Blue-Ray Biotech Support-Technology

Technical Article

  • Choose a Benchtop Microcentrifuge with Safety Considerations

Centrifuge is a piece of equipment widely used in biological laboratories that applies centrifugal force and sedimentation principles to filtrate or separate substances for experimental purposes such as DNA and RNA purification, protein extraction or bio-molecules separation. However, this lab helper can become quite dangerous if not properly used or maintained or if the product is not well-designed with safety considerations for users.

A common danger seen in labs is that lab researchers get hurt when they open the lid of a benchtop centrifuge and the lid drops immediately on their hands or fingers.

A swollen and red finger is not the worst thing when it comes to centrifuge hazards inflicted upon researchers, considering that the operation of centrifuge often involves high-speed spinning enabled by rotor, high temperatures generated by the motor and hazardous (infectious/radioactive/chemical) materials contained in the tubes.

More miserable outcomes might happen when the centrifuge rotors and tubes are not well-seated and balanced, and the lid is not put on securely, or a researcher accidentally opens the lid during operation or before the run is completely stopped, which might result in flyaways of the rotors and tubes driven by centrifugal force. The metal rotors, sharp-edged debris, hazardous materials and aerosols could bring casualties.

Less dangerous but still harmful and annoying is the noise created by high-speed operation during a centrifuge run if the centrifuge is not designed and manufactured with noise-reduction considerations.

Choose a Centrifuge with Safety Designs to Avoid Lab Dangers

Therefore, when deciding on the purchase of a centrifuge, the users, in addition to considering on the types of machines that will meet the lab purposes and associated requirements for functions, capacity and speed, they should also take safety designs of the products into account.

Addressing the afore-said pain-points of users discovered in market investigations and researches, some centrifuge manufacturers have tried to add designs to their products to make it safer for users during operations.

For example, Blue-Ray Biotech, a company whose centrifuge products focus on the category of high speed benchtop microcentrifuge, has a number of innovative designs addressing user’s safety and convenience.

Lid Drop Protection and Motorized Dual Lock

Their flagship centrifuge TurboFuge (24-place capacity/21,400 x g max. RCF/15,000 rpm max. speed), which has been added with Lid Drop Protection which will hold the lid at 5 - 60 ° during openness to allow easy loading and unloading of tubes and avoid accidental lid drops and injuries (Figure 1).

Figure 1. Lid Drop Protection allows easy loading and unloading of tubes and avoid accidental lid drops and injuries.

Secondly, Motorized Dual Lock is applied to the lid instead of the conventional solenoid lock design, so that the lid will be safely locked during centrifugation operation to eliminate the chance of leaks, spills and flyaways and their deadly results (Figure 2).

Figure 2. Motorized Dual Lock ensures the safety in operation.

Imbalance Detection

Loads imbalance is often cited as one of the main reason for rotor flyaways, so the TurboFuge manufacturer has added a Rotor Imbalance Sensor beneath the chamber and near the motor, so that the centrifuge will be automatically turned off once imbalance is detected  (Figure 3)  and the user will be immediately notified to adjust the loads. The innovative intelligent design is extremely useful to eliminate imbalances potentially caused by user errors in their loading practices.

Figure 3. Imbalance Sensor turns the centrifuge off immediately if rotor imbalance is detected

Aerosol-Tight Rotor Cover and Robust Metallic Chamber

The potential dangers associated with centrifugation are not limited in direct contact with hazardous materials; the exposure to chemical or bio-hazardous aerosols is lethal alike. Therefore, the innovative Aerosol Tight Rotor Cover can be chosen for the rotor (Figure 4), so that even when leaks and spills occur inside the chamber, the researchers will be protected from the dispersal of hazardous aerosols.

Last but not least, the interior of the chamber, or the bucket, is constructed with metal material which will reduce noise, facilitate heat dissipation and provide solid protection against flying metal rotor (Figure 4).

Figure 4. Aerosol-Tight Rotor Cover and Robust Metallic Chamber.

Autoclavability and Robust Ventilation Provides Protection to Samples

The protection of samples is also important for ensuring the success of centrifugation and the quality of experimental results. The TurboFuge is also made with sample protection designs.

First, the metal lid and rotor of the TurboFuge are made autoclavable so that they can be detached and treated in an autoclave for pressurized and heated sterilization to avoid contamination of centrifugation samples.

