Tiny Mobile Phone Microscope

Ozcan tiny microscope for cell phone
The prototype for the lensless microscope developed at UCLA has the approximate diameter of a US Quarter. The microscope only weighs 46 grams, about as much as a large egg. (Courtesy of Ozcan Research Group @ UCLA)

My niece has worked in remote developing nations, in places like a tiny village in South Africa where the women have to walk several hours to fetch clean water. In order to travel to such areas, she had to take malaria medication and get a lot of vaccines — such as hepatitis A and B, yellow fever, typhoid, rabies, rubella, and diphtheria vaccines. HIV and Aids can also be prevalent. Unfortunately medical care and resources are often very limited in such isolated villages, where a doctor is many miles away and the villagers may not have access to vehicles or proper roads. To address this critical need, people are using new technology to bring the patients figuratively to the doctors. For example, medical data is acquired and then transmitted to a doctor or medical specialist elsewhere for offline assessment.

This field of telemedicine is growing rapidly. Some telemedical technology relies on the fact that cell phones are now used even in the developing world, as evidenced by extensive cell phone use after the recent earthquake in Haiti. Wireless phone technology has become significantly cheaper and the technical capabilities of cell phones is rapidly improving.

Aydrogan Ozcan, a research engineer at UCLA, has created a tiny microscope that is portable and lensless for telemedicine applications. The microscope attaches using a USB connection to a smart-phone, PDA or computer. This week his group published a paper describing in detail his latest, tiniest microscope. This minature microscope weighs just 46 grams (about the same weight as a large egg) and has dimensions of about 4 cm x 4 cm x 6 cm. It can image sub-cellular structures (with 1-2 micron resolution) over a 24 mm2 imaging area.

Microscopes normally use a lens to magnify the image of an object, where the image is generated by an electromagnetic (in optical microscopes) or electron (in electron microscopes) beam passing through the sample. However, standard microscopes are bulky and expensive, so they are generally used only in laboratories.

Ozcan’s lensless miniature microscope is instead based on digital in-line holography. It uses a simple light-emitting-diode (LED) and a compact digital sensor array to capture holographic images of blood samples or other fluids. A small chip is filled with a fluid sample, such as a blood smear, that is inserted into the microscope. The LED passes incoherent light through the sample, and the interference of the light waves that pass through the cells creates a hologram of each cell. The microscope digitally records these holograms, then rapidly reconstructs images of the cells. A compressed version of each holographic image can then be transmitted to hospitals elsewhere using wireless cellular networks, which have penetrated even the most remote corners of the world.

This portable microscope can accurately identify and count cells, including red blood cells, white blood cells, platelets, and T-cells (white blood cells whose counts are important for accurate diagnosis of AIDS). So this technology could help monitor diseases like malaria, HIV, and tuberculosis. It could also be used to test water quality following a disaster, such as a major earthquake or hurricane.

Ozcan’s microscope is also durable and easy to use. You just need to fill a chip with a sample and slide the chip into the slot in the microscope. The sample doesn’t need to be perfectly aligned in the microscope, so very minimal training is needed. It also uses cheap parts and a standard smart-phone. Plus the images are analyzed automatically by a computer, instead of requiring a trained medical technician.  However, this analysis does have a potential down-side. Namely, the computer automatically identifies a cell by comparing the cell’s hologram to a cell hologram library, but I’ve seen little information on the development of this database.

Overall though this new tiny mobile phone microscope has great promise. It could become a very cost-effective tool for telemedicine applications. Next time my niece heads off to a remote village, maybe she can have a tiny microscope to attach to her smart-phone just in case?

Advertisements

Science At The Theater

I want to let my Bay Area readers know about an upcoming cool science lecture for the general public. Berkeley Lab presents “Just Say No To Carbon Emissions” on April 26 from 7-9 pm at the Berkeley Repertory Theatre. Admission is free. There will be three dynamic speakers from Berkeley Labs discussing renewable energy topics. Ramamoorthy Ramesh, a material scientist, will describe current research efforts to make cheap solar. Nan Zhou will discuss efforts to increase energy efficiency and reduce carbon dioxide emissions in China. Lastly, the geologist Curt Oldenbury will explain a strategy to reduce carbon emissions from coal and natural gas, by storing it deep underground. This event is co-sponsored by “Friends of Berkeley Lab” and “Berkeley Energy and Resources Collaboration.” For more information, check out their website.

Hope for Alzheimer’s Patients?

PET image of brain using PIB
Courtesy of Dr. Jagust Lab, UC Berkeley

My mother died of Alzheimer’s at the age of 69, so I can personally attest to the horror of this disease. I can think of few things worse than slowly watching your cognitive abilities decline, particularly if you are aware of the progressive deterioration as my mother was. So I’m keeping a close watch on the latest Alzheimer’s research, including the research of my colleague William Jagust who is a neuroscientist at UC Berkeley.

