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Human Practices

Social and scientific context:

Doing science is a captivating, exciting and rewarding activity, but has its drawbacks too. Science requires efforts that can be consuming and very costly. Passion for science often overcomes these problems but our team thinks it would be better if these hurdles could be lightened, and that it is possible to do!

Labware, consumables, reagents, instruments, most of the things we are commonly using in a lab cost a lot of money to the scientists who absolutely needs them to perform their experiments. The instruments are often one of the major expenses in science and can cost up to hundreds of thousands dollars for a single unit. Scientists must get significant funding to be able to get their hands on these instruments, leading to results that can be published in papers that in turn facilitate access to more funding. The problem with the cost of the instruments doesn’t stop at the acquisition; the running cost of many machines can be incredibly high because many of them must use specific proprietary consumables (like pipette tips and containers) that can cost up to 10 times the price of the usual equivalent consumable we use in the lab.

The high price of the instruments in science can be addressed in several ways. First, scientist can join together to split the bill. The problem with this is that even by sharing the cost between colleagues, the price for big instruments like a good liquid handler can still cost each participant more than a hundred thousand dollars. Second, scientist can team up to write a grant, giving them more chance to receive the funding for what they need, but there is still always a big chance the grant will not be accepted. Even if one of these workarounds allow you to obtain the machine you want, they do not necessarily overcome the high running cost of many instruments. Also, buying an instrument in group can lead to management problems if many people from different labs needs it at the same time or if divergence emerges in how to maintain the instrument.

Another way to get access to an instrument at a lower cost is to build it by yourself from scratch (DIY: Do It Yourself!), which sometime demand skills we don’t have access to (electronic, software, mechanic, optic) and the process of building an instrument can be really time consuming.

We begin to see more and more open source projects for different laboratory instruments. For examples: OpenFuge, an open source centrifuge, OpenPCR, an open source thermal cycler and OpenTrons, an open source liquid handler. Because they are open source, these projects offer to the community all the documentation they need to build these instruments themselves saving all the conception time. It also allows people to improve the design or modify it at their convenience without starting from scratch. If you don’t have the skills or the time to build it yourself, you can usually buy these instruments for a really low cost compared to the proprietary one.

Another common problem in science concerns the amount of time spent in the lab and how we spend it. Each of our experiments must be planned, designed, performed and analyzed carefully. Many experiments can be repetitive and boring: students, technicians and scientists would certainly increase their productivity by spending their time designing new experiments or analyzing their data. Other experiments can take quite a while to do, way over a normal working day and when dealing with living organisms, you must sometimes do your experiments when your organism of choice is ready and this can be when you would normally be sleeping or enjoying your well-deserved week-end!

To solve these problems, liquid handling robots are there for us. These machines can pipette for us, do our PCR, move our labware and heat or cool it and all of this can be done an endless number of time and with a lower error rate. The main goal of these platforms is freeing scientists’ time while doing all the long and repetitive work for us. But as mention earlier, these instruments are expensive and accessible only to some laboratory with high funding. A simple robot only capable of pipetting can easily cost more than 50 000 $ while a more complex robot composed of multiple instruments (centrifuge, plate washer, plate heater, etc.) can easily cost from 150 000$ to more than 500 000$ depending on the components. The running cost of these robots is also quite expensive due to the high price of specific consumables that must be used with them.

Another problem with most of these robotic platforms is the lack of flexibility. This is particularly true for those coming at a lower price point that can only do pipetting. Most experiments require different modules or instruments to get done properly. We need to heat our tube for enzymatic reaction or to grow our culture; we need magnets to do nucleic acid purification on magnetic beads; we need to measure the optical density of our culture medium to know if our cell culture is ready; we need a gel box to separate our DNA and a camera to take pictures of the gel. Those are only some examples of instruments that a robot would need if we wanted it to do what we do everyday in a biology laboratory. Getting all the modules needed to cover almost all the experiments done every day in a lab would cost a fortune, and many are in fact not even available from robotic companies. Interfacing your existing hardware with a robot is also not usually possible or can sometime lead to high cost so the robot manufacturer could write the proper driver for you.

Many liquid handling robots are built for high-throughput experiments and are useful only if you have a huge number of samples to process. Therefore, most of the modules available from robot manufacturer are built to work only with multiwell plate. The reality is that most laboratories, mainly in academic, don’t or barely perform high-throughput experiments. Working in multiwell plate is not always the best way to work for them, but tedious and repetitive protocols still need to be performed manually.

