small biz synbio
Neil Eastep
I know that open source is the modus operandi at DIY bio, and I have
no wish to take that away. I wonder, though as synbio "grows up" what
are some small business ideas that a university student could create
with synbio? (on a university student's budget).
Not "giant" firms like Venter's Synthetic Genomics .. . but legitimate
small biz that allows a combination of
making-money-to-put-food-on-the-table and an interest in synbio?
What are the markets available to small biz synbio?
a) How does one protect intellectual property on a zero budget? Can
defensive publishing do the job?
b) I am assuming that some form of the minimal cell concept would be
involved here . . .
sorry if I sound like a novice here; I am.
Neil
Meredith L. Patterson
both open hardware and open synthetic biology, a product still has to
be made. Some people are hardcore enough (and have access to good
enough facilities) that they'll fab their own PCBs, buy components
themselves, and so on and so forth, sending no money back in the
direction of the inventors. Some people want to buy a kit and solder
it together themselves, and the inventor can make some money off that.
Some people just want the device and are happy to pay for it. (Of
course, in the latter two cases, it's in the inventor's best interest
to pair up with a reliable, low-cost fab house so as not to get
undercut by third parties!)
Synthetic bio strikes me as exactly the same scenario. Some people are
hardcore enough (and have a good enough lab) to synthesize an
interesting sequence, PCR themselves a bunch of copies, insert it into
a vector, and transform some bacteria or tissue. Some people will buy
pre-made plasmids. Some people just want a particular strain to work
with and are willing to pay for it.
Open source certainly doesn't imply "unfriendly to business", and
indeed, I think the opportunities for open-source biology are broader
than those in open-source software.
--mlp
David Bryson
>
> I'd look for parallels with open hardware projects such as Arduino. In
> both open hardware and open synthetic biology, a product still has to
> be made. Some people are hardcore enough (and have access to good
> enough facilities) that they'll fab their own PCBs, buy components
> themselves, and so on and so forth, sending no money back in the
> direction of the inventors. Some people want to buy a kit and solder
> it together themselves, and the inventor can make some money off that.
> Some people just want the device and are happy to pay for it. (Of
> course, in the latter two cases, it's in the inventor's best interest
> to pair up with a reliable, low-cost fab house so as not to get
> undercut by third parties!)
Yeah I agree entirely, for example the homebrew stirplates that the
brewing community likes to make. The options are basicly: built it
yourself with $35 worth of parts and some electronics knowledge, or but
a commercial one for hundreds of dollars.
There is definitely a market for somebody to provide these people with a
stirplate for under $100 made from jameco parts.
Obviously this could be expanded to other types of devices and services.
Dave
Meredith L. Patterson
>
> On Wed, Oct 29, 2008 at 02:40:20PM -0700 or thereabouts, Meredith L. Patterson wrote:
>>
>> I'd look for parallels with open hardware projects such as Arduino. In
>> both open hardware and open synthetic biology, a product still has to
>> be made. Some people are hardcore enough (and have access to good
>> enough facilities) that they'll fab their own PCBs, buy components
>> themselves, and so on and so forth, sending no money back in the
>> direction of the inventors. Some people want to buy a kit and solder
>> it together themselves, and the inventor can make some money off that.
>> Some people just want the device and are happy to pay for it. (Of
>> course, in the latter two cases, it's in the inventor's best interest
>> to pair up with a reliable, low-cost fab house so as not to get
>> undercut by third parties!)
>
> Yeah I agree entirely, for example the homebrew stirplates that the
> brewing community likes to make. The options are basicly: built it
> yourself with $35 worth of parts and some electronics knowledge, or but
> a commercial one for hundreds of dollars.
Hey, do you have plans for one of those, and do they provide heat?
I've been looking for a stirring hotplate and you're exactly right, I
don't want to pay hundreds of dollars for one.
--mlp
Norman Wang
what the current market offers. (e.g. I cannot find one that has
excitation light source built-in other than the stupid eGel that force
you to fill the trash with expensive plastic waste; some people want
cameras mounts, or devices that facilitate easier gel extraction) It
seems simple enough to build using off the shelf materials: pieces of
cut acrylic, blue 470nm LED, platinum wires that can be purchased from
TAP Plastics, eBay, and A-M systems respectively. The major initial
cost for individuals is the time it takes (for research and building
prototypes) per few final units produced. If enough DIYBioers are
interested, it may be possible to do a group-buy for cut to size parts
that each of us can assemble ourselves in the lab.
