Manufacturing Bits: Sept. 30

Muscle-on-a-chip
Harvard University has developed a human airway muscle-on-a-chip as a means to test new drugs for the treatment of asthma.

There is an urgent need for a new breakthrough in this arena. The majority of drugs used to treat asthma have not changed in 50 years, according to researchers at Harvard. Asthma affects nearly 25 million people in the United States alone.

Asthma, according to Harvard, is a patient-specific disease. And the animal models traditionally used to test new drugs often fail to mimic human responses.

Hoping to overcome these roadblocks, Harvard’s muscle-on-a-chip technology mimics the way muscle contracts in the human airway during an asthmatic episode. The muscle-on-a-chip consists of a soft polymer that is mounted on a glass substrate.

Researchers mimicked an asthmatic airway on their airway muscle-on-a-chip by first introducing Interleukin-13 (IL-13), a natural protein often found in the airway of asthmatic patients. Then they used a neurotransmitter called acetylcholine to trigger the smooth muscle to hypercontract, and a bronchodilator used in inhalers called a β-agonist to elicit muscle relaxation. (Source: Harvard)

To mimic asthma, interleukin-13 (IL-13) was inserted onto the chip. (IL-13) is a natural protein found in the airway of asthmatic patients. Acetylcholine, a neurotransmitter that causes smooth muscle to contract, was added to the mix.

As a result, the airway muscle on the chip hypercontracted. Researchers also triggered the muscle to relax using drugs called β-agonists. “Asthma is one of the top reasons for trips to the emergency room–particularly for children, and a large segment of the asthmatic population doesn’t respond to currently available treatments,” said Wyss Institute Founding Director Don Ingber on the organization’s Web site. “The airway muscle-on-a-chip provides an important and exciting new tool for discovering new therapeutic agents.”

pH image sensor
The Toyohashi University of Technology has developed medical diagnostic biosensing system for analyzing blood and urine for the early diagnosis of diabetes and Alzheimer’s disease.

The new biosensing technology has detected amiloid beta-peptide, an agent responsible for Alzheimer’s disease. The system is based on a semiconductor image sensor charge coupled device (CCD). The image sensor consists of 128 × 128 pixels, which is sensitive to small changes in an electric field.

Toyohashi’s semiconductor image sensor (Source: Toyohashi)

The 128 × 128 pixel-type potassium ion-sensitive image sensor is composed of a CCD-type pH image sensor. It also consists of a PVC-based plasticized membrane containing valinomycin, a potassium ion-sensitive ionophore. The potential slope was 50 mV/decade for a potassium ion concentration between 10−3 and 10−1 M.

Multiple diseases can also be simultaneously diagnosed. This is done by placing different antibodies on different sensing pixels out of a total of 16,384 pixels, according to researchers.

Contracting a disease leads to expression of proteins specific to the disease, according to researchers. This biosensing system makes use of the specific protein as the antigen and a marker that captures the protein as the antibody.

Traditional methods use fluorescent probes and microscopic cameras, but this process is time consuming, according to researchers. “With this technology, an antigen-antibody reaction is used as in conventional methods, but fluorescence is not measured. Instead, this method employs a semiconductor image sensor to detect minute changes in electric potential generated during an antigen-antibody reaction,” according to researchers at the Toyohashi University of Technology

Artificial immune system
The Scripps Research Institute (TSRI) has been awarded $7.9 million from the Defense Advanced Research Projects Agency (DARPA) of the U.S. Department of Defense (DoD). With the funding, researchers will develop an artificial immune system.

The artificial immune system will consist of libraries of different molecules. They will enable individual compounds, which, in turn, will detect or neutralize an array of biological and chemical threats.

One group in the program will develop libraries of functional compounds. The libraries will contain molecules each tagged with a DNA “barcode” that identifies the molecules’ chemical structure. The group will continue to develop TSRI’s microfluidic circuit, which screens single compounds suspended on artificial beads. The microfluidic circuit can process more than 200,000 compounds in a matter of hours.

Another group in the program will develop variants of oligonucleotides, which are short, single-stranded DNA or RNA molecules. Researchers will leverage a system known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to evolve novel function molecules.

Implementation of the technology will be tested for diseases such as diabetes, Alzheimer’s and Parkinson’s.