Shrinking the Lab is not so Dinky

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Lab-on-a-chip Device

When feeling under the weather, we commonly end up sitting in a doctor’s office chair. Blood and saliva samples are whisked away to a room filled with instruments, some as big as a washing machine. In this room technicians run a litany of tests that can take hours or days for results to come through.

These medical laboratories and the tests they provide have evolved from pregnancy testing in ancient Egypt that measured urine’s ability to germinate seeds to the now ubiquitous blood workup at a yearly physical exam. For patients, getting tests done at a doctors office hasn’t changed drastically in the last few decades, but there’s an evolution occurring where these tests and instruments are getting miniaturized.

This growing field of shrinking laboratory instruments is called “lab on a chip” technology. When people say chip, it means many of these technologies are built handheld pieces of glass, plastic, or even paper. By shrinking computers, digital computing technology revolutionized our world, fitting into places previously unheard of such as cars, ovens, and phones. When it comes to shrinking a lab instrument, the benefits take a different shape.

Paper based Lab Tests and Tools

At first thought, using paper to perform medical tests seems rudimentary compared to the whirring computers in a high tech hospital lab. By removing electricity and the expensive complex components, paper-based tests are more affordable and highly mobile. Paper-based tests are often more rugged and compact, which makes their transport and use outside of the hospital plausible. In fact, a paper lab test can be bought in corner pharmacies today.

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Sandwich Immunoassay

The at home pregnancy test is an example of a paper based test. Many of these tests measure the amount of a hormone, human chorionic gonadotropin (hCG), in urine. This hormone is only present in urine when the patient is pregnant. These tests function by using the paper to wick the urine across several key regions that facilitate the measurement of hCG. First, the paper moves the urine across hCG antibodies, molecules that will only attach to hCG, with tiny colored beads attached. The antibodies that captured hCG are then carried over a second bed of antibodies attached to the paper. This creates a “sandwich” with paper acting as the plate, antibodies as the bread, a filling of hCG, and a colored bead garnish. The sandwich shows up as a thin line of color only if the urine holds hCG confirming the user is pregnant.

Researchers at the University of Washington are expanding the use of paper for diagnostics by developing a test for malaria. Similar to the pregnancy test, this device uses lateral flow to move sample around, but a key difference is this study uses dissolvable sugar to delay the delivery of certain samples. These delays are necessary for measuring malaria; in the pregnancy test only one reaction step occurs, but the researchers are using malaria as an example of an application that requires multiple steps to make a measurement. In this multi-step device, all the samples are delivered at different times automatically because the researchers are able to control how long it takes the sugar to dissolve. Controlling how fluids move on paper automatically enables increasingly complex tests to be run without adding any mechanical components.

Human on a Chip

Where paper devices have shown their use in relation to diagnosis, there are other scientists trying to make chips that mimic human organs. In the future this sort of device could allow doctors to test which drugs would be easily absorbed in a patient’s intestine by using a chip that has their own gut cells. By performing these tests on a patient’s actual cells, doctors can avoid prescribing drugs that are ineffective or even harmful to a patient .

Researchers at the University of North Carolina at Chapel Hill gathered intestinal cells during gastric bypass surgery, with the patient’s consent, to make an intestine chip with the patient’s’ own cells. To grow the cells in the lab, researchers add growth factors, chemicals that tell cells how to grow correctly, and give the cells a carefully tuned surface to grow on. In the laboratory setting, hard plastics are often used to cultivate cells, but this is not a natural environment for cells, which are used to being surrounded by a soft support infrastructure inside the body. In this work researchers made a soft mold that mimics the shape of the intestine and provides a more natural surface for the cells to grow on. Using this technique the researchers were then able to make a chip that not only looks, but also and acts like our intestines.

With devices like this intestine on a chip starting to appear, there is hope for changes in the way drugs and other therapeutics can be developed. For example, much of drug efficacy testing occurs in mice. Although mice are mammals, which makes them similar to humans in some ways, they are also very different from humans. Frequently drugs that look propitious in mice turn into let downs when tested in human clinical trials. Therefore, by testing drugs on actual human cells early in the development stage mouse lives are spared and the initial investigations are more representative of the final use in humans.

