clinical trial technology

Drug testing could drastically accelerate with ‘Body-on-Chip’ technology

Researchers at KTH Royal Institute of Technology, Karolinska Institutet, and Harvard University have developed a multiple organ-on-chip platform that could drastically accelerate drug testing. Nature Biomedical Engineering described the technology as a provider of accurate predictions of drug effects before the clinical trial.

The body-on-a-chip device simulates eight organs of the human body. An “interrogator” instrument enables the device to mimic normal human blood flow between the organs of the body. It can culture at a maximum of 10 different organ chips and sequentially transfer fluids between their endothelium-lined vascular channels.

Co-lead authors Anna Herland and Richard Novak reported the advance in two articles. Herland is an engineered in-vitro system researcher at KTH and Karolinska Institutet while Richard Novak is a senior staff engineer at Harvard’s Wyss Institute for Biologically Inspired Engineering.

A Clear Flexible Polymer

Organ chips are microfluidic culture devices made of a clear, flexible polymer that’s the same size as a computer memory stick. The polymer contains two parallel hollow channels that are separated by a porous membrane. Cultured on one side of the membrane in one channel are the organ-specific cells. Vascular endothelial cells recapitulate a blood vessel line in the other channel. Independently perfused in each channel are medium specific to cell types of individual organs. The porous membrane enables the two compartments to communicate with each other and to exchange molecules such as cytokines, growth factors and drugs, and drug breakdown products generated through organ-specific metabolic activities.

human vital organs

The team developed a computational scaling method in translating data, which is obtained from drug experiments involving three types of fluidically-linked organ chips to the respective organ dimensions in the real human body to predict changes in drug levels over time and organ-specific toxicity. The approach allows accurate predictions of changes in drug levels overtime for the first time as well as organ-specific toxicities that have been previously measured in humans.

Minimize the need for animal testing

Clinical trials that test new drugs for their safety and efficacy in humans continue to experience high failure rates. Current estimates say only 13.8 percent of all tested drugs show ultimate clinical success and got the U.S. Food and Drug Administration (FDA) approval. The new technology aims to overcome major pain-points in the challenging and costly process of drug development. It is also expected to reduce the need for laboratory testing on animals.

Cancer drug

Herland says the researchers looked into the exchange of lifelike blood and drugs between individual organs, while also giving a way to carry out blood sampling that would mimic blood drawing from a peripheral vein. They also studied the pharmacological effects of cisplatin, a chemotherapeutic drug widely used in cancer treatments, which is administered intravenously and displays unacceptable toxicity in the bone marrow and kidney.

body on chip technology for human drug testing for
Illustration of the human gut chip, liver chip, and kidney chip whose vascular channels are linked via a central arterio-venous (AV) fluid mixing reservoir, and whose organ-specific channels are independently perfused. Image credit: Wyss Institute at Harvard University.

 

She says the analysis nearly reproduced the cisplatin pharmacodynamics effects in patients, including a decreased number of different blood cell types and increased markets of kidney injury.

Herland says quantitative information on how cisplatin is metabolized and cleared by the liver and kidney is produced by the in vitro-to-in vivo translation capabilities of the system. The result makes it possible for more refined predictions of drug absorption, distribution, metabolism, excretion, and toxicity, according to Herland.

amp dac hifi

iFi Zen DAC comprehensive review

If you’re planning to get into hi-fi, one of the first things you’ll need to buy is a headphone amp and digital-to-analog converter (DAC) because audiophile headphones can be challenging to drive, needing more power than your phone or laptop can supply. A good headphone amp and a good DAC will drastically improve the sound quality of your connected device, whether it’s your phone, PC, laptop or even TV.

You don’t need to shell out much money to experience hi-fi sound on your first headphone setup. The iFi Zen DAC is the perfect starting point, which is a DAC and amp combo with enough power to drive power-hungry headphones while working with sensitive in-ear monitors, making the product extremely versatile. iFi Zen DAC offers more features than anybody would think at its price point. It supports for MQA, DSD256, PCM384, DXD384 with balanced inputs, and outputs. You can bypass the amp if you want to use it solely as a DAC. Starting in the hi-fi hobby may not need all of these features, but it’s a good future-proofing as you mature during your audio enthusiasm.

If you only look at the specs on paper, you would think the iFi Zen DAC to cost at least $500, but it only retails for $129, making it one of the best audio bargains on the market today. The iFi Zen DAC is perfect for users who either just dabbling in headphone audio or wanting a portable DAC/amp to take on the go.

Design

The iFi Zen DAC is entirely a metal in a trapezoidal layout. It looks like it can stand up to the abuse of being tossed into a backpack repeatedly as it is built like a tank. The unit may not be the most compact DAC/amp but it is undoubtedly still portable, measuring 117mm long, 100mm wide, and 30mm tall.

A beautiful, smooth-operating volume knob is located on the front of the unit.  The volume knob is backlighted with multiple color LEDs, depending on the sampling rate of the played file. It’s an awesome visual indicator without needing a screen. Also present are the buttons for Power Match (gain), TrueBass (bass boost), a 6.35mm single-ended output, and a 4.4mm balanced output.

digital to analog converter

At the back are a 4.4mm balanced input, variable and fixed options’ switch, single-ended RCA outputs, USB-A port and a DC 5V input for the optional power supply. The unit runs off of USB power only out of the box and if you want to help improve the sound, you need to purchase a wall-wart power supply. While the headphones sound good without the use of a wall-wart power supply, it’s a bit disappointing that it is not included out of the box.

One important thing to note is that no power switch to turn on or off the iFi Zen DAC. The unit powers up as soon as it is connected to a PC and remains on. The volume LED will always stay on, even if the computer is turned off, which is a bit annoying if you’re in your bedroom with the unit.

Performance

The unit handles all digital platforms from steaming to DSD256 to PCM without issue. The iFi’s driver and the control panel is needed on Windows but no need on Macs.

The sound from the unit is excellent, giving sufficient power for power-hungry headphones like the Beyerdynamic DT1990 Pro and Sennheiser HD600. The DAC/amp is also good with low impedance headphones, such as Grado’s RS2i and different in-ear monitors. The unit supports headphones up to 300 ohms, providing enough volume without issues.

When it comes to tonal balance, the Zen DAC is neutral most of the time with a little warmth that helps tame the harsh highs of the headphones like the DT1990 Pro. While bass response is a bit insufficient, dynamics are generally good. Fortunately, the TrueBass option can add some mid to low-end punch without intruding on the mids. TrueBass comes handy when hopping between different genres of music.

The optional iFi power supply is worth purchasing to squeeze out a few extra drops of audio performance. There’s slightly more detail with the optional power supply at high volumes, though playing via USB still sounds excellent.

Conclusion

The iFi Zen DAC is a superb DAC and amp for the price. The unit has features that are rare for entry-level audio products. The Zen DAC has support for most major hi-fi audio formats and it has balanced connections. It elevates the music listening experience of someone new to hi-fi hobby.