In Vitro Diagnostics

Laser micromachined interconnect in a polymer-based micro-fluidic chip

Microfluidic Chip

The trend towards low-cost, polymer-based disposables for in vitro diagnostics and point-of-care testing requires systems to screen and collect cells, as well as miniature electrical circuits to detect and amplify signals. Highly precise laser technology, especially laser drilling, is an attractive manufacturing method to meet the feature sizes and tolerances at the cellular level.

Laser Micromachining for Various Diagnostic Areas

Laser micromachining is used to fabricate consumable sensors in multiple areas within the diagnostics device industry. These include cytology, flow cytometry, molecular and cancer diagnostics.

Because laser micro-machining can drill a hole as small as 2 microns in diameter, lasers are ideal tools to drill precise holes in polymer-based micro-fluidic chips to isolate individual cells such as white blood cells, cancer cells or to change the cell chemistry. Similar to the cellular phone industry, lasers are also used to drill small interconnects and upstream filters.

0.5 micron lines and spacers in polymer film

0.5 micron lines and spacers in polymer film

Cytology

Cytology involves the study of cell structures, cell composition and cell interaction. The concentration of bacteria, viruses and other pathogens in blood can help assess the state of an infectious disease or the success of an immune system's reaction.

Laser technology helps in the manufacture of low cost, portable automated cell counters based upon the Coulter counter principle.   A laser drills the critical hole where a single cell passes through a pair of electrodes. The cell's passage instantaneously increases resistance between electrodes, which indicates cell count and cell volume.

Flow Cytometers

Flow cytometers are sophisticated cell counters that can also analyze internal structures, protein levels and biochemistry. Like most instruments, there is a trend to replace bulky table-top flow cytometers with handheld portable devices where a small semiconductor laser interrogates the cell passing through a laser-drilled hole. The semiconductor laser is pointed at a cell stream tagged with a fluorescent reagent, and the reflected and transmitted light and fluorescence signals are detected. In these applications, lasers are used both as a component of the device and a method of fabrication.

Molecular Diagnostics

Molecular diagnostics identifies genetic or protein activity patterns to determine the presence of infectious and genetic diseases, as well as to identify the types of antigens attacking the host. The measurement of genetic content (DNA, RNA, proteins, metabolites), including DNA sequencing, may help physicians understand the probability of a patient developing a disease or whether a specific treatment will work. The discovery of new genes and biomarkers accelerates the development of new clinical tests.

Miniature bioreactor

Miniature Bioreactor

Lasers can be used to drill miniature bioreactors to greatly increase the throughput or to combine multiple tests together for “panel” testing. Lasers are ideal for drilling larger arrays (thousands) of blind wells in relatively non-fluorescent polymers as small as 2 microns in diameter and depth. Polymer-based miniature bioreactors can be implemented, for example, in technology platforms for digital PCR, next generation DNA sequencing and infectious disease diagnostic assays.

Oncology Diagnostics

Cancer diagnostics tools can look at the signal transduction at the cellular level to identify specific markers that help physicians decide on a course of action. Laser drilling, with its precision to create holes at the cellular level, can assist in the challenging collection of live tumors.

Collection of blood to analyze circulating tumor cells (CTCs) is another approach where the detection of fragments from the tumor offers both prognostic and diagnostic applications. Lasers can be used for fabrication of electrical via connections or filters in the disposable chips.