Secondly, enhanced ventilation design (Figure 5) is applied to reduce the temperature created during high-speed rotation, so that even when the TurboFuge is run at its maximum speed of 15,000 rpm for as long as an hour, the interior temperature of the instrument will not exceed 40° C and will not affect temperature-sensitive samples.

Figure 5. The Robust Ventilation Design prevents heat accumulation at high speed to protect sensitive samples.

These design highlights have reflected the market trend that biotechnology equipment manufacturers, while making every bit of effort to improve the functions and performance of their products to satisfy customer needs, have put more emphases on user’s convenience, health and safety as selling points of their products.

  • IoT-enabled Remote Monitoring of PCR Thermal Cyclers

The inception of the IoT era

The world has entered the era of the Internet of Things (IoT), where many devices (things) can be connected to the Internet/Intranet for data exchange and application. Many industries have shown interest in the new technology and are finding out what values it can create. The manufacturing industry has taken the lead in this new trend, where the applications of IoT are expected to usher in a “paradigm shift” in so-called “Industry 4.0” production. Significant changes are also taking place in molecular biology laboratory equipment. Several of the main players in the field have started to introduce remote monitoring and other IoT-based features into their products to increase convenience and efficiency as well as precision and accuracy.

Laboratory equipment turning a new page with new technology

The PCR thermal cycler is an instrument now widely deployed in biochemical and medical laboratories for the amplification of DNA segments or sequences for such purposes as medical/biological studies and research, the detection of pathogens, paternity testing and even criminal investigation. A mixture of DNA primer, thermo-stable enzyme and nucleotides is subjected to a cycle of heating and cooling to make many copies of a specific region of DNA from an initial small sample of biological material. The quality of the results depends largely on precise control of the temperature and time of each reaction cycle. The whole process for each PCR procedure usually takes 30-40 minutes but can run for up to 2 hours.

The entire process is automatic and controlled by the instrument itself. Most often the technician just sits by the machine waiting for the results, intervening only in the event an error message should be displayed. What if the technician could be elsewhere and view the whole process remotely, and receive error alerts and status notifications automatically on a Smartphone or other mobile device? Nowadays IoT-based remote technology is providing such solutions.

PCR thermal cyclers can be remotely monitored now

Blue-Ray Biotech is one of several molecular biology laboratory equipment manufacturers that has already introduced IoT technology. The PCR TurboCycler of Blue-Ray Biotech has a built-in WiFi module that allows the PCR process to be monitored remotely. The information that appears on the machines own screen, such as temperature and time, can now also be seen on the screen of a Smartphone in real time. A mobile application called TurboAPP allows users to install and configure the dashboard. The WiFi module built into the machine serves the same function as a wireless router and a connection can be established directly with a Smartphone. This makes monitoring possible in a laboratory where there is no other WiFi AP or Router deployment.

TurboApp WiFi connections make it possible for the operators of PCR machines to do other things rather than sit around waiting for the cycle to complete. Monitoring of the progress of the PCR cycle and operating status of the machine can be done on a Smartphone or other device from elsewhere in the laboratory. Any alerts or alarms will be transmitted to the Smartphone and the operator will be informed when the process has been completed.

No more waiting around

The Wifi module built into the TurboCycler has a direct range of up to 10 meters. However, if the laboratory building has wireless access points or routers, the range of data transmission can be much greater and operators are often able to move freely within a much larger area and still receive the signal from their PCR machines.

In addition to monitoring the process of a specific PCR machine, the app also allows users to check the availability of PCR machines in the laboratory, so that they can see if it is possible for them to slot in a booking.

In addition to remote monitoring of the PCR thermal cyclers, Blue-Ray Biotech is also working on the inclusion of remote monitoring to their upcoming new range of centrifuges.

More features can be expected to come with IoT technology

This is just the beginning. More laboratory equipment that uses IoT-based technologies can be expected. Many fantastic features can be included with IoT. It can make equipment “smarter”, more efficient and more convenient.

For example, a system can be designed that gathers operating data from machines and uploads it to a database in the cloud in real time. This large accumulated data pool can then be used to train machine-learning models for the implementation of preventive maintenance of the monitored equipment. Remote diagnosis and trouble-shooting routines can also be included to prevent unexpected shutdowns and avoid damage and loss.  

It might sound fanciful, but it is not fiction. Related technologies are already in place in areas like factory automation and aftermarket maintenance services such as those for elevators and air conditioners. However, we have to consider many factors when deciding on the features to be adopted, including the practical needs of users and the appropriate cost structure of products. The main principle for consideration is the maximization of the overall benefit our products can deliver to users at a reasonable and effective price.