Dr. Jagust is participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which is large multicenter project supported by NIH, private pharmaceutical companies and nonprofit organizations. The primary goal of ADNI is to discover indicators (biomarkers) that can track disease progression and hopefully diagnose Alzheimer’s early on. Basically, they want to help speed up and streamline drug and clinical trials by developing biomarkers that track Alzheimer’s more reliably.

The initial ADNI five-year research project completed last fall. It studied cognition, function, brain structure and biomarkers for 800 subjects (200 elderly controls, 400 subjects with mild cognitive impairment, and 200 subjects with Alzheimer’s). The clinical data from the patients went into a large database, including MRI scans, PET scans, blood tests, neuropsychological tests, and genetic tests. The truly unique thing is that this database can be accessed by the public through a website. Basically the raw data (with patient personal information removed) is made available for everyone to use, in hopes that this will help scientists more rapidly understand and treat Alzheimer’s. This ADNI project just received the second phase of funding, so the studies will be expanded.

Although the cause and progression of Alzheimer’s disease is not fully understood, current research indicates that the disease is associated with the formation of “amyloid plaques” and “neurofibrillary tangles” in the brain that damage nerve cells. What does this mean? Amyloid plaques are protein fragments that the body produces naturally. In a healthy brain, these protein fragments are broken down and eliminated. In a brain with Alzheimer’s, the fragments instead accumulate to form hard, insoluble plaques between nerve cells. This excess amyloid buildup occurs before clinical Alzheimer’s symptoms, so it may be used as a predictor of disease. Neurofibrillary tangles are insoluble twisted fibers found inside the brain’s cells. These  tangles mainly consist of a protein called tau, which helps form microtubules that transport nutrients from one part of the nerve cell to another. In an Alzheimer’s brain, the tau protein is abnormal and the tangles collapse this important transport system.

Dr. Jagust and other researchers are studying this beta-amyloid buildup using medical imaging, including PET imaging with a new drug called [11C]Pittsburg Compound B. This new PET drug binds to beta-amyloid plaques and indicates their size and position. “With PET, we’re able to study the biochemistry of the brain, and with MRI we can study both the anatomy and structure of the brain,” Jagust said. “We can also study some of the function of the brain to see what parts of the brain are active during different cognitive tests. So when you put all this information together, you can get a very detailed picture of how the brain is functioning and how function and structure might change with age.” Last fall Jagust published an article on the relationships between biomarkers in aging and dementia. The group found that the confluence of three factors — beta-amyloid deposition, atrophy of the hippocampus (part of the brain that stores and sorts memories), and episodic memory loss — signals early stage of Alzheimer’s. Hopefully this new understanding will ultimately provide early and more accurate diagnosis.

I don’t have room here to summarize all the results from the Jagust lab, let alone all the other labs doing Alzheimer’s research. But I must say that I’m optimistic given the recent progress they have made in understanding the disease. There are also many clinical trials underway for new Alzheimer’s drugs, including ones that hope to stop cognitive deterioration instead of just reducing symptoms. I’m encouraged but I still tell my friends who are doing the research that they need to find a cure within the next 10 years, because I do not want to suffer through this frightening disease like my mother did.

PET Imaging — Not for Cats or Dogs

PET ring drawingAs a medical imaging researcher, I notice when medical imaging technologies are mentioned by popular news media or medical-themed television shows. Lately I’ve been seeing PET imaging mentioned more frequently, including on TV shows like House and Grey’s Anatomy. This probably just reflects the fact that dramatically increasing numbers of PET scans are being performed in real life in clinics and hospitals. So what is PET imaging? Funny that you ask, because I just happen to do research in this field.

In this context, PET stands for Positron Emission Tomography. During a PET scan, a trace amount of biologically-active, radioactive drug is injected into the patient’s vein. The drug localizes somewhere in the patient, depending on the metabolic properties of the selected drug. The drug then emits a positron (anti-particle of the electron), and the positron annihilates with an electron in the patient’s body. The resulting energy forms gamma ray pairs that pass through the patient and are detected by the PET scanner. These detected gamma ray signals are used to create a 3-D volumetric image or picture of the drug’s concentration in the body.

PET imaging technology is unique because it images a patient’s metabolism, whereas most other medical imaging techniques measure anatomical structure. For example, X-ray CT or MRI scans can be used to identify a tumor because they show the patient’s anatomy in detail. However, PET imaging can identify if the tumor is benign or cancerous, by measuring whether or not the tumor takes up the radioactive drug. In reality, you’d really like to know both though — detailed anatomical structure and metabolic function. Recent work has demonstrated the increased clinical diagnostic value of fusing imaging technologies based on function (e.g., PET, SPECT or functional MRI) with those based on structure (e.g., CT, MRI, or ultrasound). As a result, PET and CT scanners are now typically combined into a single gantry system, so that images can be taken from both devices sequentially during a single procedure.

Since PET measures metabolism instead of anatomical structure, it is mostly used to image organs whose size or shape does not indicate whether they are functioning properly, such as the brain or heart. It is also used to diagnose diseases that exhibit an abnormal metabolism, such as cancer.

Stay tuned this week when I discuss some Alzheimer’s research that utilizes PET imaging.