Pocket Pathology

No more than a hobby in the 17th century, microscopy has transformed over the last few centuries into an ever-growing industry that is forecast to be worth nearly $4 billion by 2017 (1). While the optical technology behind light microscopy has seen little change over the last few years, the digital revolution has not left pathologists behind. Modern imaging technology has taken a quantum leap – nowadays, miniature digital cameras like those found in smartphones are outperforming even dedicated digital compact cameras. Knowing this, it seems inevitable that smartphone cameras will emerge as a new microscopy imaging platform.

A low-cost mobile microscope with a small form factor is pivotal to myriad existing practices not just in medicine, but also in agriculture, geology, ecology and marine biology. In essence, having technology like this means that samples can be examined at microscopic levels and shared from anywhere in the world on a real-time basis, thanks to Internet connectivity. For pathologists, a disposable microscope in your pocket opens up the possibility of making diagnoses “on the go.” It’s useful in all sorts of situations – for instance, medical practitioners in developing countries can bring the microscope along with them when they go to work. For laboratory-based pathologists, it allows you to have multiple digital automated microscope systems, which can increase the number of tests that can be completed and diagnoses made. The advent of these small, portable microscopes has drawn significant interest from the commercial, medical and scientific worlds, but they all share a fundamental technological and economic barrier – the imaging lenses. Imaging lenses are produced by grinding small pieces of glass or casting molten plastic in molds, processes that require specialized equipment. By re-examining the lens-making process, we break down the barriers and gain access to high-resolution imaging for mobile microscopy.

Droplet lenses: nature’s design

Nature makes lenses with droplets on a daily basis. Dew forms through the process of condensation, where miniscule drops of water nucleate and coalesce to form millimeter-sized water droplets (“macrodroplets”) on a solid surface. These droplets of clear liquid can bend light, acting as lenses. We exploited this well-known phenomenon to develop a new process for creating inexpensive, high-quality lenses.

To begin with, we developed elastomer lenses that, when combined with a standard smartphone camera, can resolve images down to four micrometers. Because the lenses are formed using naturally occurring forces – surface tension and gravity – the cost of production is a mere penny, spent on the materials themselves. So far, we’ve made lenses a few millimeters thick that have a maximum magnification power of 160 times and a resolution of about four microns – which is about two times lower than the average commercial microscope, but costs over three orders of magnitude less to produce (2). The surprise for us was the level of magnification enhancement we were able to achieve using a very simple lens production process.

All we need is an oven, a glass microscope slide and a common, gel-like silicone polymer called polydimethylsiloxane (PDMS). First, we drop a small amount of PDMS onto the slide and bake it at 70 degrees Celsius for 15 minutes to harden it, creating a base. Then, we drop another dollop of PDMS onto the base and flip the slide over. Gravity pulls the new droplet down into a parabolic shape. We bake the droplet again to solidify the lens, after which we can add more drops as needed to hone the shape of the lens and increase its imaging quality. Current methods of making lenses are difficult and expensive because of the need for specialty lathe or molding equipment (3). Our new method allows us to harvest solid lenses of varying focal lengths just by hanging and curing droplets of different volumes – an easy and inexpensive recipe!

How it works

The lens is designed to be placed directly onto the back of a smartphone camera (Figure 1, left) to take magnified images of samples under ambient light. We’ve also developed a 3D-printed lighting unit with two mini-LEDs (Figure 1, middle and right), which can be fitted onto the smartphone if better illumination is needed. Even with the lighting unit included, the attachment is more than two times smaller and slimmer than any existing ones – an advance that led me to release its design at Google’s recent “Mobile First World” conference, which focused on the global transition from an Internet-based lifestyle to a mobile-based one.

When used as a standard light microscope, our device resolves structures down to four micrometers in transmission lighting with a five-megapixel camera. This is about two times lower than the resolution a polymer lens can achieve (Figure 2, top). But for dermatoscopy applications, our lenses have very good optical performance on skin (Figure 2, bottom). At the moment, the elastomer lens is interesting commercial parties in the area of skin diagnosis, and the technology can be extended to imaging devices in other primary care fields like otoscopy, ophthalmology and even endoscopy.

Moving to mobile microscopy

Why is it worth using this technology yourself? Cost provides a compelling argument. Mobile microscopes reduce the startup costs involved in creating new pathology services, so that pathologists can begin working in more remote areas without spending more than necessary. With the advent of different mobile health networks, smartphone-enabled microscopes and other tools can be linked to cloud services where patient data are stored and shared among medical professionals through secured networks. The first challenge to overcome, though, is to get pathologists and clinicians to begin adapting their practices to mobile microscopy. Though it’s an ideal tool for use in developing countries, most high-resolution smartphones are still fairly expensive, and medical practices in those countries often follow very traditional practices. I think that once first-world countries begin to use mobile microscopes in their clinics, it’ll start trickling down to developing countries, where we’ll see wider adoption.

At the moment, I feel like pathologists are still waiting to see how this kind of technology will pan out. I know that one of the key issues to overcome in mobile microscopy is to capture a high-resolution image (micrometers) over a large area (centimeters) very quickly, so that rapid diagnoses can be carried out on suspicious tissue. Having this access on a portable device gives pathologists their ideal pathology microscope in a pocket. Mobile microscopes still have a limited field of view, but I anticipate that this concern will eventually be addressed by a combination of more powerful smartphones, inexpensive optics, and better computational processing of optical images. People also like to have different microscope imaging setups (like fluorescence, darkfield, or phase contrast) available in different modules for their smartphones, so expanding the available options might increase the rate of adoption.

A pathology game-changer

I anticipate that we’ll develop more and more applications for mobile microscopy, and as we continue to expand what we can do with the technology, it will become more and more popular. My team has recently discovered, for instance, that we can use simple capillary effects to create concave lenses, which can be combined with convex lenses to reduce aberrations and pave the way to creating disposable endoscopy systems based on elastomer lens technology. Another interesting direction we can take is into flatbed scanning – we’ve already seen the success of flatbed scanners for digital pathology, as they’ve been widely adopted in major hospitals. In the future, I hope we’ll see a dedicated miniature flatbed scanner, based on smartphone technology, in every pathologist’s pocket. Once they can start performing flatbed scanning with a system that fits in a pocket, I think mobile imaging technology will become a game-changer for pathology practices. With the almost exponential increase in imaging chip resolution, this could happen within the next five years.

You could say that Antonie van Leeuwenhoek, an unremarkable tradesman, laid a new cornerstone in science by using a homemade high-powered lens to reveal a whole new world beyond our naïve vision. As a result of this discovery and his ingenuity, he gave birth to the field of microbiology through single-lens microscopy. Now, we are moving into an era when every individual can have the microscopic world right at their fingertips – and that includes pathologists, who may one day soon be able to take their laboratories with them wherever they go.