  • Unique Temperature per Cycle Control Algorithm for Friendly CRISPR Assay Setting

Unique Temperature per Cycle Control Algorithm  for Friendly CRISPR Assay Setting

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-related genome editing technology has become the most eye-catching life science innovation in the past few years. With these systems, researchers can permanently modify genes in living cells and organisms and, in the future, make it possible to correct mutations at precise locations in the human genome in order to treat genetic diseases.

Throughout the process of a CRISPR system assay and downstream genome editing detection, precise reaction temperature control is a crucial element for the successful outcome. Not only should the steady reaction temperature be accurately maintained, but the cooling rate in some steps should also be controlled. For example, the temperature of a reaction mixture is requested to be heated to 95°C and then cooled to 85°C at a ramp rate of 1°C/sec, then slowly cooled down to room temperature at a ramp rate of 0.3°C/sec. Utilizing a thermal cycler, a so-called PCR machine, to perform the assay temperature control would be a good idea.

Thermal cyclers are designed to heat or cool the reaction mixture to a certain temperature and hold the temperature steadily for certain periods of time. This makes them the ideal instrument to perform temperature control for assays that need to be carefully taken care of. Some thermal cyclers can be adjusted to heat or cool at a slower ramp rate to accommodate the needs of the tasks mentioned above. However, due to the fact that the heating or cooling is not taking place at a constant rate (see Figure 1), it is not easy to precisely define the ramp rate needed for the task. 

Take the task for cooling from 85°C to room temperature at a ramp rate of 0.3°C/sec as an example. By adjusting the ramping rate to 0.3°/sec, you can simply set up an 85°C step, followed by a 25°C step and let it run. The cooling rate of your reaction mix may be more than 0.3°C/sec at the beginning and less than 0.3°C/sec at the end. The other way to control slow ramping is by changing the temperature setting for a certain step after each cycle. In this way, you can achieve precise time and temperature control throughout the entire duration, but the programming process may be a bit more complicated. You' ll need to configure a program containing two or more temperature steps (so that you can repeat or cycle them) and change their temperature setting after each repeat (cycle). Let’s use the example mentioned above again. With an 85°C reaction mixture, you need to set an 84.7°C, 2 sec step and an 84.1°C, 2 sec step and set a -1.2°C/cycle temperature decrement, then repeat these two steps for 50 times. In this way, you’ll get precisely -0.6°C cooling every 2 sec. If you want to have smoother temperature change, you can even set an 84.7°C, 1 sec step and an 84.4°C, 1 sec step, a -0.6°C/cycle temperature decrement, then repeat these two steps for 100 times. Most cyclers have a cycle number limit, so you may need to add more temperature steps and reduce the cycle numbers (see Table 1). You need to consider the number of steps, the temperature difference between each adjacent step, the per cycle temperature decrement setting and cycle numbers.

Table 1

Repeat

Temperature

Hold Time

100 cycles,
-0.6°C/cycle

84.7°C

1 sec

84.4°C

1 sec

Repeat

Temperature

Hold Time

50 cycles,
-1.2°C/cycle

84.7°C

1 sec

84.4°C

1 sec

84.1°C

1 sec

83.8°C

1 sec

The new TurboCycler Lite thermal cycler from Blue-Ray Biotech provides a new option for slow ramp control. By allowing to repeat a single temperature step, you just need to set the per cycle temperature decrement to meet the cooling rate requirement and repeat this step until you get the final temperature. If the cycle number needed exceeds the cycle number limit (99 cycles for TurboCycler Lite), just add another set of repeat (see Table 2).

Table 2

Repeat

Temperature

Hold time

99 cycles, -0.3°C/cycle

84.7°C

1 sec

99 cycles, -0.3°C/cycle

55°C

1 sec

2 cycles, -0.3°C/cycle

25.3°C

1 sec

The advanced slow ramp control makes the TurboCycler Lite an ideal instrument for CRISPR-related assays. It's also equipped with a full temperature range lid heater which can be beneficial for use as an incubator for NGS sample pretreatment and other experiments.

Quickly-evolving biotechnology developments simplify and speed-up researchers’ work on exploring the truth of nature. As a member of the life science community, Blue-Ray Biotech promises to develop the most innovative laboratory instruments and provide the best service to support scientists to fulfill their dream.