most people trained enough to make a go of it have a lab already — one that pays them to work.”   — Katherine Aull (see above ref.)

Modifying Yeast for Drug Production in Beer – BioBeer

Posted by – November 13, 2008

How synthetic biology gets done in iGEM competition:


Jam08 Live: Rice – BioBeer from mac cowell on Vimeo. [1]

Before getting too excited though, keep in mind:

  • The experiment hasn’t been verified to work. The yeast “seems to be consuming some intermediate products” however the drug production hasn’t been verified.
  • The benefits of resveritrol may be dramatically overstated. It may take very large quantities of resveritrol to have any health benefits [2].
  • The public-at-large has responded very enthusiastically to this idea (same with the modified yeast for Bio Yogurt) — which may signal the tempering of the typical U.S. “No GMO!” paranoia. Random people have proclaimed: “I want to drink this beer!”, casting aside concerns of consuming genetic engineered products.
  • The most remarkable health benefits in both wine and beer may be due to the alcohol (reducing psychological stress); it seems no one (?) has a good study on this because no one studies non-alcoholic wine or non-alcoholic beer.
[1] Jam08 Live: Rice – BioBeer from mac cowell on Vimeo. Filmed by http://www.vimeo.com/macowel
[2] Beer: The Best Beverage in the World. Charlie Bamforth, Ph.D., D.Sc. of University of California, Davis, at PARC Forum. March 22, 2007. Watch the Video as wmv  Charlie Bamforth is Fellow of the Institute of Brewing & Distilling and Fellow of the Institute of Biology, Editor in Chief of the Journal of the American Society of Brewing Chemists and has published innumerable papers, articles and books on beer and brewing.

Computational Biology for Discovering Protein Function – as of 2008

Posted by – November 12, 2008

“The vast majority of known proteins have not yet been characterized experimentally, and there is very little that is known about their function.” [1]

A paper just published (Nov 2008) in PLoS Computational Biology describes the fundamental problem of proteins in biology.  It is “the dogma” that the DNA sequence is transcribed and translated to protein sequence; related to this, the protein sequence dictates a protein structure, and the protein’s structure (physical shape) dictates the protein’s function.  Want something biological to work?  Find the right protein shape that, for example, physically fits to the drug.

Except there are big problems here:  the structure can’t be easy predicted from the sequence, similar sequences can have vastly different structures (homologous -vs- non-homologous), some proteins have multiple functions in different environments even with the same structure, similar structures can have vastly different functions, and the different functions are often related to very small changes in structure!  Meanwhile, the catalog of proteins is growing every day, and the lab’s can’t keep up with experiments which highlight a protein’s function. So what’s a bioengineer to do?

The article, The Rough Guide to In Silico Function Prediction, or How To Use Sequence and Structure Information To Predict Protein Function, is a good summary of the issue.

  1. “the most common way to infer homology is by detecting sequence similarity”
  2. Sequence similarity is usually done with sequence alignment.
  3. “homology (both orthology and paralogy) does not guarantee conservation of function”
  4. “databases contain incorrect annotations, mostly caused by erroneous automatic annotation transfer by homology”
  5. “homology between two proteins does not guarantee that they have the same function, not even when sequence similarity is very high”
  6. “a relatively small sequence signature may suffice to conserve the function of a protein even if the rest of the protein has changed considerably”
  7. “Residues that have similar function in different proteins are likely to possess similar physicochemical characteristics.”

Biology research also currently can’t figure out why nature has employed some proteins but not others, even when it has been experimentally verified that artifically created (synthsized) proteins can be substituted into natural processes successfully [2].  So if no rules dictate the mapping between protein and function, then how can functions or structures be reliably predicted?

The current shotgun method is to use multiple methods of determining similarity (sequence, structure, binding sites).  Although not mentioned in [1], I assumed electrostatic mapping might also be used, though maybe this hasn’t provided useful results.

[1] Punta M, Ofran Y 2008 The Rough Guide to In Silico Function Prediction, or How To Use Sequence and Structure Information To Predict Protein Function. PLoS Computational Biology 4(10): e1000160 doi:10.1371/journal.pcbi.1000160
[2] Chiarabelli, C.; De Lucrezia, D., Question 3: The Worlds of the Prebiotic and Never Born Proteins, Origins of Life and Evolution of Biospheres 2007, 37, 357-361.  See also, The Emergence of Life: From Chemical Origins to Synthetic Biology by Pier Luigi Luisi.