The softwares available are also often a problem. Many softwares used to control robots are complicated and not flexible enough. A dedicated specialist must be trained to develop protocols and run the robot, limiting a more widespread use for scientists in general. In other cases, the operations required by users are simply not implemented in the software, and as most of these softwares are close source and cannot be modified, there is often no way to perform them. Many users are also facing unresolved bugs and cannot upgrade their software and get access to new functionality unless they spent money for the new versions.

With all these points in mind, our team designed what we thought could be an answer to these issues while keeping the positive aspects of using robots in the lab. We wanted to build a complete platform that:

1. is affordable for most laboratories
2. is inexpensive to run on a daily basis
3. offers a large selection of modules so it can perform experiments performed every day in a lab and therefore free more time for people who must perform these experiments
4. could be built or modified by users if they want and create or add existing hardware for the platform, and
5. has a flexible open source software that people can get and update for free (so they can always have the latest version with all the new functionalities and bug fixes) or modify if some functionality is missing for their applications.

We first look at what was done on the market and in the open source community, but we have not yet found a platform offering all the features and modules we had in mind or the software flexibility we wanted. That’s why we decided to build our own liquid handler from scratch!

The first step to build an affordable hardware was to use, when possible, easy to find components available at an affordable price. For example, many parts of the robots are from OpenBuilds or McMaster-Carr and available to everyone for a decent price.

The second step was to make our robot compatible with labware readily available at low cost. In a single experiment, hundreds or even thousands of pipette tips and many tubes of all sizes can be used. As we run several experiments in a day the cost of these consumables is not negligible and can even quickly come quite high. For many laboratory the cost of the labware must remain as low as possible. We chose regular consumables that are used by scientists.

The third step was to license it completely open source so people could either buy it, build it or modify it if they want to. All the 3D model of every part we had to machine or 3D print is available so they can be reproduced. The 3D models of the whole platform and every module is accessible so people would be able to build them on their own and save on building cost. An open source software available for free also contribute a lot to save money. All these items are provided under the Creative Commons Attribution-ShareAlike 4.0 International license.

Creative Commons Attribution-ShareAlike 4.0 International license

We think these characteristics could assure the low cost of our robotic platform, allow people to get access and to run a liquid handling unit at a much lower cost, and promote the open development of our platform.

A robot that doesn’t cost a fortune is a nice feature, but if this robot cannot do what you usually do in your lab, it will still not be of much help to scientists. We think that having a flexible and modular robot that can run every day experiments is a key feature for an automatized platform dedicated to biology.

Being modular and having many modules that can mimic what we usually do in a lab is the first step toward higher flexibility. We had many ideas of modules (too many in fact!) and we had to prioritize. We decided to first focus on experiments commonly done in synthetic biology so, in addition to the obvious single channel pipette and a gripper, we decided to add a multi-channel pipette to help when more samples must be processed, and to ease the pain of working in multiwell plate by hand when needed. We created a module that can grow a biological culture at a specific temperature while mixing it and reading in real-time its optical density so a user doesn’t have to stop what he/she is doing several times to check on the status of a culture. We also developed two modules, one for 96-well plate and one for the classic 1.5 ml tube, that can heat or cool your samples and apply magnetic field so a user can do an enzymatic reaction and a nucleic acid purification all in the same module without any human intervention. We also decided to add a centrifuge, one of the most used tools in a biology lab. With all these modules together, many popular protocols can be done from start to finish without any user intervention during the experiment. All these modules can also be used individually so if someone only needs a specific module, he doesn’t have to buy a whole platform.

Another important point toward flexibility is carried by the open source licensing (Creative commons Attribution-ShareAlike 4.0 International license). Because the documentation for the hardware and the software is made available to everyone, this opens a world of possibilities. People can add and interface new modules with the platform. Everything, from the platform to the modules and the software can be either improved or adapted to specific applications as long as the modifications are made publicly available using the same conditions. It could even be possible to add already existing third party modules or instruments if a company helps you interfacing them. We think that everyone can benefit from the whole community working on the platform.

At last, even if your robot has a low cost and even if it is the most flexible thing in the universe, nobody will want to use it if the robot is too complicated to use. To overcome that, we are building a software with an easy to use and intuitive graphical user interface. We think that nobody should need any computer knowledge to run their experiments on an automated platform. Our software, while easy to use, is yet really powerful and can control every module we have made and is built to be flexible enough so anyone can had new modules with new capabilities.