A small business could come in and offer these as "parts" or "pre-
assembled", at a cost competitive to the current monopoly in basic gel
box market. Large companies through the distribution channel monopoly,
don't have much incentive to improve the basic gel-electrophoresis
box, let's give'm a run for their money.
Gel separation, hotplate, & PCR are so basic and crucial to many
aspects of molecular biology, I think it could develop like how the
Mountain Bike industry developed through the 70'-80's (please read up
on wikipedia if you are unfamiliar with that). There is very little
need to protect "intellectual property" with a DIY modular opensource
standard on a technologies as basic as these.
Let's see how this "M'Kenzie in the Kitchen - how to make a gel box"
video goes... I'd be interested in investing in a venture selling the
kits.
Norman
On Oct 29, 1:04 pm, "Meredith L. Patterson" <clonea...@gmail.com>
Jim H
With regards to protecting your IP, there are a couple things you can
do:
If you publish your results in an open access or peer reviewed
journal, they become "public domain" which means the method/product
cannot be patented, but also means that anyone can copy your protocol
and make it.
A better plan is to protect the "methods" through "trade secrets".
You just don't disclose your methods, formulas or key processes. You
can always give the public/customers the general outline, but hold
back one or two key bits of information the results in the product of
interest. This is done all of the time and doesn't cost you a dime
(unless you have a bunch of employees when it usually benefits you to
pay them to keep their mouths shut).
Jim H
I am a small business owner and I also just happen to have worked at
the company that was devoured by the mud sucking dogs at Invitrogen.
A couple of friends/business associates of mine just happen to have
been the people who developed the old BRL submarine gel boxes,
sequencing apparatus etc. We know the plastics group that probably
still has the plans and I think lost the business when IVGN came in.
A friend of mine still uses them for his apparatus production. I'll
talk to them and see if they'd be interested in cutting some parts and
what the general costs for that would be.
We could copy the IKEA model for making gel boxes.....
On Oct 30, 7:26 am, Norman Wang <analo...@gmail.com> wrote:
> I would like to build a simple modular gel box that is better than
JonathanCline
trained expert in a very narrow niche market, by openly publishing
intellectual
property. This is done out of personal interests, not for profit.
Then, if
the author is very lucky, some big companies sign him on as either a
design consultant or a contractor on a specific project. The
companies do
this because the author's components are so niche that no other
expertise
exists (sometimes in the entire world). So it doesn't benefit the
company
to re-invent the wheel for a small component.
For example in operating systems, some open source drivers are only
written by very specific people. Also specific libraries.
And by the way, the open source solutions are usually not very good
solutions. They are buggy -- only the authors know the work-arounds
for the bugs; the code is very difficult to understand -- only the
authors understand how it works; and there is little or no
documentation
for the product -- only the author can make improvements reliably.
The difficulty of improving or using the product due to lack
of documentation creates the trade secrets which allows the author
to leverage his skills.
One example is the C library, uclibc. The code is open source under
LGPL (meaning, you can use it without it affecting your code, but
you can't modify it without releasing the modifications).
Documentation
doesn't exist other than a list of functions. Making bug fixes is
not
profitable. The code has little comments and is very difficult to
read. A couple years ago there were significant errors which made
the functions completely fail in particular environments -- also
undocumented. However, this software is used in many netgear
wireless network routers because it was a critical component that
was needed, and the company contracted the authors to fix the
environment related bugs. They received normal level of salary
for a few years.
In bio, I can see a clear analogy. Become an expert in a particular
microbe, or particular set of biobricks, out of your own interest in
synth bio. Hope that this microbe becomes a critical need in the
market place (maybe it has specific environmental conditions or
etc). Critical need, to me, usually means that the companies
aren't aware that it is needed during business negotiations,
yet much later in the design, it becomes a critical "must have this
solved now" kind of problem. (Which I would also say is a
very bad oversight problem in project management.)
In your work, spend more time doing research & design than
documentation, so that no one can really understand how the
niche technology works -- open source naturally tends this
way, towards lack of good documentation, so this shouldn't
be too hard.
Keep in mind though, there are far more open sourcers out
there who don't make any money at all from their efforts,
because the niche never materializes into the "company
must have". Or the niche blossoms with an avid community,
so it's no longer a niche, and is well-supported by others,
thus reducing the ability to get paid to work on it.
