CELLSCOPE: MOBILE MICROSCOPY FOR SINGLE CELL ANALYSIS

David N. Breslauer1, Robi N. Maamari1, Wilbur Lam2, Tom Hunt1, Luke P. Lee1, and Daniel A. Fletcher1

1Department of Bioengineering, UC Berkeley, Berkeley, CA, USA and 2Department of Pediatrics, UC San Francisco, San Francisco, CA, USA

ABSTRACT

We have developed a portable, wireless telecommunications-enabled optical microscope and cell analysis device. Based on a camera-enabled cell-phone, the sys-tem consists of a high-resolution microscopy attachment for the cell-phone and a microfluidic device for blood sample loading and staining. With this system, we have captured high-resolution images of healthy and diseased blood smears and demonstrated its utility for cell counting using a microfluidic device. This integrated cell-phone microscope and cell analysis device could be useful for monitoring cancer patient blood counts at home, with the patients able to capture and transmit images of their blood to their physician for consultation. KEYWORDS: microscopy, cell phone, cell counting, telemedicine

INTRODUCTION

Light microscopy is an essential tool in modern healthcare. Despite advances in diagnostic techniques and the development of lab-on-a-chip technologies, optical imaging of blood and tissue samples remains a vital and cost-effective technique for the diagnosis and screening of many diseases, ranging from leukemia to sickle cell disease to malaria. However, conventional light microscopes are large instruments that typically remain confined to well-equipped healthcare clinics. We have devel-oped a portable, high-resolution microscope attachment for camera-enabled cell phones, dubbed the CellScope (Figure 1) that can be used to extend the reach of light microscopy in modern healthcare.

Figure 1. (A) Handheld CellScope. A sample stage, holding the microfluidic de-

vice, is attached to a focusing wheel. (B,C,D) Microfluidic devices for cell sample preparation. (B) Device to load samples into viewing chambers. (C) Device to mix a

sample with a stain and load into chambers. (D) Device to mix sample with two stains in parallel, and load them into chambers.

978-0-9798064-1-4/µTAS2008/$20©2008CBMS 456

Twelfth International Conference on Miniaturized Systems for Chemistry and Life SciencesOctober 12 - 16, 2008, San Diego, California, USA

To fully exploit the potential of a handheld light microscopy system, we are de-

veloping microfluidic devices that load and prepare patient samples, such as blood, within chambers matched to the field of view obtained with the CellScope optics (Figure 1). In contrast to conventional blood smears using slides, the microfluidic devices prepare samples can be easily and rapidly visualized and analyzed.

Taking advantage of the expanding wireless infrastructure around the globe, the CellScope will enable healthcare workers in remote regions to take images of pa-tients’ samples and wirelessly transmit those images to clinical experts who can ev-aluate them and respond with a diagnosis and treatment recommendation. OPTICAL SYSTEM CHARACTERIZATION

The current CellScope magnifying lens system attaches to a standard camera-enabled cell phone (Nokia N73 with 3.2 megapixel camera). The device is designed to use standard coupling lenses and microscope objectives, such that magnification can be adjusted by attaching different magnification objectives. For this study, our system has a magnification comparable to that obtained with a 50X objective on a conventional light microscope, with a field-of-view width of 195 µm. As seen from edge response curve of a 100 line/mm grating (Figure 2), images taken with the cur-rent system are affected by chromatic aberration and pincushion distortion. We an-ticipate overcoming these optical distortions through the development of a custom lens design.

With this resolution, we have been able to use the CellScope to capture high quality images of cell samples (Figure 3) and make reliable measurements of cell density (Figure 4).

MICROFLUIDIC SAMPLE PREPARATION

We have developed a hemocytometer-like device that can load a sample of cells by capillary action (requiring no pumps) into four chambers, using less than 20µL of sample (Figure 2). These chambers are the size of the CellScope field-of-view (Fig-ure 4) and are arranged such that the device can be translated along one axis to en-able rapid image capture of multiple fields-of-view.

We have validated the ability of the CellScope to be used for cell counting by comparing cell counts obtained using a standard hemocytometer laboratory micro-scope with the the CellScope and microfluidic device (Figure 4). We found that cell counting can be reliably performed using the CellScope with both manual and auto-

Figure 2. Edge response curve used to measure image resolution/sharpness. Data

from 50X magnification. Conversion scale is 8.8pixels/µm.

457

Twelfth International Conference on Miniaturized Systems for Chemistry and Life SciencesOctober 12 - 16, 2008, San Diego, California, USA

mated counting methods. However, the performance of automatic counting is slightly diminished on the CellScope due to reduce image contrast as compared to a conventional laboratory microscope. Further development of the microfluidic de-vices will enable loading, staining, and fixing cells over a hemocytometer grid for an extended range of applications.

CONCLUDING REMARKS

Combinations of microfluidic devices with mobile wireless technology have the potential to have a high impact on global health care technology, particularly in the developing world and rural areas where laboratory facilities are scarce but cell phone infrastructure is extensive. By using existing communication infrastructure and ex-panding the capability of existing cell phone technology– rather than developing a separate device– the CellScope will enable greater access to high quality health care by allowing rapid microscopic evaluation of patient samples away from the clinic.

ACKNOWLEDGEMENTS

We thank Tanner Nevill, Erik Douglas and Michael Rosenbluth for helpful dis-cussions. The authors acknowledge the Blum Center for Developing Economies, CITRIS, and Microsoft Research for funding.

Figure 3. Microfluidic chamber loaded with HeLa cells. (Left) Picture of chamber taken with a standard inverted microscope. (Right) Picture of the same chamber

taken with CellScope. Taken at 20X magnification. Scale bars are 100µm.

Figure 4. Evaluation of cell counting with the microfluidic sample preparation

device on the CellScope. (n=4, p=0.84 for manual counting between the hemocy-tometer and the CellScope, p=0.23 for ImageJ counting between the hemocy-

tometer and the CellScope)

458

Twelfth International Conference on Miniaturized Systems for Chemistry and Life SciencesOctober 12 - 16, 2008, San Diego, California, USA