Introduction

Nidus BioSciences is a spinout of the University of Rochester making “MicroBubble Arrays” (“MBA™s”) for applications in the $18B (2020) “biochips” market as well as other markets that leverage its unique patented (US8,753,880US9,346,197, and US9,457,497) “Gas Expansion Molding” (“GEM™”) manufacturing technology and the MBA™s Nidus makes using the GEM™ process.  Nidus’s technology is based on over $500,000 in non-dilutive grant funding, and targets a number of high-value commercial applications.

Gas Expansion Molding (“GEM™”) Manufacturing

Nidus’s MBA™ technology is based on the discovery by one of our founders, University of Rochester Professor Lisa DeLouise, that semiconductor chip fabrication technology can be used to create tiny bubbles in a polymer when those bubbles are formed over a silicon template with pits in it.

The first illustration shows how this patented GEM™ manufacturing process works.  Briefly, we use sophisticated semiconductor chip fabrication technology to make a silicon template with pits in it — the illustration shows only the template’s top as the horizontal white square, with the cylindrical pits shown in brown.  Then, we pour polymer over the template and place the sandwich in an oven — in this illustration we don’t show the polymer so that we can focus on the air bubbles (red) that rise above the pits and expand into the polymer to create a regular array of microbubble shaped wells, that is, our MicroBubble Array.  We can control the size of the air bubbles and therefore the resulting pits by changing the time and temperature in the oven, the size of the pits (including whether they’re cylindrical or square), and the viscosity of the overlying polymer.  We can also control the spacing of the microbubbles by how we use semiconductor fabrication technology to pit the template.

The second illustration provides more detail on this process, and shows the template in yellow, the growing bubbles in red and the polymer represented with a piece present (green) and the rest cut away to reveal the first three rows of expanding airbubbles.  In this illustration the pits are concealed by the rising bubbles, we show the process when the bubbles have already expanded out from the mouths of the pits.  The third row of bubbles to the right in this illustration more clearly shows how the growing air bubbles expand out into the polymer to form microbubbles, and specifically show the fully-expanded microbubbles provide inclusions in the polymer that, when the polymer is removed, will produce microbubble cavities in an array pattern, that is, an MBA™.

The end result is an array of microbubbles, for example as shown in the illustration to the left.  These microbubbles are very small (typically with a 50 uM diameter mouth and 100 uM in the largest diameter of the microbubble) with an extremely small volume (e.g., 1 nL).  A microbubble array typically consists of 10,000 or more microbubbles — our microscope slide sized arrays, for example, have about 70,000 microbubbles on them.

Commercial Applications

There are many applications for our MBA™s, not only based on our ability to reliably produce such large numbers of consistently dimensioned microbubbles with the patented GEM™ process, but also on the unique fluid-flow properties resulting from the bubble shapes.  Specifically, the shape of our microbubbles results in the contents being retained when the fluid outside the microbubble is circulating.  What this means in practice is that our microbubbles offer a superior environment for contents that are easily disturbed.

1. SUPERIOR CELL GROWTH FOR HIGH-THROUGHPUT SCREENING AND CANCER CELL STUDIES

One application Nidus has extensively pursued is the use of our MBA™s for superior cell growth.  A cell in a normal rectangular well won’t survive well because both the cell and the substances it secretes to condition its environment get washed away.  This effect is drastically reduced in our microbubbles; as a result we can grow single cells for days not just hours, an ability that directly translates to a superior platform for cell studies such as cell screens for antibody production.  The following illustration shows an artist’s rendering of cells deposited on the surface of one of our MBA™s, observe how some of the cells are settling into the microbubbles, where they will go on to grow:

The superior cellular growth environment our MBA™s provide is also directly applicable to cancer cell growth and formation of heterogeneously structured clumps of cells in a tumor.  Specifically, we’ve shown that cancer cells grow extremely well in our MBA™s and that these growing cells form tumor spheroids that have real potential for use as a better model system for tumor growth.

2. COMPOUND SENSING/TESTING

Nidus’s MBA™ technology can be used in many applications where repetitive testing occurs.  For example, each microbubble can be used as a nL-sized reaction chamber, and sets of microbubbles can be used as duplicate sets for different compounds.  The illustration below provides an abstracted representation of different compounds being tested in 9-up duplication (i.e., 9 replicate microbubble reactors per compound), each compound represented with a different color:

While these multiple reactions can be done manually without automation, Nidus has an elaborated development path to automated dispensing/reacting/assaying, which expands the broad applicability of this use of our MBA™ technology.

3. “BIOCHIP” APPLICATIONS

A “biochip” is a combined reaction array + sensor that allows for multiple biological interactions to be performed and sensed.  The idealized illustration below shows how our MBA™ technology can be used as the basis of superior biochips — the illustration shows a configuration where: the MBA™ is illuminated by a light source of appropriate light frequency or frequencies; a mirror is used both to direct the illumination down onto the array and then back up to a sensor; and, the sensor is used to analyze the reaction(s) occurring across the array and report the results out for further analysis and display:

The entire biochip market is expected to reach $18B by 2020; Nidus is vigorously developing its MBA™ technology for this market, and has strategic collaborators/partners to advance integration of our arrays with appropriate light/sensor packages for applications both in laboratories and in the field.

Nidus’s Credo

Nidus is committed to the commercialization of its patented GEM™ and MBA™ technologies for advanced cell growth methods and analytics; for repetitive reaction situations; and, for integration into biochips.  Our goal is not simply commercial success, but rather to significantly contribute to and advance methods in these fields.