## JonathanCline
## jcl...@ieee.org
## Mobile: +1-805-617-0223
########################
Josh Perfetto
while there are lots of applications around food, crops, and health, the
regulatory hurdles to overcome are quite high and put this out of budget for
a small company. There's certainly some amount of opportunity around
alternative hardware/tools as others have suggested to accommodate the lower
end of this emerging industry.
In terms of biologicals themselves, I think tools for the biotech industry
to make an existing process better/enable a new process would be very
doable. I was also thinking about non-medical diagnostic tests (e.g.,
detecting an environmental contaminant in water). For example, there was an
iGEM project on a biological arsenic detector. A lot more work would need
to be done to commercialize something like that, but the point being that
there is a need to drive testing costs lower than existing methods (for
performing frequent tests in developing world drinking wells). There are a
number of chemicals you might want to detect, including some that may have
first-world applications. It might be possible for a group of people here
to work together on commercializing some sort of test.
Actually, a question I have when it comes to these sort of tests is whether
there are existing distribution methods. I.e., if you have a test which
depends on a live microorganism, all other problems aside, is there a way to
package and distribute this cheaply (for example, without requiring
refrigeration)?
-Josh
Meredith L. Patterson
> Actually, a question I have when it comes to these sort of tests is whether
> there are existing distribution methods. I.e., if you have a test which
> depends on a live microorganism, all other problems aside, is there a way to
> package and distribute this cheaply (for example, without requiring
> refrigeration)?
Depends on the microorganism. In any pharmacy or health food store,
you can buy Lactobacillus acidophilus tablets; the ones I have
advertise over a billion live organisms per tablet. I have
successfully cultured from these before. The tablets also contain
cellulose, calcium and magnesium stearate.
--mlp
Jason Morrison
http://www.wired.com/techbiz/startups/magazine/16-11/ff_openmanufacturing?currentPage=all
and (b) chime in on a few points than Jonathan brought up.
While much open-source enjoys a smattering of bugs and loneliness through hard-to-understand code, docs, and architecture, it's worth pointing out that this is far from ideal. To have many people tailor your open-source project to solve their problems, and hopefully (!) contribute these modifications back, it is necessary to be clear and understandable.
I believe that this is a very useful measurement of "success" in an open-source project, and that it's worthwhile to consider how crucial it is to (1) ramp people up quickly on your project, (2) help people solve their own problems through truly awesome documentation (be they videos, tutorials, books, a clean and well-commented code base, a logical architecture, or all of these), and (3) make the contribution process super simple.
Cheers,
-Jason
P.S.: Interesting exercise to check out the volume of developer documentation for Rails, Firefox, and Apache, as well as the comments:code ratio (~19%, 22%, 28% comments by lines-of-code, respectively, by ohloh.net)
Jason Morrison
jason.p....@gmail.com
http://jayunit.net
(585) 216-5657
Josh Perfetto
doing this with E. Coli is basically ok, or would there be viability
problems upon rehydration?
-Josh
Jim H
It doesn't seem to work as well for e. coli. Not exactly sure why,
but I'm sure there is a bona fide microbiologist amongst us.
InvivoGen sells lyophilized comp cells:
http://www.invivogen.com/family.php?ID=189&ID_cat=7&ID_sscat=93
I would think it should work with any e coli
On Nov 1, 8:39 pm, Josh Perfetto <j...@snowrise.com> wrote:
> Interesting, are they lyophilized or actually live? Does anyone know if
> doing this with E. Coli is basically ok, or would there be viability
> problems upon rehydration?
>
> -Josh
>
Jim H
stable only 6 mos @ -20 C.
> doing this with E. Coli is basically ok, or would there be viability
> problems upon rehydration?
>
> -Josh
>
Jim H
claims of room temperature stable e coli by "beaching" the e coli in
agar. The agar seemed to stabilize the e coli, even when dessicated.
I was doing mammalian cells, so wasn';t real interested in claims they
made. Like I said, they are not in business anymore, but I know where
their principle scientist resides.
But if you are using yeast, then dessication is not an issue.
Josh Perfetto
cells, I'm wondering if when they say stable, they are really concerning
themselves with the competence of the cell which may be lost before
viability.
I also found this
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=92041 which
suggests that tolerance for desiccation and lyophilization may be
engineered. At any rate it's good to know that there are multiple
possibilities here, and making this work may be an important SynBio project
in itself.