An Imagined Future on a Chip

With “on a chip” technology, the way we approach medicine may look very different to the medicine of today. Waking up at home feeling under the weather, you may go into your medicine cabinet and grab your home diagnosis kit. You swab your cheek with a q-tip and insert the end into a credit card sized chip, you press a button allowing the fluids to flow through the chip and after 5 minutes you have your diagnosis- it’s strep throat.

You message your pharmacy, take a picture of your test results, and receive a notification that your medicine will be ready in a half hour. The medicine you receive was developed through organ on a chip testing and no laboratory animals were used during any stage. Going to the doctor’s office for something as routine as strep is practically unheard of. With the work going into chip technologies, this imagined future may soon become our reality.

Peer edited by: Elise Hickman and Matthew Varga.

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A Blood Test to Diagnose Autism Spectrum Disorder

When it comes to diagnosing children with autism spectrum disorder (ASD), earlier is better. The American Academy of Pediatrics recommends screening children for ASD between 1.5 – 2 years of age. However up until now, diagnosis of ASD has been driven by clinical observations, often behaviors not yet formed in children this young, and consequently most children are diagnosed around 4 or 5 years.

Earlier diagnosis allows for specialized interventions that capitalize on the plasticity of toddler’s brains while implementing proven behavioral therapies like applied behavioral analysis and developmental relationship-based approaches to promote communication and social interaction.

One of the challenges in diagnosing ASD is the variability in symptoms along the spectrum, and the change in developmental standards with age. Some symptoms common to ASD are common to other disorders as well and therefore do not aid in diagnosis. With 1 in 59 children identified with ASD and median diagnosis age ranging from 3 to 5 years, research in the field has been two-pronged: characterizing the variability in the disorder and improving diagnostic tests.

Depiction of ASD aspects at each part of the spectrum courtesy of Rebecca Burgess

Depiction of ASD aspects at each part of the spectrum (image courtesy of Rebecca Burgess).

A blood test to diagnose ASD has been nothing but a pipe dream…until now. Last month, the first blood test for autism was confirmed as highly accurate in a secondary trial. Blood tests for other diseases often test for a single marker, such as carcinoembryonic antigen for colon, lung, and liver cancer, or TRU-QUANT (CA27.29) for breast cancer. Efforts to identify a single metabolic marker for ASD has fallen short. So what was the reason for success in this new endeavor? Instead of exploring for a single metabolite that predicts ASD diagnosis, researchers from the Rensselaer Polytechnic Institute (RPI) utilized big data methods to find patterns in metabolites involved in metabolic pathways implicated in ASD physiology. Both pathways have been implicated in ASD physiology, and by using information on 24 metabolites instead of just one, the predictive algorithm had 88% accuracy rate when applied to a new data set. The RPI lab, led by Juergen Hahn, is not an autism-focused lab. Instead, the Hahn research group focuses on new techniques for systems engineering and analysis and the application of those analyses to biochemical systems – like the methionine and transsulfuration pathways for ASD. Unlike behavioral symptoms that do not emerge until later in development, a blood test can be administered at younger ages allowing for earlier diagnosis and intervention.

There are several things to consider moving forward with a diagnostic test for ASD, including:

  1. Will the algorithm be validated in additional data sets?
  2. Are the metabolites readily measured in ASD diagnostic settings?
  3. Does the algorithm perform similarly across the autism spectrum?

Will this test change the face of ASD diagnosis and treatment – what do you think?

Note: This article refers to the autism spectrum as “Autism Spectrum Disorder (ASD)” parallel with current research areas. However, many involved in autism spectrum advocacy and collaboration argue to drop the term “disorder” as well as labels such as “high functioning” and “low functioning”. You can learn more here from the Art of Autism.

Peer edited by Rachel Haake.

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