With this project, we think the life of many students, technicians and scientists can be easier and more productive. If all the repetitive, long or boring parts of experiments can be done by robots, science could be even more pleasant, captivating and productive. The time of everyone could be spent to think more about important experiments, to design experiment in a better way or to analyze data and think about the results instead of rushing new manipulations to get more data. Time could even be spent sleeping a little more so people would get better ideas, be less error prone and probably enjoying science even more!

Potential savings for specific modules:

We have compared the price of instruments available on the market with some of our open source modules. This exercise helped us to know if what we were building was following our vision of lowering the hardware cost. We decided to compare bench top centrifuges with our own, spectrophotometers with our TAC module (as it can read optical density), and the price of a complete pipette kit with our single and multichannel pipetting modules (because our modules can pipette with tips supported by all of these pipettes). You can see in the tables below that the building cost of our open source modules can be less than 6 times the price of commercially available instruments. It must be noted that because our modules are prototypes, we could not estimate the price of a ready to sell modules so we put the material cost as reference.

Centrifuges:

At a higher price point, these centrifuges can hold more tubes than our centrifuge, but can spin at the same speed as our centrifuge (the centrifugal force has been deliberately limited to 6000 g for now for safety purposes but our motor can go up to 20 000 g). The problem with these bench top centrifuges is that they cannot be used in an automation setup. The Openfuge is a great initiative and have been developed with an even lower cost than our centrifuge but it has the same problems as the commercial centrifuges shown here, it cannot be used easily on an automated platform.

Close-up	Product	Price
	Heraeus Pico	3667 $
	Eppendorf 5418	3013 $
	Sorvall Legend 17	3336 $
	Thermo mySPIN mini 12	755 $
	Openfuge (Open source, material cost)	263 $
	Biobot centrifuge (material cost)	394 $

Prices in Canadian dollars

Spectrophotometer:

We looked at the price of photometers that can hold a standard 25 mm tube so they can be compared on usability criteria. The advantage with the commercial spectrophotometers is that they can read quickly different wavelengths of light in a wide spectrum. But they are built to only read light. Our TAC module can also read any visible wavelength as long as the right LED or optical filter is used in front of the sensor. In addition, our TAC module reads the optical density in real time while mixing and heating the cell culture.

Close-up	Product	Price
	Thermo Scientific Spectronic 200	2837 $
	Genesys 20 visible spectrometer	4122 $
	Biobot TAC (material cost)	441 $

Prices in Canadian dollars

Pipettes:

As our pipette modules can manage all kinds of tips on the same shaft and has a great pipetting precision, we decided to compare the price of a complete set of pipettes versus our single channel or multichannel pipetting modules. Other automated platforms use these pipettes as the base of there pipetting modules (OpenTrons, Andrew) and must use several types of pipette to pipette different volume. The other reason why we compare manual pipette with our automated pipette module is that getting the price of a single pipette unit found on commercially available liquid handler is quite difficult. Like on many liquid handlers, the drawback of our pipetting units is that they can only be used on a robotic platform, but they still are highly precise and comes at a very low material cost.

Single channel pipettes:

Close-up	Product	Price
	Thermo Scientific Spectronic 200 (for p2, p20, p200 and p1000)	943 $ for a kit of p20, p200, p1000 346 $ for a p2 Total of 1289 $
	VWR Single-Channel	943 $ for each pipette (p2, p20, p200 and p1000) Total of 2160 $
	Eppendorf Single-Channel	1496 $ for a kit of four pipettes (p2.5, p20, p200 and p1000)
	Biobot Single channel pipette (material cost)	188 $

Prices in Canadian dollars

Multichannel pipettes:

Close-up	Product	Price
	Eppendorf Research plus Adjustable Multichannel pipettes	Each pipette cost 743 $ 3 pipettes are needed to cover our volume range. Total : 2229 $
	Thermo Finnpipette F1	Each pipette cost 1510 $ 3 pipettes are needed to cover our volume range. Total : 4530 $
	Biobot multichannel pipette (material cost)	846 $

Prices in Canadian dollars

Scale-Up and Deployment:

According to a report of the Markets and Markets consulting firm, the Lab Automation Market currently worth 3.5 billion and is expected to reach 5 billion dollars by 2020. This report also states that the modular automation segment is the larger part of the market due to the affordable cost and reduced space needed. So, by developing a modular platform with one the lowest cost and highest flexibility in the market, it is possible to take a significant part of this market, given the right amount of visibility. The fact that the platform is open-source will increase its spreading through small laboratories around the world.