This was just one idea of what a small company may be able to work on, would
love to hear others' thoughts.
-Josh
Meredith L. Patterson
>
> As for the InvivoGen
> cells, I'm wondering if when they say stable, they are really concerning
> themselves with the competence of the cell which may be lost before
> viability.
I'm not sure, though I bet you could email or call them and ask --
they no doubt have to field questions like that all the time. Still,
making E. coli competent is not particularly difficult; all you really
need is some calcium chloride, which can be purchased easily. Hardware
stores in climates that get snow will have it as a de-icer, or if you
live someplace warm and don't want to order it from a supplier, you
can make it in a pinch from calcium carbonate -- available at any pet
store that sells reptile food, you sprinkle it onto crickets so that
your reptiles get the calcium they need for bone health -- and
hydrochloric acid.
(If you decide to make your own calcium chloride, DO IT SOMEPLACE WELL
VENTILATED. I cannot stress this enough. A kitchen vent is not
sufficient. I learned this the hard way and had to be carried out of
my kitchen. The reaction outgasses CO2 quite rapidly.)
--mlp
Josh Perfetto
realize people were taking DIY so far. How successful were you in your
transformations?
-Josh
Meredith L. Patterson
some water in it and we didn't want to take it apart. It worked quite
well, actually.
So far, I've been working with L. acidophilus, which is kind of a
difficult bug to work with -- it doesn't respond well to heat shock.
It's supposed to be possible to use heat shock on lactic acid bacteria
by treating them with magnesium chloride and calcium chloride to make
them competent, then performing the heat shock in polyethylene glycol
solution, but so far I haven't gotten that to work. (I've only done it
once, mind.) Everyone I've talked to has told me that electroporation
is really the way to go for Gram-positive bacteria, so I'm building an
electroporator. I've built out the control logic (prototyped on an
Arduino, though I intend to design a PCB that uses an Atmel
microcontroller once I get this working), and I've designed the HV
side of the apparatus (using a 3kV neon sign transformer as the
voltage source). The transformer puts out AC, so I need to get some
more HV diodes to build a rectifier, then wind a choke and get some HV
resistors to get the voltage down to 2.5kV. I also need to pick up
some HV probes for my oscilloscope to make sure that the pulse being
put out is a nice clean square wave.
If I had some E. coli, I'd definitely try heat shocking them, but I
don't have an appropriate freezer. Working on solving that problem,
too.
--mlp
John Cumbers
John
John Cumbers, Graduate Student
NASA Ames Research Center
Mail Stop 239-20, Bldg N239 Rm 373 Moffett Field, CA 94035, USA.
cell +1 (401) 523 8190, fax +1 (650) 604-1088
Graduate Program in Molecular Biology, Cell Biology, and Biochemistry
Brown University, Box G-W Providence, RI, 02912, USA
Meredith L. Patterson
freezer? If so, they really will be ideal. I'm looking forward to a
review of the book!
Does anyone know if ATCC will ship to individuals? It would be nice if
we could develop our own cell lines, but doing so from an established
line might be tricky from a legal POV. Last time I checked into Steve
Kurtz's situation, the only thing the government was still hassling
him about was the fact that he got his cultures from someone else who
had ordered them from ATCC and violated the material transfer
agreement by giving them to him.
And sure, I'd be happy to do a video about the electroporator, just
let me get it working first. :)
--mlp
Tom Knight
the past four years. I believe the ADP1 strain is european in origin,
and there should be many labs that have it without ATCC MTAs.
The historically important way of storing strains for long periods was
with "stabs", which are small tubes filled with agar medium. Stabs are
made and sterilized, then inoculated with a needle to infect the
culture. The stab is then cultured for a day or so uncapped until
replication starts, then sealed tightly and held at refrigerator
temperature for long periods (1 year +). There can be genetic drift in
these, and some may die, but this was the common strain maintenance
technique for decades. Reculturing every year or so is essential.
Some strains don't respond well to this treatment, and it has almost
been abandoned in favor of -80 storage. Find an old microbiology
textbook.
Please don't kill yourself with the high voltage power supply. The
electroporators use a (mechanical) relay to charge a capacitor on an
internal high voltage supply, then transfer the capacitor to the output
wires. There is a high value bleeder resistor across the capacitor to
remove charge when the unit is powered down. It's easy to make
something that is quite dangerous with 2-3 KV power supplies if you
don't know what you are doing, and they can stay dangerous even if
unplugged.
Meredith L. Patterson
> Please don't kill yourself with the high voltage power supply. The
> electroporators use a (mechanical) relay to charge a capacitor on an
> internal high voltage supply, then transfer the capacitor to the output
> wires. There is a high value bleeder resistor across the capacitor to
> remove charge when the unit is powered down. It's easy to make
> something that is quite dangerous with 2-3 KV power supplies if you
> don't know what you are doing, and they can stay dangerous even if
> unplugged.
Thanks, but you're telling me stuff I already know. :) I'm actually
using HV power transistors rather than a capacitor because HV
capacitors are expensive and hard to find. The HV side of the circuit
is optoisolated from the 5V side, and I'm using high-voltage lead wire
and insulating all my joins. I've also run my design by a couple of
guys who have been doing electronics design far longer than I have,
and they've all given it a safety thumbs-up.
Now, that said -- one concern I have about using a transistor design
rather than a relay/capacitor design is that it's not clear to me how
much current is supposed to pass through the cuvette. Other designs
I've seen involve a 5uF or 10uF capacitor rated at 5kV, which
translates to a hell of a lot of charge. The instantaneous current
through a capacitor is given by the equation
i = C(dv/dT)
where i = current, C = capacitance, and dv/dT = instantaneous rate of
voltage change.
The papers I've read have talked about a duty cycle of 150ms on /
350ms off. So, assuming that the voltage across the capacitor rises to
2500V during that 350ms, and assuming a 10uF capacitor, that
translates to about 71 mA available to the cuvette. (Definitely not
something to mess with lightly!) What I'm not clear on is whether this
level of current is actually *necessary*. The neon-sign transformer I
have will provide 3kV at 10mA. I'm not certain whether the available
current is actually enough to do anything to the bacteria.
All that said, though, I suspect that the high capacitance is intended
to provide a relatively long time constant, since the ideal waveform
for this sort of thing is a square wave (which I'm addressing by doing
it in digital logic). I'll go back through the papers I've read and
work out the math on that.
That said -- if anyone happens to know what sort of current is needed,
I'd appreciate your input!
--mlp
Meredith L. Patterson
<clon...@gmail.com> wrote:
> So, assuming that the voltage across the capacitor rises to
> 2500V during that 350ms, and assuming a 10uF capacitor, that
> translates to about 71 mA available to the cuvette.
I should have emphasized "about" more strongly here -- the rate of
change in voltage in a charging or discharging capacitor is not linear
at all. Particularly during the early part of the charge/discharge,
the rate of change will be quite high and thus the current will be
higher as well. It largely depends on what the time constant of the
circuit is. Over a single charging time constant, the rate of change
in voltage is steep, but the second derivative is shallow; over
several time constants, the rate of change drops off a bit.
http://www.tpub.com/neets/book2/3d.htm for pretty graphs.
--mlp
Meredith L. Patterson
current *out of* the capacitor, so it's the voltage drop during the
first discharge time constant that matters most with respect to how
much current the bacteria need. Gah. Death before dishonour; nothing
before coffee.
Anyone here got an IEEE Explore account?
http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=1189489 would
be useful. I can get it at Berkeley, but my VPN is lame and doesn't
get me offsite access most of the time.
--mlp
On Sun, Nov 2, 2008 at 1:31 PM, Meredith L. Patterson
Bryan Bishop
<clon...@gmail.com> wrote:
> Anyone here got an IEEE Explore account?
> http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=1189489 would
> be useful. I can get it at Berkeley, but my VPN is lame and doesn't
> get me offsite access most of the time.
- Bryan
JonathanCline
The schematic in the doc below shows current limiting resistors rated
for 25W
and states the current draw is < 2 mA in each case
(supposedly built for e.coli)
A homemade electroporation device designed with safety in mind
http://www.biosci.missouri.edu/smithgp/PhageDisplayWebsite/PhageDisplayWebsiteIndex.html
George P. Smith SMITH LAB HOMEPAGE
Division of Biological Sciences Tucker Hall
University of Missouri
Columbia, MO 65211-7400
It would be interesting to see other schematics.
On Nov 3, 5:10 am, "Meredith L. Patterson" <clonea...@gmail.com>
wrote: